Long-term effect of atrial fibrillation on the evolution of mitral and tricuspid valve regurgitation.

Objective: The present study aims to identify the long-term effects of atrial fibrillation (AF) on atrial remodelling and on the progression of mitral/tricuspid valve regurgitation (MR/TR).Methods: The severity of MR/TR was assessed by the colour jet area and by multi-integrative approach at baseline and after a period of 65 ± 10 months in 37 patients with permanent AF, in 80 patients with non-permanent AF (of whom 43 were treated with ablation) and in 53 control patients with sinus rhythm.Results: At baseline, AF patients had larger MR jet areas than control patients. At follow up, progression of MR, expressed as delta MR jet area, was 0.05 ± 1.3 cm2 in the control group, 0.73 ± 2.1 cm2 in the non-permanent AF group and 1.95 ± 3.6 cm2 in the permanent AF group (p = .001). Severe MR at follow up was observed in 0%, 2.5%, 8%, respectively. There was a significant positive correlation between progression of MR and increase of left atrium volume (r = 0.31, p < .001). After adjustment for baseline clinical and echocardiographic parameters, permanent AF remained independently associated with the progression of MR. Although rhythm control was better with AF ablation than with medical treatment only, the MR evolution was similar. Comparable findings, albeit less pronounced, were observed for the association between of AF and TR progression.Conclusions: The presence of longstanding AF is associated with a significant progression of MR/TR mainly due to atrial remodelling. Our data showed a beneficial effect of sustained rhythm control, either medically or by ablation, on MR/TR progression.

VT Recurrence After Ablation: Incomplete Ablation or Disease Progression? A Multicentric European Study.

AIM: To determine whether ventricular tachycardia (VT) recurrences in arrhythmogenic RV cardiomyopathy (ARVC) and nonischemic cardiomyopathy (NICM) are related to incomplete ablation or disease progression. METHODS: ARVC and NICM patients with two substrate maps of the same diseased ventricle with an interprocedural delay of ≥12 months were included. Disease progression was defined as ≥1 factor: scar area progression (PROG, +5%), ventricular remodeling (dilatation [+25 mL] or decreased ejection fraction [-5%EF]). Incomplete ablation was defined as index VT recurrence or ablation in previously unablated regions inside index scar without PROG. RESULTS: Twenty patients from nine centers were included (80% male 55 ± 16 years, 7 ARVC and 13 NICM, LVEF 43 ± 14%). Mean delay was 28 ± 18 months. Disease progression occurred in 75% with ventricular remodeling in 70%: ventricular dilation in 45% (ARVC [71%]; NICM [38%]), decreased EF in 60% [RVEF in ARVC (71%); LVEF in NICM (54%)], and scar progression in 50% (in ARVC [57%] and NICM [46%]). Index VT recurrence was observed in 40%. Redo ablation sites were located in previously unablated regions inside the index scar in 70% of patients. VT recurrence following the second procedure was seen in 25%. Fifteen percent died during a follow-up of 17 ± 17 months. CONCLUSION: Disease progression is the rule in ARVC and NICM while scar progression occurs in half. However, even if disease progression is frequently observed, incomplete index ablation is the most common finding, strongly suggesting the need for more extensive ablation.

New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle.

Conotruncal defects (CTDs) represent 15-20% of all congenital heart defects. Mutations in a number of genes have been associated with CTD in humans and animal models. We investigated the occurrence and the prevalence of GATA4, NKX2.5, ZFPM2/FOG2, GDF1, and ISLET1 gene mutations in a large cohort of individuals with CTD, including tetralogy of Fallot with or without pulmonary atresia (TOF, 178 patients), double outlet right ventricle (DORV, 13 patients), and truncus arteriosus (11 patients). Denaturing high-performance liquid chromatography (DHPLC) analysis followed by bidirectional sequencing disclosed no putative pathogenic mutation in GATA4, ISLET1, and GDF1 genes. Two novel (Ile227Val, Met544Ile) and one previously reported (Glu30Gly) possibly pathogenic missense variants were identified in the ZFPM2/FOG2 gene in 3 sporadic patients of 202 (1.5%) with CTD, including 1 of 178 (0.6%) with TOF and 2 of 13 (15.4%) with DORV. Mutation analysis also detected one known missense change (Arg25Cys) in NKX2.5 gene in two (1.1%) sporadic patients with TOF. These sequence alterations were found to be absent in 500 population-matched controls. In conclusion, the present results (i) indicate and confirm that mutations in the GATA4, GDF1, and ISLET1 genes are not major determinants in the pathogenesis of TOF, (ii) provide supportive evidence of an association between ZFPM2/FOG2 gene and TOF/DORV, and (iii) provide additional examples of the possible contribution of the Arg25Cys change in the NKX2.5 to a small number of TOF cases.

Monitoring the safety of antiepileptic medication in a child with Brugada syndrome.

We report the case of an 8 year old boy presenting with episodes of decreased consciousness. As the boy's father died of a sudden cardiac death (SCD) at the age of 31 years, among other causes a Brugada syndrome (BS) was suspected. The boy was further examined at the UZ Brussels Heart Rhythm Management Center. The intravenous administration of ajmaline confirmed a BS without ventricular arrhythmias. Syncope in children can be an imminent sign of BS. BS is a life threatening condition that can deteriorate into SCD. The boy presented with episodes of lowered consciousness, transpiration and paleness. Readmission for further investigation was required. Clinical observation and continuous registered EEG during sleep showed multiple epileptical incidents. Hence the child was diagnosed with new onset epilepsy. For initiation of antiepileptic therapy, the patient was admitted at the pediatric intensive care unit (PICU). Close clinical observation and cardiovascular monitoring with continuous 12-lead ECG registration were performed during orally administered sodium valproic acid. During this anticonvulsive treatment in a child with documented BS no significant alterations in ECG-findings were observed. In this particular patient sodium valproic acid treatment can be estimated as a safe anticonvulsive therapy.

Brugada syndrome: the prognostic dilemma and value of sincope.

Since its first description in 1992 as a new clinical entity, the Brugada syndrome has stimulated great interest among physicians and basic scientists. In 2002 and 2005, two consensus conferences have respectively defined the diagnostic criteria for the syndrome. Currently the diagnosis of Brugada syndrome is based on a combination of clinical events (syncope and/or sudden cardiac death due to malignant ventricular arrhythmias) and electrocardiographic features (pathognomonic ST-segment elevation morphology). In the last years, many advances have been done in the knowledge about the genetic basis, the cellular mechanisms responsible for the typical electrocardiography features, susceptibility to ventricular arrhythmias and risk stratification. The implantable cardioverter defibrillator remains the only therapeutic option of proven efficacy for primary and secondary prophylaxis of sudden cardiac death. Identification of high risk subjects is one of the major goals in clinical decision-making. Syncope is ubiquitously recognized as a bad prognostic marker in Brugada syndrome. However, young individuals with this disease may suffer from vaso-vagal instead of arrhythmic syncope. The prognostic significance of syncope in patients with Brugada syndrome is discussed in this review.

The Brugada syndrome: update 2006.

Over the last 14 years - since the Brugada syndrome was first recognized as a distinct clinical/electrocardiographical entity - a considerable number of papers have been published on its various aspects. It has been defined as the combination of a typical ST-segment elevation in the right precordial leads and a predisposition for malignant ventricular arrhythmias occurring in the absence of structural heart disease. From the outset, controversy arose about the diagnostic criteria to be applied. This issue has been clarified since the announcement of a first (2002) and second (2005) consensus report. Our review will discuss the clinical characteristics and different possible pathophysiological mechanisms underlying the specific ECG-abnormalities and susceptibility for malignant arrhythmias. Nowadays, the main issue of discussion revolves essentially around its prognostic features, especially in asymptomatic patients. This review will compare the results of different follow-up studies and yields a possible explanation for the differences in event rates and in the identification of useful sudden-death predictors. Finally, the most recent data concerning new diagnostic techniques, gene identification and future therapeutic options will also be discussed.

[PTPN11 gene mutation in LEOPARD syndrome]. / Mutazione del gene PTPN11 nella sindrome LEOPARD.

The multiple lentigines/LEOPARD syndrome (ML/LS) is a rare and complex genetic syndrome. It is an autosomal dominant disorder with a variable expressivity. The syndrome is mainly characterised by growth retardation, multiple lentigines, and congenital heart diseases with electrocardiographic anomalies, dysmorphia of the face and deafness. The incidence of this pathology is still unknown and a familial inheritance is present in 70% of cases. Some of the ML/LS clinical features are the same as those of the Noonan syndrome (NS), such as congenital cardiac abnormalities, dysmorphia and growth retardation. NS and ML/LS are caused by allele mutations of the PTPN11 gene. We report the case of a 3-year-old girl, who was observed for the presence of widespread lentigines, a 1/6-protosystolic murmur at the mesocardium and growth retardation. The diagnosis of ML/LS was made and thus a molecular analysis of the PTPN11 gene was carried out, directly sequencing the codifying region. The molecular analysis revealed a missense mutation (A836G) in hexone 7 (TYR279CYS) of the PTPNII gene. This mutation is has been observed, at present, in a few cases of ML/LS and Noonan syndrome.

Gestión de los servicios de higiene urbana: el caso de la Ciudad de Buenos Aires, parte 3

Se presenta la tercer parte del trabajo publicado en la revista ISA en el número 70 y 71. en este caso se publican los resultados sobre el comportamiento y percepcion de la población, los indicadores de gestión , la conclusion y las recomendaciones

Gestión de los servicios de higiene urbana: el caso de la Ciudad de Buenos Aires, parte 3

Se presenta la tercer parte del trabajo publicado en la revista ISA en el número 70 y 71. en este caso se publican los resultados sobre el comportamiento y percepcion de la población, los indicadores de gestión , la conclusion y las recomendaciones

Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A.

The authors describe an Italian kindred with nine individuals affected by hyperkalaemic periodic paralysis associated with paramyotonia congenita (hyperPP/PMC). Periodic paralysis was particularly severe, with several episodes a day lasting for hours. The onset of episodes was unusually early, beginning in the first year of life and persisting into adult life. The paralytic episodes were refractory to treatment. Patients described minimal paramyotonia, mainly of the eyelids and hands. All affected family members carried the threonine to methionine substitution at codon 704 (T704M) in exon 13 of the skeletal muscle voltage gated sodium channel gene (SCN4A). The association between T704M and the hyperPP/PMC phenotype has been only recently revealed. Nevertheless, such a severe phenotype has never been reported so far in families with either hyperPP or hyperPP/PMC. These data further broaden the clinical spectrum of T704M and support the evidence that this mutation is a common cause of hyperPP/PMC.

A novel PTPN11 mutation in LEOPARD syndrome.

PTPN11 gene mutations are common to both patients with Noonan (NS) and LEOPARD syndrome (LS). So far only two recurrent mutations have been identified in LS patients by different research groups, i.e., Tyr279Cys and Thr468Met. In this work we describe the third PTPN11 mutation that has been found in a single LS patient. The mutation (c.1517A>C) substitutes a proline for a glutamine at amino acid 506 (Gln506Pro) in the phosphatase domain (PTP) of the PTPN11 peptide SHP2. This region is a mutation hotspot. Changes at amino acids 501 to 504 cause NS. Gln506Pro is predicted, by modeling analysis, to seriously disrupt the normal contacts between the regulating N-SH2 and the active PTP domains, leading to hyperactivity of the phosphatase. This report demonstrates that rarer mutations other than Tyr279Cys and Thr468Met can be found in LS patients and the need of screening the whole gene in those negative for the commonest mutations.

Role of 5-aminolevulinic acid in the diagnosis and treatment of superficial bladder cancer: improvement in diagnostic sensitivity.

OBJECTIVES: To use 5-aminolevulinic acid (5-ALA) in diagnostic cystoscopy and during transurethral resection of the bladder (TURB) to treat transitional cell carcinoma. The efficacy of this new technique was compared with standard cystoscopy. METHODS: The 5-ALA, instilled in the bladder 2 hours before cystoscopy, makes the pathologic tissue fluorescent when illuminated with blue light (375 to 400 nm). This allows a better recognition of the neoplastic forms for both diagnostic and therapeutic purposes during TURB. This method has been used since May 1997 on 49 patients in whom bladder tumor was diagnosed either immediately or during postchemotherapy follow-up. RESULTS: One hundred seventy-nine biopsies were taken of fluorescent and nonfluorescent areas (3.5 per patient) to check the effectiveness of the new method compared with standard cystoscopy. A good correlation was found between 5-ALA cystoscopy and the histopathologic diagnosis, with a good sensitivity (87%). The 5-ALA cystoscopy allowed the diagnosis of a tumor in 24 patients with negative standard cystoscopic findings. Furthermore, 5-ALA cystoscopy detected 7 cases of carcinoma in situ. Neither local nor systemic (because of endovesical instillation) side effects were noted. CONCLUSIONS: We believe that 5-ALA could be routinely used in the diagnosis of superficial bladder tumors, as it was shown to improve the diagnostic sensitivity for carcinoma in situ and to reduce the risk of recurrence related to missed cancerous lesions or incomplete TURB.