Scoping review of chronic rhinosinusitis proteomics.

BACKGROUND: Progressive advances in proteomic technology has improved our understanding of the chronic rhinosinusitis (CRS) pathogenesis and endotypes. This scoping review aims to present a comprehensive and descriptive analysis of nasal mucosa and mucus proteome of CRS patients. METHODOLOGY: Studies investigating the proteome of nasal mucosa and mucus from healthy and CRS patients via mass spectrometry were included. Critical appraisal of methodological quality was conducted with extraction of protein lists. Gene set enrichment analysis (GSEA) was performed on studies including CRS patients. RESULTS: 2962 proteins were identified in the 21 studies included in this review. Eleven studies investigated the nasal mucus proteome and ten studies investigated the nasal mucosa proteome. Studies demonstrated heterogeneity in patients, sampling and mass spectrometry methodology. Samples from CRS patients suggested a trend in enrichment of immune system and programmed cell death pathways. Increased expression of proteins involved in cellular components including the cytoskeleton and adherens junctions was also present in CRS. CONCLUSIONS: Alterations in the healthy sinonasal proteome may lead to the increased immunological, metabolic and tissue remodeling processes observed in CRS. However, it is difficult to draw significant conclusions from the GSEA due to the heterogeneity present in the limited literature available. These findings allow us to direct further research to better understand CRS pathogenesis and its endotypes.

Precipitating anti-dsDNA peptide repertoires in lupus.

Anti-double-stranded (ds)DNA autoantibodies are prototypical serological markers of systemic lupus erythematosus (SLE), but little is known about their immunoglobulin variable (IgV) region composition at the level of the secreted (serum) proteome. Here, we use a novel proteomic workflow based on de novo mass spectrometric sequencing of anti-dsDNA precipitins to analyse IgV subfamily expression and mutational signatures of high-affinity, precipitating anti-dsDNA responses. Serum anti-dsDNA proteomes were oligoclonal with shared (public) expression of immunoglobulin (Ig)G heavy chain variable region (IGHV) and kappa chain variable region (IGKV) subfamilies. IgV peptide maps from eight subjects showed extensive public and random (private) amino acid replacement mutations with prominent arginine substitutions across heavy (H)- and light (L)-chains. Shared sets of L-chain complementarity determining region 3 (CDR3) peptides specified by arginine substitutions were sequenced from the dominantly expressed IGKV3-20 subfamily, with changes in expression levels of a clonal L-chain CDR3 peptide by quantitative multiple reaction monitoring (MRM) paralleling the rise and fall of anti-dsDNA levels by Farr radioimmunoassays (RIA). The heavily mutated IgV peptide signatures of precipitating anti-dsDNA autoantibody proteomes reflect the strong selective forces that shape humoral anti-dsDNA responses in germinal centres. Direct sequencing of agarose gel precipitins using microlitre volumes of stored sera streamlines the antibody sequencing workflow and is generalizable to other precipitating serum antibodies.

Subcutaneous administration of tocilizumab is effective in myointimal hyperplasia remodelling in refractory Takayasu arteritis.

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown origin that involves large and mediumsized arteries, primarily the aorta and its major branches. TA is a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always effective or safe. Interleukin 6 (IL-6) has emerged as a key cytokine in the pathogenesis of TA and its serum levels have been shown to well correlate with disease activity. We report a 19 years old female patient with TA refractory to conventional immunosuppressive agents, successfully treated with subcutaneous tocilizumab, a humanized monoclonal antibody against IL-6 receptor, in which ultrasonography (US) was used as imaging tool to follow up the patient. Currently, clinical indices of disease activity, inflammatory markers, carotid intima media thickness (cIMT) as well as carotid pulse wave velocity (cPWV) normalised, while the prednisone dosage has been tapered. Tocilizumab appears to be a good option in refractory TA, with a remarkable steroid-sparing effect. In addition, it seems to have a favourable effect on endothelial function, as it improved cIMT and PWV.

Extended boiling of peanut progressively reduces IgE allergenicity while retaining T cell reactivity.

BACKGROUND: Current peanut oral immunotherapy is hampered by frequent adverse events. It has been shown that boiling can reduce peanut allergenicity. Hypoallergenic peanut products have the potential to reduce treatment-related reactions during desensitization. OBJECTIVE: To show that extended boiling (for up to 12 h) can progressively reduce peanut allergenicity while retaining T cell reactivity. METHODS: Raw peanuts were boiled for half, 1, 2, 4 and 12 h in deionized water. After dehydration, boiled and raw peanuts were ground, defatted and soluble proteins extracted in PBS and cooking water (leachate) retained. SDS-PAGE, Western blot, inhibition ELISA, mass spectrometry and skin prick test were used to characterize changes to peanut allergens and human IgE reactivity. T cell responses to raw and boiled peanut extracts were determined by proliferation of CD4+/CD25+/CD134+ T cells in peanut-allergic and non-allergic individuals. RESULTS: Extended boiling progressively reduced peanut allergenicity through a combination of leaching of allergens into cooking water, fragmentation of allergens and denaturation of conformational epitopes. Two-hour boiling led to an eightfold reduction in IgE binding capacity of boiled peanuts as determined by inhibition ELISA, while 12-h boiling led to a 19-fold reduction. Mass spectrometry revealed an increasing number of unique allergen peptides with longer boiling times. Raw, 2- and 12-h boiled peanut extracts were equivalent in their ability to stimulate T cell activation and proliferation. CONCLUSION AND CLINICAL RELEVANCE: Progressive reduction in peanut allergenicity with extended boiling does not affect T cell reactivity. Boiled peanuts may be a candidate for oral immunotherapy.

Purification of α-synuclein containing inclusions from human post mortem brain tissue.

UNLABELLED: Comparison with existing methods. BACKGROUND: Neurodegenerative disorders affect a large proportion of the elderly population. A group of disorders, known as the α-synucleinopathies, are characterised by the presence of α-synuclein-containing protein inclusions, such as Lewy Bodies (LBs) found in neurons from Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB), and Glial Cytoplasmic Inclusions (GCIs) found in oligodendrocytes from Multiple System Atrophy (MSA). The analysis of the protein composition of inclusions has been hindered by limitations of methods for isolating the inclusions from the surrounding tissue. METHOD: Four modifications were made to the published method for GCI purification by Gai et al. (1999) which were: collecting the entire inclusion-containing part of the Percoll gradient; lysis of nuclei prior to DNAse digestion; limited tryptic digestion to release inclusions from the cytoskeletal meshwork; and increased antibody and magnetic bead concentrations/volumes to capture the larger amounts of inclusions. RESULTS: The optimised method gave a 28-fold increase in yield compared to the published method of Gai et al. (1999). A 2D-DIGE comparison revealed a 3.8-fold increase in α-synuclein enrichment and a corresponding 5.2-fold reduction in tubulin contamination. This method was also successfully adapted to the purification of LBs from DLB tissue. A 2D-DIGE comparison of purified GCIs (n=2) revealed that GCIs consist of 11.7% α-synuclein, 1.9% α-ß-crystallin and 2.3% 14-3-3 proteins compared to 8.5%, 2.0% and 1.5% in LBs, respectively. CONCLUSIONS: This study has generated an improved method for the purification of α-synuclein-containing inclusions with a yield sufficient for multiple forms of analysis.

Lupus anti-ribosomal P autoantibody proteomes express convergent biclonal signatures.

Lupus-specific anti-ribosomal P (anti-Rib-P) autoantibodies have been implicated in the pathogenesis of neurological complications in systemic lupus erythematosus (SLE). The aim of the present study was to determine variable (V)-region signatures of secreted autoantibody proteomes specific for the Rib-P heterocomplex and investigate the molecular basis of the reported cross-reactivity with Sm autoantigen. Anti-Rib-P immunoglobulins (IgGs) were purified from six anti-Rib-P-positive sera by elution from enzyme-linked immunosorbent assay (ELISA) plates coated with either native Rib-P proteins or an 11-amino acid peptide (11-C peptide) representing the conserved COOH-terminal P epitope. Rib-P- and 11-C peptide-specific IgGs were analysed for heavy (H) and light (L) chain clonality and V-region expression using an electrophoretic and de-novo and database-driven mass spectrometric sequencing workflow. Purified anti-Rib-P and anti-SmD IgGs were tested for cross-reactivity on ELISA and their proteome data sets analysed for shared clonotypes. Anti-Rib-P autoantibody proteomes were IgG1 kappa-restricted and comprised two public clonotypes defined by unique H/L chain pairings. The major clonotypic population was specific for the common COOH-terminal epitope, while the second shared the same pairing signature as a recently reported anti-SmD clonotype, accounting for two-way immunoassay cross-reactivity between these lupus autoantibodies. Sequence convergence of anti-Rib-P proteomes suggests common molecular pathways of autoantibody production and identifies stereotyped clonal populations that are thought to play a pathogenic role in neuropsychiatric lupus. Shared clonotypic structures for anti-Rib-P and anti-Sm responses suggest a common B cell clonal origin for subsets of these lupus-specific autoantibodies.

An immunodominant La/SSB autoantibody proteome derives from public clonotypes.

The La/SSB autoantigen is a major target of long-term humoral autoimmunity in primary Sjögren's Syndrome (SS) and systemic lupus erythematosus. A majority of patients with linked anti-Ro60/Ro52/La responses target an NH2-terminal epitope designated LaA that is expressed on Ro/La ribonucleoprotein complexes and the surface membrane of apoptotic cells. In this study, we used high-resolution Orbitrap mass spectrometry to determine the clonality, isotype and V-region sequences of LaA-specific autoantibodies in seven patients with primary SS. Anti-LaA immunoglobulin (Ig)Gs purified from polyclonal sera by epitope-specific affinity chromatography were analysed by combined database and de-novo mass spectrometric sequencing. Autoantibody responses comprised two heavily mutated IgG1 kappa-restricted monoclonal species that were shared (public) across unrelated patients; one clonotype was specified by an IGHV3-30 heavy chain paired with IGKV3-15 light chain and the second by an IGHV3-43/IGKV3-20 pairing. Shared amino acid replacement mutations were also seen within heavy and light chain complementarity-determining regions, consistent with a common breach of B cell tolerance followed by antigen-driven clonal selection. The discovery of public clonotypic autoantibodies directed against an immunodominant epitope on La, taken together with recent findings for the linked Ro52 and Ro60 autoantigens, supports a model of systemic autoimmunity in which humoral responses against protein-RNA complexes are mediated by public sets of autoreactive B cell clonotypes.

Henoch-Schönlein purpura in a patient with bowel bypass syndrome.

Henoch-Schönlein purpura (HSP) is a common vasculitis being characterized by the classic tetrad of nonthrombocytopenic palpable purpura, arthritis or arthralgias, gastrointestinal and renal involvement. Antigen-antibody (IgA) complexes activate the alternative complement pathway, resulting in inflammation and small vessels vasculitis. We present the case of a 53 years old Italian woman with HSP who was previously hospitalized for purpura skin lesions of the lower legs and diarrhea; a skin biopsy showed a leukocytoclastic vasculitis with perivascular accumulation of neutrophils and mononuclear cells. She was treated with immunosuppressive therapy. After 8 months she was hospitalized again for a recurrent episode of purpura skin lesions of the lower legs. At age 49 she was affected by obesity (BMI = 41.6 Kg/m2), treated via a bilio-pancreatic diversion that led, within a year, to a BMI reduction (25 Kg/m2). We suppose that bariatric surgery played a role on the development of autoimmune phenomena and that the formation of immunecomplexes is secondary to the excess of intestinal bacterial antigens. A cyclic therapy with Paromomicine 500 mg twice daily and Metronidazole 250 mg twice daily was performed with a clear up of the clinical picture. In medical literature are described numerous complications which include arthritis, erythema nodosum-like lesions, eruptions and other skin manifestations in patients who have undergone jejunocolic bypass. This case report describes for the first time the presence of HSP in a patient with bowel bypass syndrome and it is also able to demonstrate the relationship between the intestinal bacterial overgrowth and the systemic autoimmune system.

Intracranial extension of salivary gland tumors.

OBJECTIVE: The aim of this report is to describe 3 cases of salivary gland tumors with intracranial extension associated to an extracerebral mass lesion, and to discuss the frequence, pathology and treatment of these very rare localizations. CLINICAL MATERIAL: The 3 patients were 1 woman and 2 men, aged 44, 53 and 74 years, respectively. The primary tumors were an adenocarcinoma and a malignant oncocytoma of the parotid gland and an adenoid cystic carcinoma of the submandibular gland. The location of the intradural extra-axial tumor was the middle fossa and temporal region in 2 cases and the cerebellopontine angle in 1. Surgical treatment consisted in the seemingly complete removal of 2 tumors with middle fossa localization and partial removal of the cerebellopontine angle lesion. Radiotherapy was administered in all 3 cases and chemotherapy in 2. RESULTS: 1 patient is alive and free of recurrence 32 months after removal of the intracranial tumor; 2 other patients died 28 months and 12 months postoperatively. CONCLUSIONS: The intracranial extension of salivary gland tumors is a very rare event. An aggressive surgical resection followed by radiotherapy is justified in cases with significant intracranial mass lesions and scarce bone and dural involvement.

Local versus diffuse recurrences of meningiomas: factors correlated to the extent of the recurrence.

OBJECTIVE: The aim of this study is to evaluate the factors correlated with the different patterns (local, peripheral and diffuse) of meningioma recurrence. MATERIAL AND METHODS: 55 patients with benign (WHO I) meningiomas which recurred after seemingly complete removal were reviewed; 40 (Group I) had local or peripheral recurrences (< 3 cm from the initial dural attachment) and 15 (Group II) had distant and diffuse recurrences. Patient age and sex, tumor location, interval of recurrence, tumor shape, type of brain-tumor interface, histological subtype, mitotic index (MI) and progesterone receptor (PR) expression of the initial tumor, histological WHO Grade of the recurrent tumor and patient outcome were analyzed and correlated with the pattern of recurrence. RESULTS: Flat-shaped meningiomas with large dural attachment showed a significantly higher rate of diffuse recurrences than round tumors, whereas the brain-tumor interface and the tumor location were not relevant (excepting the lack of convexity meningiomas in the group of diffuse tumors). There were no significant differences of histology, MI and PR expression of the initial tumor and histological grade of the recurrent tumor between the two groups. CONCLUSIONS: The different patterns of meningioma recurrences (local, peripheral, diffuse) are not correlated with the tumor location and histology and do not represent a different biological tumor progression. We agree that most unexpected extensive recurrences result from a more extensive microscopic dural involvement.

Post automatic implantable cardioverter defibrillator implant therapies: drugs and ablative techniques.

The aim of this article is to report the evidences about the use of drugs and ablation after implantation of a cardioverter defibrillator. Drugs can be utilized to prevent appropriate and inappropriate shocks, can influence positively or negatively defibrillation threshold, can be useful for the treatment of electrical storm. Ablation can be performed for direct cure of coexisting atrial and ventricular tachyarrhythmias or for AV node modulation. In particular, previous data demonstrate that rescue ventricular tachycardia ablation of drug-refractory electrical storm is possible by a substrate-orientated ablation approach even in patients with complex chronic infarction and various ventricular tachycardias. At the end of this article it is described how remote monitoring, a new very promising technical improvement, can be utilized for deciding, almost in real time, the use of both these therapies or for controlling their efficacy.

Is implantable defibrillator indicated in all patients on cardiac resynchronization therapy?

Implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) have been introduced during the recent years to improve survival, decrease hospital readmissions and mortality, and to improve functional status and quality of life for patients with heart failure and left ventricular systolic dysfunction (LVSD). Studies which evaluated the use of CRT or ICD alone or compared CRT with CRT-ICD in patients with heart failure and LVSD are listed in this article. The results obtained are already influencing clinical practice in the US, where it has been estimated that 90% of patients receiving a CRT device now are being implanted with an ICD component. However, it is still today debated whether patients with LVSD and heart failure should be routinely offered a CRT-ICD. In fact, there are some issues that still should be solved before to establish indication for CRT-D in all heart failure patients with an indication for CRT: 1) a non complete agreement among the different societies which wrote recommendations for guidelines (a comparative table is reported); 2) a better identification of implantable patients and an amelioration of utilized devices; 3) economic and ethical ramifications of this therapy. Anyway still now the crucial question is: ''Can resynchronization be done in isolation or must be accompanied by an ICD device?''. To answer to this question we can only express which is, in our opinion, the actual position of many physicians who work in the field of pacing and electrophysiology: ''The lesson to be learned is that we still can not predict surely which patient will die of sudden death. Until a method of identifying the high risk patients can be developed, the safest strategy should be to advise a combined ICD-CRT device for patients with indication for CRT''.

Role of natriuretic peptides in heart failure patients with special reference to those on cardiac resynchronization therapy.

In recent years natriuretic peptides (NPs) have emerged as important tools for evaluation of heart failure patients. Since its approval by the Food and Drug Administration (FDA) in November 2000, recent surveys suggest that approximately 83% of hospitals in the US use some type of NP testing. Although NP testing was originally focused on rapid diagnosis of patients presenting to the emergency department with shortness of breath, clinicians regularly look to NPs for diagnosing minimally symptomatic or asymptomatic left ventricular dysfunction, and using NPs levels in clinic to help ascertain when decompensation is present. NP testing is now included in the guidelines for the diagnosis and treatment of chronic heart failure and in the Italian Consensus Document for the clinical use of NPs. Recommendations indicate that assessment of NPs can be considered a reliable rule-out test of heart failure in primary care and in the emergency room even if they stated that the role for treatment monitoring or for prognostic evaluation needs to be determined. In recent years, cardiac resynchronization therapy (CRT) was introduced as a new treatment modality for patients with systolic heart failure and several studies suggest that plasma concentration of NPs ensues as a very useful parameter for evaluating and monitoring patients who undergo CRT. Thus this article aims not only to summarise data concerning NPs measurement in patients with heart failure, but also to indicate how these markers could be utilized in the future to objectively assess effects of CRT (identification of responders). In conclusion, if further studies will confirm above mentioned remarks, it would be possible that NPs evaluation can help to tailor the more suitable therapy for each heart failure patient and, therefore, to reduce the number of failures.

Aggressive eosinophilic granuloma of the parietal bone. An immunohystochemical study of Ki-67 expression.

Solitary eosinophilic granuloma (EG) of the skull is a rare lesion, the natural history of which is still to be defined. We report a case of a 26-year-old female who presented with progressive headache and nausea accompanied by a painful firm mass in her left parietal region, which grew very rapidly during the last two weeks before admission. Computed tomography scan showed an osteolytic lesion, which on magnetic resonance imaging appeared hyperintense on both T1- and T2-weighted images, with marked and heterogeneous enhancement after gadolinium administration. Total surgical excision of the lesion was performed and histopathological diagnosis was compatible with eosinophilic granuloma. Immuno-histochemical study of Ki-67 antigen expression was also performed with a labelling index of 10%. In a review of the pertinent literature, we found one case report showing a Ki-67 labelling index of 6.2% in a patient harboring EG of the occipital bone. These two relatively high percentages of proliferative activity suggest a role of local Langerhans'cell proliferation, along with that of inflammatory response, in the aggressive clinical course and rapid expansion observed in some rare cases of solitary eosinophilic granuloma.

Resynchronization of mitral valve annular segments reduces functional mitral regurgitation in cardiac resynchronization therapy.

AIM: Cardiac resynchronization therapy (CRT) reduces the severity of functional mitral regurgitation (FMR) in patients with heart failure and left bundle branch block. Our hypothesis was that the induction of a more synchronous mitral valve anulus contraction can be a mechanism of FMR reduction in CRT patients. METHODS: An echo tissue Doppler imaging (TDI) examination was performed at baseline and 6 months after biventricular pacing system implant in 30 patients (4 females and 26 males, 74.1+/-6.1 years) with dilatative or ischemic chronic heart failure, NYHA class = or >III, ejection fraction (EF) = or <35% and QRS = or >140 ms. EF, Myocardial Performance Index (MPI), left end-diastolic and systolic volumes (LVEDV, LVESV), mitral regurgitation jet area/left atrial area (JA/LAA), effective regurgitant orifice area (EROA), mitral anulus contraction (MAC) were evaluated. Using TDI, at the 6 left ventricle (LV) basal segments the time to the peak myocardial sustained systolic velocity (Ts) and the standard deviation (SD) of TS were evaluated. RESULTS: At 6 months follow-up NYHA class, EF, MPI were significantly improved, LV volumes were reduced. FMR degree, evaluated both as JA/LAA and EROA, was significantly reduced. This effect was associated with the 6 basal segments resynchronization and with a more effective annular contraction. CONCLUSIONS: Our data show that CRT by resynchronizing left ventricular basal segments produces a more effective mitral valve annulus contraction and contributes to FMR improvement. Further studies need to evaluate if this could be taken into account as new therapeutic perspective of functional mitral valve regurgitation.

Randomized crossover comparison of right atrial appendage pacing versus interatrial septum pacing for prevention of paroxysmal atrial fibrillation in patients with sinus bradycardia.

BACKGROUND: New atrial pacing techniques and overdrive pacing algorithms have been introduced to prevent atrial fibrillation. This study was designed to test the hypotheses that (1) interatrial septum pacing (IASP) at the triangle of Koch would be more effective than right atrial appendage pacing (RAAP) in preventing paroxysmal atrial fibrillation (PAF) in patients with sinus bradycardia and (2) an algorithm (CAP) designed to achieve constant atrial capture would increase the efficacy of rate-responsive atrial pacing. METHODS: We studied 46 patients with PAF and sinus bradycardia implanted with a DDD(R) (Medtronic Thera) pacemaker. Twenty-four patients (6.0 +/- 10.1 PAF episodes/month within 3 months before study) were randomized to RAAP and 22 patients (5.4 +/- 7.1, not significant) to IASP. Within each arm 2 randomized crossover periods of CAP-OFF and CAP-ON function were programed. RESULTS: The PAF episodes per month significantly decreased in the RAAP (CAP-OFF: 2.1 +/- 4.2, P <.05; CAP-ON: 1.9 +/- 3.8, P <.05) and in the IASP group (CAP-OFF: 0.2 +/- 0.5, P <.05; CAP-ON: 0.2 +/- 0.5, P <.05). Values were significantly lower in the IASP group than in the RAAP group in both CAP-OFF (0.2 +/- 0.5 vs 2.1 +/- 4.2, P <.05) and CAP-ON (0.2 +/- 0.5 vs 1.9 +/- 3.8, P <.05) conditions. PAF burden was significantly lower in the IASP than in the RAAP group in CAP-OFF (47 +/- 84 min/d vs 140 +/- 217, P <.05) and in CAP-ON (41 +/- 72 vs 193 +/- 266, P <.05) conditions. No differences were observed within each arm in PAF burden between the 2 crossover CAP programing periods. CONCLUSIONS: Rate-adaptive IASP at the triangle of Koch is more effective than RAAP in preventing PAF in patients with sinus bradycardia. In our sample of patients no additional clinical benefit is furnished by the CAP algorithm.

Increased cardiac sympathetic activity and insulin-like growth factor-I formation are associated with physiological hypertrophy in athletes.

Physiological hypertrophy represents the adaptive changes of the heart required for supporting the increased hemodynamic load in regularly trained healthy subjects. Mechanisms responsible for the athlete's hypertrophy still remain unknown. In 15 trained competitive soccer players and in 15 healthy men not engaged in sporting activities (sedentary control subjects) of equivalent age, we investigated the relationship among cardiac growth factor formation, cardiac sympathetic activity, and left ventricular morphology and function. Cardiac formation of insulin-like growth factor (IGF)-I, endothelin (ET)-1, big ET-1, and angiotensin (Ang) II was investigated at rest by measuring artery-coronary sinus concentration gradients. Cardiac sympathetic activity was studied by [(3)H]norepinephrine (NE) kinetics. Cardiac IGF-I, but not ET-1, big ET-1, and Ang II, formation was higher in athletes than in control subjects (P<0.01). NE levels in arterial and peripheral venous blood did not differ between groups. In contrast, coronary sinus NE concentration was higher in athletes than in control subjects (P<0.01). Cardiac, but not total systemic, NE spillover was also increased in athletes (P<0.01), whereas cardiac [(3)H]NE reuptake and clearance were not different. Echocardiographic modifications indicated a volume overload-induced hypertrophy associated with increased myocardial contractility. Multivariate stepwise analysis selected left ventricular mass index as the most predictive independent variable for cardiac IGF-I formation and velocity of circumferential fiber shortening for cardiac NE spillover. In conclusion, increased cardiac IGF-I formation and enhanced sympathetic activity selectively confined to the heart appear to be responsible for the physiological hypertrophy in athletes performing predominantly isotonic exercise.

Altered values of heart rate variability in patients with relapse of atrial fibrillation during the first week after electrical cardioversion: preliminary data.

BACKGROUND: It has not so far been elucidated whether the autonomic nervous system plays a role in the pathogenesis of atrial fibrillation relapse after electrical cardioversion. METHODS: In 40 consecutive patients with atrial fibrillation (22 males, 18 females, mean age 60 +/- 2 years) submitted to successful electrical cardioversion (external in 26 and low-energy internal in 14) we evaluated the heart rate variability (24-hour Holter recording) immediately after restoration of sinus rhythm in order to assess the cardiac sympatho-vagal drive. RESULTS: Patients with atrial fibrillation relapse within the first week of electrical cardioversion were characterized by a significantly higher low/high frequency ratio. CONCLUSIONS: Despite the heterogeneity of the studied population (concerning both the therapy and etiology of atrial fibrillation), our data strongly suggest that the evaluation of the low/high frequency ratio by means of power spectral analysis immediately after electrical cardioversion is a useful tool for the identification of those patients who are prone to atrial fibrillation recurrence. Our conclusions are supported by the finding of high positive and negative predictive values for the low/high frequency ratio both in the 24-hour period and during daytime.

Mapping the organization of atrial fibrillation with basket catheters. Part II: Regional patterns in chronic patients.

The aim of this study was to investigate the spatial patterns of organization of fibrillation in the right atrium using bipolar recordings from a basket catheter in a population of 17 patients with persistent AF. The number of occurrences (NO) (i.e., the number of points laying on the baseline) was used as an objective measure of organization. This parameter significantly matches Wells' criteria for the classification of bipolar recordings during AF. The anatomic correspondence of the splines with eight atrial regions (namely anterior free wall, lateral free wall, posterolateral free wall, posterior free wall, posterior atrial septum, atrial septum, tricuspid valve, and anterior tricuspid valve) was assessed by fluoroscopic projections and electrogram morphology. Each region was further divided into high, mid-high, mid-low, and low segments. It was observed that individual and well-defined patterns of organization characterize the electrical activity of the right atrium in patients with persistent AF. When observed over 10 minutes, these patterns are rather stable in time. In each patient, the NO measurements were significantly different in the various right atrium regions (P < 0.0001 for all patients, Friedman test). The NO averaged over the population was significantly different among the regions (P < 0.001, Kruskal-Wallis test), owing to a common disorganized pattern observed in the tricuspid valve and anterior tricuspid valve regions. When these regions were removed from the analysis, the differences among the remaining regions were not statistically significant (P = 0.77). In conclusion, the quantitative assessment of organization in the entire right atrium showed an individual rather than common distribution. This may have implications in the choice of regions candidate for ablation.

Clinical evaluation of disorganization during atrial fibrillation as a guide to radiofrequency ablation.

Aim of this study was to investigate the spatial patterns of organization of fibrillation in the right atrium using bipolar recordings from a basket catheter. Study population consists of 17 patients with persistent atrial fibrillation (AF), selected a priori for low energy internal cardioversion. Organization was measured by the number of occurrences--i.e. the percentage number of points laying on the baseline--which has been demonstrated to match Wells' criteria for the classification of AF. Well-defined and stable patterns of organization characterize the electrical activity of the right atrium in these patients. The organization in the entire right atrium showed an individual rather than common distribution. This may have implications in the choice of regions candidate for ablation.