Dispersão da Refractariedade Auricular como Substrato Electrofisiológico da Vulnerabilidade Auricular em Doentes com Fibrilhação Auricular Paroxística

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.

Tratamento Cirúrgico dos Defeitos do Septo Auriculo-Ventricular. Experiência Uni-Institucional

OBJECTIVES: Atrio-ventricular septal (AVSD) defects include a variable spectrum of congenital malformations with different forms of clinical presentation. We report the surgical results, from a single institution, with this type of congenital cardiac malformation. Patients with hypoplasia of one of the ventricles were excluded from this analysis. POPULATION: Between November of 1998 and June of 2005, 49 patients with AVSD were operated on by the same team and in the same department. The average age was 37.3 months (medium 6 months) and 31 patients were female. In 38 patients (78%) an inter-ventricular communication was present (AVSD-complete) and of these, 26 were of the type A of Rastelli, being 13 of type B or C. The age for defect correction of the complete form was of 5.5 months, palliative surgery was not carried out on any of the patients. Associated lesions included: Down's syndrome in 22 patients (45%), patent arterial duct in 17 patients (35%), severe AV regurgitation in 4 patients (8%), tetralogy of Fallot in two (4%) and sub-aortic stenosis in one patient (2%). Pre-operatively 10 patients presented severe congestive heart failure and two were mechanically ventilated. RESULTS: Complete biventricular correction was carried out in all patients. The average time on bypass (ECC) was 74.1+/-17.5 min. and time of aortic clamping was 52.0+/-12.9 min. The complete defects were corrected by the double patch technique, and in all patients the mitral cleft was closed, except in two with single papillary muscle. There was no intra-operative mortality, but hospital mortality was 8%(4 patients), due to pulmonary hypertension crises, in the first 15 post-operative days. The mean ventilation time was of 36.5+/-93 hours (medium 7 h) and the average ICU stay was of 4.3+/-4.8 days (medium 3 days). The minimum follow-up period is 1 month and the maximum is 84 months (medium 29.5 months), during which time 4 re-operations (8%) took place: two for residual VSD's and two for mitral regurgitation. There was no mortality at re-do surgery. At follow up there was residual mitral regurgitation, mild in 17 patients and moderate in two. Four other patients presented with minor residual defects. CONCLUSIONS: The complete correction of AVSD can be carried out with acceptable results, in a varied spectrum of anatomic forms and of clinical severity. Despite the age of correction, for the complete forms, predominantly below 12 months, pulmonary hypertension was the constant cause for post operative mortality. Earlier timing of surgery and stricter peri-operative control might still improve results.

Assistência Ventricular em Crianças

Descreve-se a utilização de um sistema de assistência mecânica bi-ventricular, para-corpórea (Berlin Heart), como ponte para transplante, numa criança de dois anos, sofrendo de miocardiopatia dilatada. O período de assistência durou três meses e meio e o transplante foi bem sucedido. Descreve-se o caso clínico, os protocolos usados e revêem-se as indicações, as técnicas e os problemas com a assistência ventricular mecânica em crianças.

Incidência de Arritmias Ventriculares em Doentes com Disfunção Sistólica Ventricular Esquerda Grave: Existe Benefício Após Terapêutica de Ressincronização Cardíaca

Introdução: A terapêutica de ressincronização cardíaca (TRC) tem benefícios significativos em doentes seleccionados. O impacto desta modalidade na incidência de taquidisritmias ventriculares permanece controverso. Analisámos a ocorrência de terapêuticas apropriadas em doentes submetidos a TRC combinada com cardioversor-desfibrilhador (CDI). Métodos: Estudo de 123 doentes com fracção de ejecção ventricular esquerda (FEVE) < 35%, submetidos a implantação com sucesso de TRC-CDI ou CDI isoladamente (prevenção primária). Resultados: Idade média foi 63±12 anos, FEVE de 25±6%, seguimento mediano de 372 dias. Implantou-se TRC-CDI em 63 doentes (grupo A) e CDI isoladamente em 60 doentes (grupo B). No grupo A tivemos 86% de respondedores clínicos, menor prevalência de miocardiopatia isquémica(30% versus 72%), e mais doentes em classe III da NYHA antes da implantação do dispositivo(90% versus 7%) comparativamente com o grupo com CDI isoladamente. Não se identificaram diferenças relativamente à incidência de terapêuticas apropriadas (19% versus 12%) ou no tempo para a primeira terapêutica (305 dias versus 293 dias). A mortalidade total foi de 11% no grupo A e de 12% no grupo B. As curvas de Kaplan-Meier para eventos arrítmicos em doentes com TRC, não mostraram diferenças significativas (HR 3,02, IC 95% 0,82-11,09, p = NS) comparativamente com doentes sem TRC. Conclusões: Em doentes submetidos a TRC-CDI por prevenção primária, apesar da elevada taxa de respondedores, a incidência de terapêuticas apropriadas não foi diferente do obtido em doentes com CDI isoladamente.

Bloqueio Aurículo-Ventricular de Alto Grau Induzido por Angina de Prinzmetal

Apresentamos o caso de uma mulher de 46 anos com episódios frequentes de dor precordial e síncope associados a elevação do segmento ST e períodos de bloqueio aurículoventricular de alto grau transitórios. A coronariogafia excluiu lesões significativas e a doente foi tratada com nitratos e antagonistas do cálcio. Verificou-se persistência da sintomatologia associada a períodos de bloqueio aurículo-ventricular sintomáticos, refratários a otimização terapêutica. Implantação de pacemaker DDD-R. Follow-up de 4 meses sem intercorrências.

Clinical and Pathological Findings in Women with Fabry Disease

Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance. Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings. Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated glomerular filtration rate (CKD EPI equation) was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristic histologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease.

Neuroendocrine Tumours of the Female Genital Tract: a Case-Based Imaging Review with Pathological Correlation

BACKGROUND: Both primary and secondary gynaecological neuroendocrine (NE) tumours are uncommon, and the literature is scarce concerning their imaging features. METHODS: This article reviews the epidemiological, clinical and imaging features with pathological correlation of gynaecological NE tumours. RESULTS: The clinical features of gynaecological NE tumours are non-specific and depend on the organ of origin and on the extension and aggressiveness of the disease. The imaging approach to these tumours is similar to that for other histological types and the Revised International Federation of Gynecology and Obstetrics (FIGO) Staging System also applies to NE tumours. Neuroendocrine tumours were recently divided into two groups: poorly differentiated neuroendocrine carcinomas (NECs) and well-differentiated neuroendocrine tumours (NETs). NECs include small cell carcinoma and large cell neuroendocrine carcinoma, while NETs account for typical and atypical carcinoids. Cervical small cell carcinoma and ovarian carcinoid are the most common gynaecological NE tumours. The former typically behaves aggressively; the latter usually behaves in a benign fashion and tends to be confined to the organ. CONCLUSION: While dealing with ovarian carcinoids, extra-ovarian extension, bilaterality and multinodularity raise the suspicion of metastatic disease. NE tumours of the endometrium and other gynaecological locations are very rare. TEACHING POINTS: • Primary or secondary neurondocrine (NE) tumours of the female genital tract are rare. • Cervical small cell carcinoma and ovarian carcinoids are the most common gynaecological NE tumours. • Cervical small cell carcinomas usually behave aggressively. • Ovarian carcinoids tend to behave in a benign fashion. • The imaging approach to gynaecological NE tumours and other histological types is similar.

Disruption of Urate Transport in Familial Renal Glucosuria and Report on SGLT2 Expression in Normal and Pathological Kidney

Familial renal glucosuria (FRG) is a rare co -dominantly inherited benign phenotype characterized by the presence of glucose in the urine. It is caused by mutations in the SLC5A2 gene that encodes SGLT2, a Na+ -glucose co -transporter. The purpose of our current work was twofold: to characterize the molecular and phenotype findings of an FRG cohort and, in addition, to detail the SGLT2 expression in the adult human kidney. The phenotype of FRG pedigrees was evaluated using direct sequencing for the identification of sequence variations in the SLC5A2 gene. The expression of SGLT2 in the adult human kidney was studied by immunofluorescence on kidney biopsy specimens. In the absence of renal biopsies from FRG individuals, and in order to evaluate the potential disruption of SGLT2 expression in a glucosuric nephropathy, we have selected cases of nucleoside analogues induced proximal tubular toxicity. We identified six novel SLC5A2 mutations in six FRG pedigrees and described the occurrence of hyperuricosuria associated with hypouricaemia in the two probands with the most severe phenotypes. Histopathological studies proved that SGLT2 is localized to the brush -border of the proximal tubular epithelia cell and that this normal pattern was found to be disrupted in cases of nucleoside analogues induced tubulopathy. We present six novel SLC5A2 mutations, further contributing to the allelic heterogeneity in FRG, and identified hyperuricosuria and hypouricaemia as part of the FRG phenotype. SGLT2 is localized to the brush -border of the proximal tubule in the adult human normal kidney, and aberrant expression of the co -transporter may underlie the glucosuria seen with the use of nucleoside analogues.

Time to Left Ventricular Reverse Remodeling after Cardiac Resynchronization Therapy: Better Late than Never

INTRODUCTION: Left ventricular reverse remodeling (LVRR), defined as reduction of end-diastolic and end-systolic dimensions and improvement of ejection fraction, is associated with the prognostic implications of cardiac resynchronization therapy (CRT). The time course of LVRR remains poorly characterized. Nevertheless, it has been suggested that it occurs ≤6 months after CRT. OBJECTIVE: To characterize the long-term echocardiographic and clinical evolution of patients with LVRR occurring >6 months after CRT and to identify predictors of a delayed LVRR response. METHODS: A total of 127 consecutive patients after successful CRT implantation were divided into three groups according to LVRR response: Group A, 19 patients (15%) with LVRR after >6 months (late LVRR); Group B, 58 patients (46%) with LVRR before 6 months (early LVRR); and Group C, 50 patients (39%) without LVRR during follow-up (no LVRR). RESULTS: The late LVRR group was older, more often had ischemic etiology and fewer patients were in NYHA class ≤II. Overall, group A presented LVRR between group B and C. This was also the case with the percentage of clinical response (68.4% vs. 94.8% vs. 38.3%, respectively, p<0.001), and hospital readmissions due to decompensated heart failure (31.6% vs. 12.1% vs. 57.1%, respectively, p<0.001). Ischemic etiology (OR 0.044; p=0.013) and NYHA functional class