Coronary artery calcifications predict long term cardiovascular events in non diabetic Caucasian hemodialysis patients.

Vascular calcifications are frequent in chronic renal disease and are associated to significant cardiovascular morbidity and mortality. The long term predictive value of coronary artery calcifications detected by multi­layer spiral computed tomography for major cardiovascular events was evaluated in non­diabetic Caucasian patients on maintenance hemodialysis free of clinical cardiovascular disease. Two­hundred and five patients on maintenance hemodialysis were enrolled into this observational, prospective cohort study. Patients underwent a single cardiac multi­layer spiral computed tomography. Calcium load was quantified and patients grouped according to the Agatston score: group 1 (Agatston score: 0), group 2 (Agatston score 1­400), group 3 (Agatston score 401­1000) and group 4 (Agatston score >1000). Follow­up was longer than seven years. Primary endpoint was death from a major cardiovascular event. Actuarial survival was calculated separately in the four groups with Kaplan­Meier method. Patients who died from causes other than cardiovascular disease and transplanted patients were censored. The "log rank" test was employed to compare survival curves. One­hundred two patients (49.7%) died for a major cardiovascular event during the follow­up period. Seven­year actuarial survival was more than 90% for groups 1 and 2, but failed to about 50% for group 3 and to <10% for group 4. Hence, Agatston score >400 predicts a significantly higher cardiovascular mortality compared with Agatston score <400 (p<0.0001); furthermore, serum Parathyroid hormone levels > 300 pg/l were associated to a lower survival (p < 0.05). Extended coronary artery calcifications detected by cardiac multi­layer spiral computed tomography, strongly predicted long term cardiovascular mortality in nondiabetic Caucasian patients on maintenance hemodialysis. Moreover, it was not related to conventional indices of atherosclerosis, but to other non­traditional risk factors, as serum Parathyroid hormone levels. A full cost­benefit analysis is however necessary to justify a widespread use of cardiac multi­layer spiral computed tomography in clinical practice.

Biocompatibility assessment of haemodialysis membrane materials by proteomic investigations.

The exposure of blood to an artificial surface such as the haemodialysis membrane results in the nearly instantaneous deposition of a layer of plasma proteins. The composition of the protein layer profoundly influences all subsequent events, and to a large extent determines the biocompatibility of the biomaterial. In the present study, we examine the protein adsorption capacity and coagulation profiles of the polysulfone-based helixone material in comparison to cellulose triacetate. A differential profiling investigation using shotgun proteomics data-independent analysis was applied to eluates obtained with each membrane after a dialysis session, in order to assess the function of desorbed proteins. Functional classification and network analysis performed using bioinformatics tools shed light on the involvement of adsorbed proteins into important molecular processes, such as lipid transport and metabolism, cell growth differentiation and communication, and the coagulation cascade. The collected evidence was further validated by targeted mass spectrometry using selected reaction monitoring on proteotypic transitions of key protein effectors, confirming the different panels of adsorbed protein on each membrane. The coagulation profile during haemodialysis of patients under polysulfone-based helixone filter cartridges was also assessed showing a slightly higher platelet activation profile after the dialysis session. The overall collected evidence highlights a modulation of the coagulation biological pathway during haemodialysis, which is largely influenced by the biomaterial used.

Device monitoring of heart failure in cardiac resynchronization therapy device recipients: a single-center experience with a novel multivector impedance monitoring system.

OBJECTIVES: We investigated the performance of a new intrathoracic multivector impedance monitoring system for the prediction of heart failure events in consecutive device-implanted patients. METHODS: Eighty heart failure patients implanted with biventricular defibrillators with multivector impedance monitoring capability were prospectively enrolled. Clinical heart failure status and impedance data were assessed during follow-up and if patients presented with an alert or heart failure deterioration. RESULTS: During follow-up (8.0 ± 4.4 months), 56 events of device alert for fluid index increase were identified in 29 patients, and a total of 39 heart failure events (defined by worsening of heart failure signs and symptoms) occurred in 23 patients. The sensitivity and positive predictive value (PPV) for heart failure deterioration was 61.5 and 42.9%, respectively. False-positive alerts occurred in 23 of 80 patients (28.8%), for an episode rate of 0.60 a year. Among all clinical heart failure events, decompensation caused hospitalization in 13 cases (33.3%), seven of them were preceded by an alert condition (53.8%) resulting in a sensitivity of 53.8% and a PPV of 17.9%. CONCLUSION: The present study confirms the feasibility and clinical usefulness of this novel multivector impedance monitoring system. It would be worthwhile to perform larger studies to assess its actual clinical value in heart failure patients.

Endothelial dysfunction is a marker of systemic response to the cardiac resynchronization therapy in heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) induces a significant improvement in patients with heart failure (HF), who are often characterized by the presence of endothelial dysfunction (ED) with impaired flow-mediated vasodilation (FMD). We aimed to study the ED in patients with HF candidates to CRT with defibrillator (CRT-D). METHODS AND RESULTS: We studied 57 consecutive patients affected by HF and undergoing CRT-D. At the baseline we recorded a high prevalence of ED (64.9%) with impaired FMD (4.1 ± 3.8%). After 12 months of CRT, we reported a marked increase of the mean FMD (8.8 ± 4.8% vs 4.1 ± 3.8%; P < .05) along with significant improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) functional class, and 6-minute walk test (6MWT); 42 patients (73.7%) were classified as responders according to standard criteria. FMD was related to LVEF (r = 0.169; P < .05), LVESV (r = -0.169; P < .05), NYHA functional class (r = -0.27; P < .051), and 6MWT (r = 0.360; P < .01). CONCLUSIONS: ED is not an independent predictor of CRT response, but it is able to intercept the systemic effects of CRT and is an affordable marker of response to CRT, especially in patients unable to perform the 6MWT.

A novel methodology for AV and VV delay optimization in CRT: results from a randomized pilot clinical trial.

The aim of this work was to determine whether the use of a newly developed methodology (Alg1) for AV and VV optimization improves cardiac resynchronization therapy (CRT) clinical and echocardiographic (ECHO) outcomes. In this single-center pilot clinical trial, 80 consecutive patients (79 % male; 70.1 ± 11.2 years) receiving CRT were randomly assigned to AV and VV optimization using Alg1 (group A) or standard commercial procedures (group B). Clinical status and ECHOs were analyzed at baseline (_0) , 3 (fu1), and 6 months (fu2) of follow-up evaluating left ventricular end systolic (LVESV) and end diastolic (LVEDV) volumes, ejection fraction (EF), Minnesota test, and 6-min walk test (6MWT). Alg1 is based on a cardiovascular model fed with patient data. Baseline characteristics did not differ significantly between groups. Group A had a better clinical outcome and reverse remodeling. Remodeling was calculated as the difference (Δ) between fu1 and _0 and between fu2 and fu1, respectively: [LVESV (ml): ΔA_fu1 = -55.3, ΔB_fu1 = -13.5, p_fu1 = 0.002; ΔA_fu2 = -22.8, ΔB_fu2 = 3.0, p_fu2 = 0.04], [LVEDV (ml): ΔA_fu1 = -61.9, ΔB_fu1 = -16.1, p_fu1 = 0.01; ΔA_fu2 = -30.4, ΔB_fu2 = 11.3, p_fu2 = 0.02]; Minnesota test: total (p_fu1 = 0.01; p_fu2 = 0.04), physical (p_fu1 = 0.01; p_fu2 = 0.03) and emotional scores (p_fu1 = 0.04; p_fu2 = 0.03) and in 6MWT (m) (p_fu2 = 0.008). No statistically significant difference was observed in QRS width. Compared with current standard of care, CRT optimization using Alg1 is associated with better outcomes, showing the power of a tailored CRT.

An increased endothelial-independent vasodilation is the hallmark of the neurally mediated syncope.

BACKGROUND: The neurally mediated syncope (NMS) is sustained by complex cardiac and vascular reflexes, acting on and amplified by central autonomic loops, resulting in bradycardia and hypotension. HYPOTHESIS: Our aim was to assess whether the pathophysiology of NMS is also related to an abnormal peripheral vasoreactivity. METHODS: We evaluated by ultrasound the flow-mediated vasodilation (FMD) and the nitrate-mediated dilation (NMD) in 17 patients with NMS, induced by drug-free tilt test in 6 subjects and by nitrate-potentiated tilt test in the other 11 cases; the syncope was classified as vasodepressive (VD) in 8 cases, cardioinhibitory (CI) in 7, and mixed in 2. RESULTS: The FMD was not different from controls (10.2 ± 4.5 vs 11.4 ± 3.9, P = ns), with normal recovery times; the NMD was greater in fainting subjects than in controls (26.7 ± 7.3 vs 19.0 ± 3.6, P < 0.05), with higher values in VD than in CI syncope (31.1 ± 7.0 vs 23.1 ± 5.0, P = ns); compared to controls, subjects with NMS showed normal recovery times after FMD but longer recovery times after nitrate administration (13.0 ± 5.6 vs 6.3 ± 0.7 minutes, P < 0.05). CONCLUSIONS: The evaluation of endothelial function supports evidence that NMS is characterized by a marked and sustained endothelial-independent vasodilation, in the presence of a normal FMD; vascular hyperreactivity in response to nitrate administration is particularly overt in vasodepressive syncope and can explain the high rate of responses to nitrate administration during tilt test.

Peripheral neurological disturbances, autonomic dysfunction, and antineuronal antibodies in adult celiac disease before and after a gluten-free diet.

Thirty-two consecutive adult celiac disease (CD) patients (pts), complaining of peripheral neuropathy (12 pts), autonomic dysfunction (17 pts), or both (3 pts), were evaluated to assess the presence of neurological damage (by clinical neurological evaluation and electrophysiological study) and antineuronal antibodies and to assess the effect of a gluten-free diet (GFD) on the course of the neurological symptoms and on antineuronal antibodies. At entry, 12 of 32 (38%) pts showed signs and symptoms of neurological damage: 7 of 12 (58%), peripheral neurological damage; 3 of 12 (25%), autonomic dysfunction; and 2 (17%), both peripheral neurological damage and autonomic dysfunction. The overall TNS score was 105 at entry. Anti-GM1 antibodies were present in 5 of 12 (42%) pts: 3 showed peripheral neurological damage and 2 showed both peripheral neurological damage and autonomic dysfunction. One year after the GFD was started, histological lesions were still present in only 10 of 12 (83%) pts. TNS score was 99, 98, 98, and 101 at the 3rd, 6th, 9th, and 12th month after the GFD was started, so it did not improve throughout the follow-up. None of the pts showed disappearance of antineuronal antibodies throughout the follow-up. We conclude that adult CD patients may show neurological damage and presence of antineuronal antibodies. Unfortunately, these findings do not disappear with a GFD.

Assessment of autonomic function in untreated adult coeliac disease.

AIM: Some recent studies showed that alteration of upper-gut motility in coeliac disease may be related to dysfunction of autonomic nervous system. The aim of our study was to investigate whether autonomic nervous system was altered in untreated and unselected coeliac disease patients. METHODS: We studied 8 untreated and consecutive coeliac disease patients (2 males and 6 females, age range 37+/-14.5 years). Histological evaluation of duodenal mucosa, anti-gliadin antibodies (AGA), antiendomysial antibodies (EMA) and anti-tTG antibodies and sorbitol H2 breath test were performed in all patients. Extrinsic autonomic neuropathy was assessed by the standardized measurement of cardiovascular reflexes (lying-to-standing, Valsalva manoeuvre, deep breathing, sustained handgrip). The results obtained were compared with a healthy, asymptomatic control group (6 males and 7 females, age range 42.3+/-13.5 years). RESULTS: Coeliac patients exhibited a lower increase of PAS as a response to isometric effort, a reduction of spectral power LF as a response to clinostatic position, but without statistical significance. Also they showed a lower tolerance to orthostatic position, associated with a latent disequilibrium of sympathetic-vagal balance, a relative prevalence of parasympathetic component of the autonomic function. However, these results were not statistically significant when compared with control group (P = n.s.). And they were unchanged after 6 and 12 mo of gluten-free diet. CONCLUSION: This study failed to confirm a significant correlation between autonomic dysfunction and coeliac disease, yet we could not exclude a role of autonomic dysfunction in the genesis of systemic symptoms in some coeliacs.

Non-invasive diagnostic and functional evaluation of cardiac and pulmonary involvement in systemic sclerosis.

BACKGROUND: The aim of the present study was to evaluate the role of non-invasive methods in the early detection of pulmonary and cardiac involvement in Systemic sclerosis (SSc) and to identify clinical and/or instrumental patterns of prognostic value. PATIENTS AND METHODS: Twenty female patients affected by SSc (8 with diffuse cutaneous SSc and 12 with limited cutaneous SSc) were enrolled in our study. Cardiac and pulmonary involvement (respiratory function tests and carbon monoxide lung diffusion [DLCO], chest radiography, high resolution computed tomography [HRCT] and lung perfusion magnetic resonance) were evaluated. RESULTS: All 18 patients studied with respiratory function tests showed a significant reduction of DLCO. HRCT was considerably more sensitive than traditional chest radiography (59% versus 28%; p<0.05). Lung perfusion MRI revealed normal findings in 15 patients. Abnormal lung perfusion MRI results were found only in 3 patients. Angina pectoris with electrocardiographic and scintigraphic ischemic changes, severe regional wall motion abnormalities and complex arrhythmias seemed to be associated with poor prognosis. CONCLUSION: Taken together these results indicate that a pulmonary involvement occurs both in limited and in diffuse cutaneous SSc patients and develops, in 83% of the cases, without any regional lung perfusion abnormality. Furthermore, cardiac involvement is detected in 65% of the cases as a consequence of a range of noxious events including myocardial ischemia, fibrosis and pressure overload which may result in ventricular dysfunction and arrhythmias. Lung perfusion MRI should be considered as a complementary diagnostic method for the functional evaluation of these symptoms in systemic sclerosis.