Josep Girona

IDENTIFICATION OF A GENETIC LOCUS FOR FAMILIAL ATRIAL FIBRILLATION

BACKGROUND Atrial fibrillation, the most common sustained cardiac-rhythm disturbance, affects over 2 million Americans and accounts for one third of all strokes in patients over 65 years of age. The molecular basis for atrial fibrillation is unknown, and palliative therapy is used to control the ventricular rate and prevent systemic emboli. We identified a family of 26 members of whom 10 had atrial fibrillation which segregated as an autosomal dominant disease. We subsequently identified two additional families in which the disease was linked to the same locus. METHODS We screened the human genome with 300 polymorphic dinucleotide-repeat markers using an unconventional strategy of pooling the DNA samples into two groups (affected and unaffected), which reduced the sample size by approximately 90 percent, before performing linkage analysis to map the locus. This made it possible to identify potential loci within a few weeks. RESULTS The lod scores for markers D10S569 and D10S607, located at 10q22-q24, were 3.60 in Family 1. The disease locus in Families 2 and 3 was also linked to the same markers, with lod scores of 6.02 and 5.35 for markers D10S569 and D10S607, respectively, when data on all three families were combined. Haplotype analysis of the three families showed that the locus was between D10S1694 and D10S1786, an interval of 11.3 centimorgans. CONCLUSIONS Identification of the gene for familial atrial fibrillation will help to elucidate the molecular basis of the disease and provide insights into acquired forms. The strategy of pooling DNA samples for analysis is more time and cost effective than conventional screening and should accelerate the process of gene mapping in the future.

Embarazo y cardiopatías congénitas

Introduccion y objetivos Desde la creacion de las Unidades de Cardiopatias Congenitas (CC) del Adulto y las Unidades Obstetricas de Alto Riesgo Cardiologico, ha habido creciente interes por la evolucion hemodinamica y obstetrica de embarazadas con CC. Metodos Estudio descriptivo retrospectivo de 56 mujeres con CC y media de edad de 25 (18-40) anos, que iniciaron 84 gestaciones entre enero de 1992 y agosto de 2006. Se las distribuyo en 3 grupos de riesgo gestacional: A, bajo; B, moderado y C, alto. Resultados Las incidencias de complicaciones durante la gestacion fueron del 1,6, el 15 y el 20%, y durante el puerperio, el 2, el 23 y el 50%; la mortalidad materna fue 0, del 7,6 y del 25% de los grupos A, B y C respectivamente. Nacieron 69 ninos y las tasas de prematuridad fueron del 11, el 15 y el 100% respectivamente. Los factores de riesgo principales fueron: la hipertension pulmonar (HTP), la cianosis, la arritmia, la obstruccion del tracto de salida del ventriculo izquierdo, el ventriculo derecho (VD) dilatado, el VD sistemico necesidad de y la anticoagulacion. La HTP fue el factor mas importante asociado a morbimortalidad maternofetal. Conclusiones La estratificacion por riesgo en las gestantes con CC ofrece informacion pronostica que permite adecuar la atencion de equipos multidisciplinarios para conseguir resultados exitosos.

Embolización percutánea de fístulas vasculares con el tapón vascular de Amplatzer o coils

Introduccion y objetivos Hay gran variedad de fistulas vasculares que son remitidas a los laboratorios de cateterismo cardiaco para su diagnostico y oclusion percutanea. Existe tambien una amplia gama de dispositivos utilizables en su tratamiento percutaneo. El objetivo es evaluar la utilidad, las dificultades, las complicaciones y los resultados en el tratamiento percutaneo de las fistulas vasculares mediante el uso de coils de liberacion controlada o tapones vasculares de Amplatzer. Metodos Revision retrospectiva de las embolizaciones percutaneas realizadas desde enero de 2004 a junio de 2008. Resultados Se embolizaron 51 fistulas vasculares en 30 pacientes con edades entre 6 dias y 28 anos (media, 8,4 anos), con buen resultado. Diagnosticos: 27 colaterales venosas en 16 pacientes con Glenn; 4 fistulas quirurgicas (Blalock-Taussig); 11 fistulas arteriovenosas pulmonares en 3 pacientes; 2 arterias colaterales aortopulmonares en 2 pacientes; 1 colateral venosa en 1 paciente con Fontan previo; 1 arteria aortopulmonar en un sindrome de cimitarra; 1 fistula arteriovenosa coronaria; 3 fistulas arteriovenosas sistemicas en 1 recien nacido, y una fistula entre auricula izquierda y vena cava superior tras la cirugia de un retorno venoso pulmonar anomalo. En el tratamiento percutaneo de estas lesiones se emplearon 34 tapones vasculares y 19 coils. Conclusiones Las fistulas vasculares pueden ser ocluidas percutaneamente con buen resultado. Los coils permiten el cierre de fistulas de menor diametro y los tapones vasculares estan indicados en las mas amplias. Ambos dispositivos alcanzan una alta eficacia oclusora y no se han observado especiales dificultades ni complicaciones significativas.

Percutaneous embolization of vascular fistulas using coils or Amplatzer vascular plugs.

INTRODUCTION AND OBJECTIVES A great variety of different types of vascular fistula are referred to cardiac catheterization laboratories for diagnosis and percutaneous occlusion. In addition, a wide range of devices is available for treating them percutaneously. The objectives of this study were to assess the usefulness and difficulty of treating vascular fistulas percutaneously using controlled-release coils or Amplatzer vascular plugs and to report on the complications and overall outcomes observed with these two devices. METHODS Retrospective review of percutaneous embolizations performed from January 2004 through June 2008. RESULTS In total, 51 vascular fistulas in 30 patients aged from 6 days to 28 years (mean, 8.4 years) underwent successful embolization. The underlying diagnoses were: 27 venous collaterals in 16 patients after the Glenn procedure, four surgical (i.e. Blalock-Taussig) fistulas, 11 pulmonary arteriovenous fistulas in three patients, two aortopulmonary collateral arteries in two patients, one venous collateral in a patient who underwent the Fontan procedure, one aortopulmonary artery fistula in a patient with Scimitar syndrome, one coronary arteriovenous fistula, three systemic arteriovenous fistulas in a newborn, and one fistula from the left atrium to the superior vena cava after the repair of anomalous pulmonary venous return. The lesions were treated percutaneously using 34 vascular plugs and 19 coils. CONCLUSIONS Vascular fistulas can be occluded percutaneously with good RESULTS Small fistulas can be closed using coils, while vascular plugs are preferable for large lesions. Both devices are highly effective as occluders and no particular difficulty or significant complication was observed.

Recurrent congenital heart block in neonatal lupus

Congenital heart block (CHB) is the main complication of neonatal lupus (NL) and is strongly associated with the presence of anti-SSA/Ro and anti-SSB/La antibodies. The recurrence of CHB in subsequent pregnancies in mothers with these antibodies is uncommon, occurring in approximately 15% of cases. We describe here a case of recurrent CHB in a previously asymptomatic mother with Sjögren syndrome and discuss the current strategies for the prevention and treatment of CHB in NL.

Prueba de esfuerzo con función cardiopulmonar en niños operados de cardiopatía congénita. Recomendaciones de ejercicio físico en el ámbito escolar

INTRODUCTION AND OBJECTIVES To analyze and discover if stress testing with exhaled gases in children who have had congenital heart surgery is useful so we could make physical exercise recommendations according to heart disease, type of surgery performed, present hemodynamic state and level of exercise practiced. METHODS Prospective study of 108 children, who performed stress testing with exhaled gases, electrocardiogram monitoring and blood pressure. A questionnaire was used to obtain variables concerning heart disease, surgery, present functional condition and level of exercise practiced. Exercise recommendations were given after stress testing, and after a year 35 patients answered a questionnaire. RESULTS There were significant differences between lesion severity and heart rate at rest and during effort, systolic pressure at rest and during effort, oxygen uptake, oxygen pulse, carbon dioxide production and test duration. A relationship was observed between level of weekly exercise and greater oxygen uptake and test duration, but this was not observed with the underlying heart disease. We observed that best performance occurred with fast repairing for 59 children with cyanotic heart disease. Increased exercise level was recommended for 48 children. CONCLUSIONS The cardiopulmonary function study allows us to examine the physical performance of children who have had congenital heart surgery and provides us with important data so that we can recommend better physical exercise planning.

Percutaneus double stent atrial septostomy

Graded balloon septostomy, bladed atrial septostomy, fenestrated Amplatzer devices and stent placement have been reported to obtain stable interatrial communications. We expose our favorable experience creating an interatrial septal defect, by the use of two stents concentrically placed. We think it can be a procedure to be taken into account whenever a wide interauricular septal orifice must be achieved.

Pregnancy and Congenital Heart Disease

INTRODUCTION AND OBJECTIVES Since the creation of the Adult Congenital Heart Disease Units and of the High Obstetric Risk Units, there has been increasing interest in hemodynamic and obstetric outcomes in pregnant woman with congenital heart disease. METHODS Retrospective descriptive study of 56 women with congenital heart disease aged (mean [range]) 25 (18-40) years, who experienced a total of 84 pregnancies between January 1992 and August 2006. The women were divided into three pregnancy risk groups: A, low-risk; B, moderate-risk, and C, high-risk. RESULTS The incidence of complications during pregnancy was 1.6%, 15%, and 20% in groups A, B, and C, respectively; the incidence during the puerperium was 2%, 23%, and 50%, respectively; and maternal mortality was 0%, 7.6%, and 25%, respectively. Overall, 69 children were born, and the prematurity rates in the three groups were 11%, 15%, and 100%, respectively. The following risk factors were studied: pulmonary hypertension, cyanosis, arrhythmia, left ventricular outflow tract obstruction, right ventricular dilatation, systemic right ventricle, and anticoagulation therapy. The risk factor most significantly associated with maternal or fetal morbidity or mortality was found to be pulmonary hypertension. CONCLUSIONS Risk stratification in pregnant women with congenital heart disease provides prognostic information that can help multidisciplinary teams to target care to achieve the best results.

Reversal of Hyperoxaluric Cardiomyopathy With Severe Cardiac Dysfunction After Combined Liver and Kidney Transplantation

Primary hyperoxaluria (PH) is an infrequent condition, with autosomal recessive inheritance, and consisting of abnormal oxalate metabolism with calcium depositions in the kidneys that lead to a decline in glomerular filtration rate (GFR) and progressive renal insufficiency (RI). This metabolic defect takes different forms. Type PH (PH1) is produced by an enzyme abnormality in the liver and is frequently accompanied by heart disorders caused by oxalate depositions in the cardiac tissue. Dilated cardiomyopathy has been described, with various degrees of ventricular dysfunction, stroke—due to embolization of myocardial depositions—and conduction-specific tissue abnormalities, which appear as conduction abnormalities and potentially fatal arrhythmias. Treatment of PH1 is by liver transplantation to recover the deficient enzyme activity. A 3-year-old girl (weight, 10.4 kg) of Pakistani origin, admitted for an RI study (urea, 543 mg/dL; creatinine, 11.6 mg/dL; GFR, 14.3%), was diagnosed with PH (plasma oxalate, 12.6 mg/L; urinary oxalic acid, 540.4 mmol/mol). The genetic study detected homozygosis due to a previously undescribed mutation consisting of a change in codon 164 from glutamine to arginine (p.Q164R), which codifies a nonfunctioning protein demonstrated in vitro. These findings are diagnostic of PH1. Clinically, our patient had episodes of acute lung edema related to intravenous fluid administration. Echocardiography revealed left ventricular dilatation (z-score, +4) with severe ventricular dysfunction (left ventricular ejection fraction [LVEF], 23%) (Fig. 1). Suspected dilated cardiomyopathy secondary to PH1 led to a myocardial biopsy, which showed the presence of crystals with radial striations, visible in polarized light, associated with heart disease caused by PH (Fig. 2). Given the high surgical risk of combined liver and kidney transplantation in the presence of severe ventricular dysfunction, a myocardial reserve study was performed using dobutamine stress echocardiography and following the American Heart Association protocol. This showed improved left ventricular function up to 55%-60% LVEF with dobutamine at 30 mg/kg/min but the test had to be interrupted due to a hypertensive crisis with transient neurologic symptoms. On the basis of these results and the current literature, the patient was listed for combined liver and kidney transplantation, which took place 1 month later. In the immediate postoperative period, left ventricular dilatation persisted with dysfunction (25%-30% LVEF) but subsequent follow-up showed increased myocardial thickness and progressive LVEF recovery; at 6 and 18 months post-transplantation LVEF was 68% and 71.6% respectively, with ventricular diameters normal for the patient’s age (Fig. 1). PH1 is caused by a chromosome 2 abnormality, associated with q36-37, leading to absent, decreased or dysfunctional glycolate aminotransferase enzyme hepatic activity. This abnormality leads

Extended Szabo (Anchor-Wire) Technique Concept for Stent Implantation in Congenital Heart Lesions

We report the usefulness of the Szabo (anchor-wire) technique and two modifications of such based on the same concept for stent implantation in congenital heart lesions. The modifications of the original technique are related to the localization of the cell of the stent through which the anchor wire, which stops the stent advancement, is introduced: proximal in the original technique and central or distal in the reported modifications. These techniques were performed in six patients: in two to maintain permeability of the ductus arteriosus, in three to achieve a fenestration of the interatrial septum, and in one to implant a stent in a right ventricle–to–pulmonary artery conduit close to the bifurcation. We describe the technique as well as the most important difficulties and complications encountered. The Szabo or anchor-wire technique concept is a new tool for stent implantation that can provide more accurate stent positioning compared with conventional angiographically guided implantation in different congenital heart defects. As with any new tool, this technique demands a learning curve and knowledge of potential complications.