PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression.

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(+/-) hearts were susceptible to AF during programmed stimulation. At short paced cycle lengths, atrial action potential durations were shorter in Pitx2c(+/-) than in wild-type. Perfusion with the ß-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(+/-) hearts, suggesting that action potential duration shortening caused wave length reduction and inducibility of AF. Expression array analyses comparing Pitx2c(+/-) 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.

Do the age of patients with tetralogy of fallot at the time of surgery and the applied surgical technique influence the reoperation rate? a single-center experience.

BACKGROUND AND PURPOSE: Primary repair of tetralogy of Fallot (TOF) has been favored in many centers for years now and results and advantages of this management seem to verify this procedure. The authors wanted to know, if the age at the time of surgery and the surgical techniques had an influence on the long-term results. PATIENTS AND METHODS: Between 1992 and 2003, 124 patients underwent complete repair of TOF at the University Hospital Münster, Germany. Patients were subdivided into two groups based on their age (< 1 year and > 1 year of age). Patients in whom a transannular patch (TAP) was used were compared with those without (NTAP), or in whom a conduit was used. RESULTS: Overall mortality was 8%, with an average age of death of 9.53 years (range 0.06-19.77 years). The patients' age at the time of surgery affected their survival as only two cases of death were reported among the group of children < 1 year of age (3.2%) whereas eight patients were older (12.9%; p = 0.0483). Six patients died within the first 30 days post surgery. Reoperation had to be performed in 21 cases, 13 (61.9%) of these patients were < 1 year of age at the time of surgery, eight were older (38.1%). A TAP, NTAP or conduit treatment did not show significant differences in long-term survival or freedom from reoperation. CONCLUSION: 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.

Influence of inflow cannula length in axial-flow pumps on neurologic adverse event rate: results from a multi-center analysis.

BACKGROUND: The application of axial-flow pumps in patients with end-stage heart failure reveals a significantly reduced infectious complication rate as compared with rates observed with pulsatile devices. The remaining adverse event rate relates mainly to thromboembolic complications with neurologic consequences. We investigated the dependence of the neurologic adverse event rate on the length of the inflow cannula. METHODS: A total of 216 consecutive patients with an axial-flow pump (INCOR; Berlin Heart GmbH, Berlin, Germany) were included in a retrospective multi-center analysis. In 138 patients, a short inflow cannula (24-mm tip length into the left ventricle), and in 78 patients a long inflow cannula (tip length 34 mm) was applied. RESULTS: Patients with a long inflow cannula (LC) demonstrated a better survival rate than those with a short inflow cannula (SC) at the end of the observation period (LC, 63.4%; SC, 52.9%; p = 0.05). The thromboembolic adverse event rate was also significantly lower. Only 3 of the 78 patients (3.8%) with an LC had a thromboembolic adverse event (thromboembolic events per patient-year = 0.11) as compared with 32 (23.2%) of SC patients (thromboembolic events per patient-year = 0.50, p < 0.001). CONCLUSIONS: Patients with a long inflow cannula had a better survival rate and a lower incidence of cerebrovascular adverse events than patients with a short inflow cannula.

Cor triatriatum: short review of the literature upon ten new cases.

Cor triatriatum is defined as a membrane within the left atrium, which might lead to restricted pulmonary venous return. Diagnosis is usually achieved by echocardiography, therapy of choice is excision of the membrane. Upon ten new cases, the association with other congenital heart diseases (CHDs), clinical symptoms and the surgical approach are discussed. Eight of ten patients were children, six of them aged<1 year. Additional CHDs included atrial and ventricular septal defects, partial anomalous pulmonary venous return and complex CHD. Surgery was performed in all cases. Prognosis is related to associated CHD.

Leukocyte activation and phagocytotic activity in cardiac surgery and infection.

BACKGROUND: Cardiac surgery (CS) using cardiopulmonary bypass (CPB) is associated with cellular and humoral defense reactions termed the systemic inflammatory response syndrome. Leukocyte activation is one of its causative mechanisms which may be aggravated by additional infection. METHODS AND RESULTS: Eighty-five patients undergoing CS with CPB were prospectively investigated. Leukocyte counts, elastase, and phagocytotic activity were measured from 24 h preoperatively up to 7 days postoperatively. Seventy-nine patients had an uneventful course (group 1) while six patients developed a systemic infection (group 2). Leukocytes and elastase levels increased postoperatively (p<0.01) and were significantly higher in group 2 (p<0.01). In both groups a decrease of leukocyte/elastase ratio occurred (p<0.002), no differences between groups were observed. The phagocytotic activity, representing the circulating cells of the reticuloendothelial system (RES), dropped on day 1 (p<0.05), and increased thereafter above baseline levels (p<0.001). No differences of RES function between groups was observed, the initial drop on day 1 in both groups was compensated by the quality of phagocytotic ability of each cells. CONCLUSION: Leukocyte activation after CS with CPB occurs. It is associated with a regular RES function and similarly leukocyte/elastase ratios in both groups, suggesting an adequate immune response. Therapeutic interventions resulting in depletion of leukocytes to alleviate reperfusion injury might impair the immune response of those patients acquiring perioperative infection and should be approached with caution. Leukocyte depletion maybe effective in patients for whom an extended period of CPB was required. Further investigations to prove this hypothesis awaits confirmation.

Successful cardiac transplantation after 4 cases of DeBakey left ventricular assist device failure.

Left ventricular assist devices (LVADs) are an established surgical therapy for patients with end-stage heart failure as a bridge to cardiac transplantation. Major disadvantages of these devices are thromboembolic events, bleeding complications, infections, and malfunctions. We report on our experiences with DeBakey LVAD malfunctions requiring LVAD exchange in 4 patients. All patients underwent subsequent cardiac transplantation and are doing well now.