New parameters for identifying subclinical atherosclerosis in patients with primary Sjögren's syndrome: a pilot study.

OBJECTIVES: We investigated sub-clinical cardiovascular involvement in primary Sjögren's syndrome (pSS) patients by means of ADMA, coronary flow reserve (CFR), intima media thickness (cIMT), pulse wave velocity (PWV) and myocardial deformation. METHODS: The study involved 22 outpatients with pSS (6 males, 16 females; mean age 60.14±7.81 years) and no documentable cardiovascular disease, and 22 age- and gender-matched controls. Dipyridamole transthoracic stress echocardiography was used to evaluate wall motion and CFR. A CFR value of <2.5 was considered a sign of impaired coronary function. We also evaluated cIMT arterial stiffness PWV and plasma ADMA levels, and made a speckle tracking echocardiography (STE) analysis. RESULTS: All of the patients were affected by pSS. Although within the normal range, the patients' CFR was lower than that of the controls (median 2.70; IQR 2.40-2.90 vs. 3.20; IQR 3.06-3.33; p<0.0001), whereas their ADMA levels were significantly higher (median 0.81 µM; IQR 0.79-0.85 µM vs. 0.54 µM; IQR 0.52-0.58 µM; p<0.0001). Both left and right PWV values were significantly higher in the patients than in the controls (median 8.8 m/s right and 8.9 m/s left vs. 6.86 and 6.89 m/s), whereas QIMT was substantially similar in the two groups. CONCLUSIONS: Higher ADMA levels suggest the presence of endothelial dysfunction and sub-clinical atherosclerosis in pSS patients, even in the case of a normal CFR. This finding is supported by the PWV values, which were higher in the pSS patients. ADMA levels and PWV values may be useful markers for identifying early endothelial dysfunction in pSS patients.

Cardiovascular involvement in psoriatic arthritis.

Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA), although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD) risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA). Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules), autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA) levels were significantly high and coronary flow reserve (CFR) was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.

[Cardiac involvement in rheumatoid arthritis]. / Il coinvolgimento cardiaco nell'artrite reumatoide.

Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It's an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non-Hodgkin lymphoma). Among extra-articular complications, cardiovascular (CV) involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.

Nearly automated analysis of coronary Doppler flow velocity from transthoracic ultrasound images: validation with manual tracings.

Coronary flow velocity reserve is obtained by manual tracings of transthoracic coronary Doppler flow velocity profiles as the ratio of stress versus baseline diastolic peak velocities. This approach introduces subjectivity in the measurements and limits the information which could be exploited from the Doppler velocity profile. Accordingly, our goals were to develop a technique for nearly automated detection of Doppler coronary flow velocity profile, and automatically compute both conventional and additional amplitude, derivative and temporal parameters, and validate it with manual tracings. A total of 100 patients (17 normals, 15 patients with severe coronary stenosis, 41 with connective tissue disease and 27 with diabetes mellitus) were studied. Linear correlation and Bland-Altman analyses showed that the proposed method was highly accurate and repeatable compared to the manual measurements. Comparison between groups evidenced significant differences in some of the automated parameters, thus representing potentially additional indices useful for the noninvasive diagnosis of microcirculatory or coronary artery disease.

Cardiovascular and autoimmune diseases in females: The role of microvasculature and dysfunctional endothelium.

Cardiovascular (CV) diseases are becoming increasingly frequent and associated with a high incidence of CV events, disability and death. It is known that there is a relationship between CV burden and systemic autoimmune diseases (SADs) that is mainly due to inflammation and autoimmunity, but the other mechanisms underlying the high CV risk of SAD patients have not yet been fully clarified. The aim of this review article is to discuss some of the specific factors associated with the accelerated atherosclerosis (ATS) characterising SADs (female sex, the microcirculation and the endothelium) in order to highlight the importance of an early diagnosis and the prompt implementation of preventive measures, as well as the possible role of new therapeutic strategies such as vaccine immunomodulation. Finally, as the natural history of ATS begins with endothelial injury (a potentially reversible process that is influenced by various factors) and microvascular damage plays a central role in the etiopathogenesis of SADs, it underlines the crucial need for the development of reliable means of detecting sub-clinical abnormalities in the microcirculation, particularly coronary microcirculation dysfunction.

Effects of an inhaled bronchodilator on gas distribution and over-all ventilatory efficiency in patients with chronic obstructive pulmonary disease.

The effects of an inhaled bronchodilator on the distribution of inspired gas and over-all efficiency of ventilation were studied by the nitrogen washout technic in 16 patients with chronic obstructive pulmonary disease; three normal subjects and two patients with asymptomatic asthma (and normal spirometric values) were also studied. In normal and asthmatic subjects and in patients with chronic obstructive pulmonary disease and mild to moderate functional impairment, the nitrogen clearance did not vary significantly or showed changes suggesting less uniform gas distribution and reduced ventilatory efficiency. In most patients with advanced chronic obstructive pulmonary disease, the bronchodilator caused changes suggesting more uniform distribution of inspired gas and increased efficiency of ventilation. Multiple regression analysis showed that the behavior of the nitrogen clearance after treatment was also related to the response of the anatomic dead space. The effects of the bronchodilator varied with time. The results are consistent with the assumption that the changes in nitrogen clearance after bronchodilator therapy reflect the concourse of multiple factors, which may be expected to have favorable or unfavorable effects on the distribution of inspired gas and the efficiency of ventilation.

Pain threshold and tolerance in women with syndrome X and women with stable angina pectoris.

A recent report showed that during Holter monitoring of patients with syndrome X (typical anginal pain, positive exercise test response [at least 0.1 mV of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries), 50% of episodes of ischemic ST-segment depression were painful. This proportion is considerably higher than that in patients with chronic stable angina, which is about 30%. A significantly lower threshold and tolerance to painful stimuli was seen in a group of patients with chronic stable angina in whom 50% of episodes were painful compared with a group in whom only 5% of episodes were silent. Hence, patients with syndrome X may have enhanced sensitivity to painful stimuli. To investigate whether this difference was due to a lower threshold for painful stimuli in general, 12 patients with syndrome X and 10 (age- and sex-matched) with chronic stable angina were studied using the same battery of painful stimuli. Patients with syndrome X had a significantly lower threshold and tolerance for forearm ischemia (-36%, p less than 0.05, and -40%, p less than 0.001) and electrical skin stimulation (-37%, p less than 0.01, and -35%, p less than 0.001); the cold pressor test did not show significant differences (-7%, p = 0.391, and -1%, p = 0.818). Thus, patients with syndrome X in this study had significantly lower threshold and tolerance values for forearm ischemia and for electrical skin stimulation. These differences in sensitivity to pain may partly explain a higher incidence of painful ischemic episodes detected by ambulatory electrocardiographic monitoring during unrestricted daily life.

Validation of an Italian version of the Fibromyalgia Impact Questionnaire (FIQ-I).

OBJECTIVE: To validate a translated Italian version of the Fibromyalgia Impact Questionnaire (FIQ). METHODS: The Italian version of the FIQ was administered to 50 patients affected by fibromyalgia (FM) (48 patients filled out the questionnaire again 10 days later) together with the Italian version of the Stanford Health Assessment Questionnaire (HAQ), the Medical Outcomes Survey Short Form-36 (SF-36), and a tender point count (TPC) obtained by summing the score (0-3) of each tender point tested by thumb palpation. All patients were asked about the severity of pain today (10 cm visual analog scale) and the duration of symptoms. Test-retest reliability was assessed using Spearman correlations. Internal consistency was evaluated with Cronbach's alpha of reliability. Construct validity of the FIQ was evaluated by correlations between the HAQ and subscales of the SF-36 as well as the TPC. RESULTS: The mean duration of symptoms was 6.5 years and the mean age of the participants was 57.4 years. Test-retest reliability was between 0.74 and 0.95 for physical functioning as well as for the total FIQ and other components. Internal consistency was 0.90 for the overall FIQ. Significant correlations were obtained between the FIQ items, the HAQ and the SF-36. CONCLUSIONS: The Italian FIQ is a reliable and valid instrument for detecting and measuring functional disability and health status in Italian patients with FM.

Hypersomnolence in fibromyalgia syndrome.

OBJECTIVE: To evaluate hypersomnolence in patients affected by fibromyalgia syndrome. METHODS: Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) completed a sleep questionnaire and underwent the following evaluations: lung function tests; polysomnography; the Epworth sleepiness scale (ESS), which measures sleep complaints and daytime hypersomnolence; and the visual analogical scale (VAS) to detect subjective pain, fatigue, anxiety and depression. RESULTS: The FMS patients were divided into two groups based on their ESS score. Patients complaining of daytime hypersomnolence had a higher number of tender points (15 +/- 2 vs. 12 +/- 1, p < 0.01), a higher subjective pain score (72 +/- 15 vs. 52 +/- 13, p < 0.05), and more fatigue (p < 0.05). The diffusing capacity of the lung (Tlco) was more impaired and the occurrence of periodic breathing was higher. FMS patients complaining of daytime somnolence had significantly less efficient sleep than the FMS patients with no daytime somnolence (p < 0.05), i.e. a lower proportion of stage 3 sleep (5 +/- 2% vs. 12 +/- 3%; p < 0.001), stage 4 sleep (1 +/- 0.5% vs. 4 +/- 1%; p < 0.001), and twice as many arousals per hour of sleep (p < 0.01). The respiratory pattern of FMS patients with hypersomnolence showed a higher occurrence of periodic breathing (p < 0.05). The short length of apneas and hypopnoeas did not affect the apnea/hypopnea index (5.1 +/- 3 vs. 7 +/- 4; ns), but FMS patients with daytime hypersomnolence had a greater number of desaturations per hour of sleep (11 +/- 6 vs. 6 +/- 5; p < 0.05). Pulmonary volumes did not differ between the two groups. The EES score was significantly correlated in FMS patients, and even more markedly in the FMS patients with hypersomnolence, TLco, A/I, and disease duration. The ESS score was correlated significantly with the number of tender points only in FMS patients with daytime hypersomnolence. CONCLUSION: The occurrence of daytime hypersomnolence in FMS patients is linked to a greater severity of fibromyalgia symptoms and to more severe polysomnographic alterations.

The Italian version of the Fibrofatigue Scale, a reliable tool for the evaluation of fibromyalgia symptoms.

OBJECTIVE: To validate a translated Italian version of the Fibrofatigue Scale (FFS). METHODS: The Italian version of FFS was administered to 60 patients affected by fibromyalgia (FM) (57 patients were interviewed again 10 days later) together with the Italian version of the Fibromyalgia Impact Questionnaire (FIQ), the Stanford Health Assessment Questionnaire (HAQ) and the Medical Outcome Survey Short Form-36 (SF-36). All patients were asked about the severity of pain today (10-cm visual analogue scale) and the duration of symptoms. Test-retest reliability was assessed using Spearman correlations. Internal consistency was evaluated with Cronbach's alpha of reliability. Construct validity of the FFS was evaluated by correlations among the FFS, the FIQ and the subscales of the SF-36. RESULTS: Mean duration of symptoms was 7.6 years, and mean age of participants was 56.3 years. Test-retest reliability was between 0.70 and 0.95 for the single items as well as for the total FFS and other components. Internal consistency was 0.90 for the overall FFS. Significant correlations were obtained between the FFS items and the SF-36. CONCLUSIONS: The Italian FFS is a reliable and valid instrument for detecting and measuring functional disability and symptoms severity in Italian patients with FM.

Evaluation of respiratory influences on left ventricular function parameters extracted from echocardiographic acoustic quantification.

This study was designed to assess, using the echocardiographic acoustic quantification technique, the influence of respiration on left ventricular (LV) function and its modifications connected with the ageing process, quantifying in a non-invasive way the respiratory contribution to the LV volume variability. An automated algorithm is applied to extract the beat-to-beat measurements of LV function parameters from the LV volume signal, obtained from recordings lasting a few minutes. Mean values, amount of variability and spectral content were studied in a population of 17 normal young (mean age 25 +/- 1 years) and 12 normal old (mean age 64 +/- 2 years) subjects. Mean values of the beat-to-beat measurements of LV function parameters were able to point out alterations connected with the ageing process in peak filling rate, peak atrial filling rate and peak ejection rate. Spectral analysis, applied to the extracted variability series, displayed a predominance of the high-frequency (HF) component corresponding to respiration in all LV function parameters; moreover, age related changes of HF variability were observed in peak ejection rate. The HF power spectrum component of beat to beat series extracted from the LV signal can provide a non-invasive assessment of the fluctuations in ventricular parameters associated with respiration.

Analysis of cardiac left-ventricular volume based on time warping averaging.

The cardiac left-ventricular (LV) volume signal, obtained by acoustic quantification, is affected by noise and respiratory modulation, resulting in a large beat-to-beat variability that affects the computation of LV function indices. A new method is proposed to improve the evaluation of LV indices by applying a signal averaging technique based on dynamic time warping to consecutive LV volume waveforms. Volume signals obtained from ten normal young (NY) subjects (mean age +/- SD: 25+/-5 years) were used to evaluate the performance of this algorithm. To evaluate its clinical utility, the effects of ageing and pharmacologically induced changes on LV function were assessed by studying, respectively, ten normal (N) adult subjects (age 64+/-8 years) and ten patients with dilated cardiomyopathy during a control and low-dose dobutamine (10 microg kg(-1) min(-1)) study. Indices of LV function were highly consistent, with a variability of less than 8%, even when only 16 beats were averaged, independently of their selection inside the whole recording. When compared with beat-to-beat measures, the averaging of 16 beats significantly reduced (by more than 50%) the interbeat variability of all indexes. Expected alterations in both diastolic and systolic function were evidenced both with ageing (peak filling atrial contraction and ejection rates: from 275+/-77 mls(-1), 76+/-30 ml s(-1) 230+/-70 mls(-1), respectively, in NY, to 160+/-33 mls(-1), 125+/-39 mls(-1), 163+/-54 mls(-1) in N) and with dobutamine (peak filling and ejection rates from 160+/-72 mls(-1) and 183+/-86 mls(-1) respectively, in control, to 253+/-75 mls(-1) and 251+/-105 mls(-1) with dobutamine). Signal averaging with time warping allows fast and improved assessment of LV function.

A case of subannular aortic aneurysm detected by transoesophageal echocardiography.

Subvalvular aortic aneurysm is a cardiac abnormality extremely uncommon in white adult patients. Accurate diagnosis can be made by transoesophageal echocardiography which is the modality of choice for non-invasive recognition of aortic and subaortic abnormalities. In this report we describe, in a 47-year-old white man with subvalvular aortic aneurysm associated to aortic bicuspid valve, the echocardiographic diagnosis and cardiac intervention of aortic valve replacement with surgical obliteration of the orifice. A good surgical result was confirmed by an echocardiographic transthoracic examination performed after 6 months.

[Two cases of postpartum pubis diastasis mistaken for neurological complications of epidural analgesia]. / Dos casos de diástasis de pubis postparto interpretados como complicación neurológica de la analgesia epidural.

Two healthy 31- and 34-year-old parturients received uncomplicated epidural analgesia for labor and delivery using standard techniques. Twenty-four and 12 hours postpartum, respectively, they developed severe lower back pain and difficulty moving their lower extremities. At first the symptoms were attributed to neurological complications of epidural analgesia and for this reason the anesthetist was called. Although both women appeared healthy and the neurological examinations were normal, emergency computed tomography scans were performed to rule out spinal compression because of the severity of pain and difficulty of movement. The diagnosis was only established after suspecting pubis diastasis, confirmed by palpation of symphysis gaps of 3 and 2 cm, respectively. Pelvic dysfunction associated with pregnancy and labour is a complication whose incidence varies from 1 in 300 to 1 in 30,000. It presents with severe pain located in the areas supplied by pudendal and genitofemoral nerves. The pain may radiate to the sacroiliac joints and shoot down the buttocks and legs. In the most severe cases it may be accompanied by urinary dysfunction and inability to walk. If the clinical features are not recognized, it can be difficult to differentiate pubis diastasis from severe neurological complications in women who have received a central nervous system block. We report two cases of peripartum pubis symphysis diastasis that were both initially mistaken for neurological complications of epidural analgesia for labor.

[Treatment of post-dural-puncture headache with intravenous cortisone]. / Tratamiento de la cefalea postpunción dural con hidrocortisona intravenosa.

Postdural puncture headache (PDPH) is the most frequent complication of procedures involving dural penetration for spinal anesthesia or following unintentional dural puncture during attempted epidural anesthesia or analgesia. PDPH causes serious problems for women who have just given birth, as they are unable to give adequate care to their infants. The causes of PDPH are poorly understood and treatments are therefore various and symptomatic; most are empirical and not all are effective. When conservative measures fail, an alternative that may be proposed is the blood patch, an invasive technique which is not without risk and which many patients reject. We report three cases of incapacitating PDPH in women after vaginal or caesarian delivery in which symptoms resolved with intravenous hydrocortisone treatment. Hydrocortisone treatment for PDPH has never been reported in the literature, but given our results, we consider that clinical trials are warranted to establish the efficacy of this treatment and to determine if there is a chance that it might offer an alternative to the blood patch.

Surgical management of a life-threatening retro-pharyngeal haematoma following trans-oesophageal echocardiography.

Trans-oesophageal echocardiography is generally considered a safe procedure, but occasional life-threatening complications have been reported. The aim of this clinical investigation is to outline the need of surgical management in cases of large retro-pharyngeal haematoma following trans-oesophageal echocardiography. In the case reported here, a patient with cervical spondylosis on anti-coagulant therapy was referred to the Head and Neck Department because of a retro-pharyngeal haematoma with severe upper airway obstruction following transoesophageal echocardiography. Tracheotomy was required to guarantee respiratory function, while trans-cervical surgery was performed to evacuate the haematoma. Total recovery was achieved within 10 days. In conclusion, the head and neck surgeon should consider the need of surgical management in cases of retro-pharyngeal haematoma following trans-oesophageal echocardiography.

Effects of long-term disease-modifying antirheumatic drugs on endothelial function in patients with early rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of the disease and the quality of life of these patients, but little is known about the effects of DMARDs on CV risk and endothelial dysfunction. Our goal was to examine the effects of long-term therapy with DMARDs on endothelial function and disease activity in early RA (ERA). Twenty-five ERA patients (mean age 52 ± 14.6 years, disease duration 6.24 ± 4.10 months) without evidence of CV involvement were evaluated for disease activity score (DAS-28), 2D-echo derived coronary flow reserve (CFR), common carotid intima-media thickness (IMT) and plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 18 months of treatment with DMARDs (10 patients with methotrexate and 10 with adalimumab). DMARDs significantly reduced DAS-28 (6.0 ± 0.8 vs. 2.0 ± 0.7; P < 0.0001) and improved CFR (2.4 ± 0.2 vs. 2.7 ± 0.5; P < 0.01). Common carotid IMT and plasma ADMA levels did not show significant changes. The present study shows that DMARDs, beyond the well known antiphlogistic effects, are able to improve coronary microcirculation without a direct effect on IMT and ADMA, clinical markers of atherosclerosis. Treatment strategies in ERA patients with high inflammatory activity must be monitored to identify beneficial effects on preclinical markers of vascular function.

Effects of treatment strategy on endothelial function.

A large body of evidence indicates that endothelial dysfunction is a characteristic of patients with arterial hypertension. As functional abnormalities lead to impaired endothelium-dependent vasodilation, this early step of atherogenesis is potentially reversible. In addition to reducing blood pressure, the major families of anti-hypertensive drugs have a number of pleiotropic effects that could improve endothelial function. In particular, the renin-angiotensin system plays an important role in the pathogenesis of both arterial hypertension and endothelial dysfunction, and so drugs capable of limiting the dangerous effects of this hormonal axis, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and renin inhibitors, could help prevent/delay/reverse the atherosclerotic process. New third-generation ß-blockers and 5-phosphodiesterase inhibitors may affect endothelial function. Furthermore, the HMGCoA-reductase inhibitors currently used to reduce cholesterol levels have major pleiotropic anti-inflammatory and anti-hypertensive effects. The preservation or recovery of endothelial function in hypertensive patients is crucial to inhibit the development of atherosclerosis and the onset of cardiovascular events. This review focuses on the ancillary effects of hypertensive drugs and HMGCoA-reductase inhibitors that go beyond lowering blood pressure and cholesterol levels.

From endothelial dysfunction to atherosclerosis.

It has recently emerged that endothelial dysfunction is an early step in the development of atherosclerosis and is mainly characterised by a reduction in the bioavailability of nitric oxide. All of the traditional cardiovascular (CV) risk factors (dyslipidemia, arterial hypertension, hyperglycemia and diabetes) are associated with endothelial dysfunction, and oxidised low-density lipoproteins, the renin-angiotensin axis and insulin resistance play important roles in the pathogenesis of impaired endothelial function. The increased expression of adhesion molecules and pro-inflammatory cytokines leads to abnormal endothelium-dependent vasodilation which could be investigated using vasoreactivity tests such as flow-mediated dilation in the brachial artery. Recently, new evidences showed that the immune system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis with a particular regard towards autoimmunity. The high prevalence of the atherosclerotic process in systemic autoimmune diseases supports the hypothesis of the immune pathogenesis. Evaluating coronary microvascular dysfunction by means of transthoracic echocardiography with non-invasive coronary flow reserve assessment is particularly interesting as it could detect preclinical impairment of coronary microvascular function. The discovery that the mechanisms responsible for endothelial damage have a genetic basis could improve the approach to CV diseases. This review summarises the most important aspects of the pathogenesis and development of endothelial dysfunction, with particular attention to the role of traditional CV risk factors, the usefulness of vasoreactivity tests, and the future perspectives opened by genetic studies.