Background-Intergenic variations on chromosome 4q25, close to the PITX2 transcription factor gene, are associated with atrial fibrillation (AF). We therefore tested whether adult hearts express PITX2 and whether variation in expression affects cardiac function. Methods and Results-mRNA for PITX2 isoform c was expressed in left atria of human and mouse, with levels in right atrium and left and right ventricles being 100-fold lower. In mice heterozygous for Pitx2c (Pitx2c), left atrial Pitx2c expression was 60% of wild-type and cardiac morphology and function were not altered, except for slightly elevated pulmonary flow velocity. Isolated Pitx2c ϩ/Ϫ hearts were susceptible to AF during programmed stimulation. At short paced cycle lengths, atrial action potential durations were shorter in Pitx2c ϩ/Ϫ than in wild-type. Perfusion with the ␤-receptor agonist orciprenaline abolished inducibility of AF and reduced the effect on action potential duration. Spontaneous heart rates, atrial conduction velocities, and activation patterns were not affected in Pitx2c ϩ/Ϫ hearts, suggesting that action potential duration shortening caused wave length reduction and inducibility of AF. Expression array analyses comparing Pitx2c ϩ/Ϫ with wild-type, for left atrial and right atrial tissue separately, identified genes related to calcium ion binding, gap and tight junctions, ion channels, and melanogenesis as being affected by the reduced expression of Pitx2c.Conclusions-These findings demonstrate a physiological role for PITX2 in the adult heart and support the hypothesis that dysregulation of PITX2 expression can be responsible for susceptibility to AF. (Circ Cardiovasc Genet. 2011;4:123-133.)Key Words: action potentials Ⅲ atrium Ⅲ fibrillation Ⅲ genes Ⅲ transgenic mice Ⅲ genetic predisposition A trial fibrillation (AF) is by far the most common sustained arrhythmia and causes important morbidity and mortality. 1,2 Unfortunately, the causes of the arrhythmia are not sufficiently understood to allow effective therapy to prevent AF. 3,4 Both rare and common forms of AF can be heritable, and the genes responsible may provide important clues toward therapy. Familial forms of AF associate with mutations in genes encoding sodium and potassium ion channels, connexin40, the natriuretic peptide precursor A (NPPA) but also transcription factor genes, either in candidate or genome-wide association studies. 3,[5][6][7][8] Editorial see p 105 Clinical Perspective on p 133A polymorphic locus on chromosome 4q25 (SNP rs2200733) associates with AF, particularly of early onset, in several independent studies of European and Asian populations 9,10 and conveys an approximately 1.7-fold risk of developing AF. 11 This locus is intergenic, with the gene in closest proximity being PITX2, which encodes a homeobox transcription factor of the paired type. Mutations of PITX2 are responsible for autosomal dominant anterior eye defects, including the Axenfeld-Rieger syndrome, 12 albeit without reports of AF in affected patients.During embryonic development in ...

Hypoplastic left heart syndrome (HLHS) is a challenge for the pediatric cardiologist and the surgeon. It is generally assumed that the postoperative outcome after surgery for congenital heart disease is influenced by the institutional size. We present the results of 43 patients with true HLHS (situs solitus and atrioventricular and ventriculoarterial concordance) referred for operation between 1992 and 2002 in our center. Two children had atrioseptostomy: one died soon after the operation, and the other one was transplanted successfully but died at the age of 6 months following acute rejection. The remaining 41 underwent Norwood I palliation, 21 stage II palliation, and 10 stage III palliation. Early mortality was 29% after stage I operation, 4.7% after stage II palliation, and 0% after stage III operation. Overall mortality was 39% after stage I, 9.5% after stage II, and 10% after stage III operation. Low birth weight was associated with a higher mortality (p < 0.05). Mortality declined with increasing experience, comparable to the results of very large cardiosurgical centers with many more patients. The quality of surgery and perioperative management in smaller pediatric cardiosurgical centers can reach the level of very large centers.

Heart tumours are rare, but usually life-threatening. Radical surgical resection is the therapy of choice and may offer excellent long-term survival, even in cases with malignant heart tumours.

We describe the case of a 39-year-old woman who received a self-made total artificial heart built of components from the Thoratec and ExCor Berlin Heart systems. The patient had a severe aortic/myocardial infection following replacement of the ascending aorta with a Shelhigh conduit due to type A aortic dissection. The surgical technique is described in detail in this article. This technique is feasible if a total artificial heart is not available and implantation of a biventricular assist device is not possible.

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"Panel Reactive Antibody" (PRA) testing is commonly used to assess the pretransplant antibody status in order to estimate the risk of an adverse humoral response following transplantation. We report on a female patient with end-stage cardiac failure suffering from acute myocarditis who underwent implantation of a left-ventricular assist device (Novacor, Baxter Healthcare Corp. Oakland, CA). During evaluation for heart transplantation, a PRA level of 50-70% was detected. After treatment with mycophenolate mofetil at a dosage of 2 g daily, PRA levels declined within one week to 0-5%, and remained low after discontinuation of the immunosuppressive drug. We feel that pretreatment of patients with elevated PRA levels with mycophenolate mofetil is well justified.

Early repair of TOF within the 1st year of life can be recommended, because mortality is lower than in patients treated at a higher age. There seems no significant difference in the reintervention rate between patients treated within the 1st year of life or later.