The warm-up phenomenon, described in patients with coronary artery disease, refers to the improved performance following a first exercise test. The aim of this study was to investigate the causes of the warm-up phenomenon. Fifteen patients with coronary artery disease and positive exercise test were enrolled. Patients were off treatment throughout the study. They underwent two consecutive treadmill exercise tests according to the Bruce protocol, with a recovery period of 10 min to re-establish baseline conditions. A third exercise test was then performed 2 h later. Before the onset of ischaemia, the rate-pressure product for a similar degree of workload was similar during the first and second exercise test, while it was lower during the third test (P < 0.05). Time to 1.5 mm ST-segment depression during the second and third exercise test was greater than during the first test (454 +/- 133 and 410 +/- 161 vs 354 +/- 127 s, P < 0.01, respectively). Similarly, the time to anginal pain onset was increased during the second and third exercise tests, compared to the first test (356 +/- 208 and 310 +/- 203 vs 257 +/- 204 s, P < 0.01, respectively). In contrast, rate-pressure product at 1.5 mm ST-segment depression during the second test was higher than that during the first test (232 +/- 47 vs 210 +/- 39 beats.min-1.mmHg.10(2), P < 0.01), while in the third test it was similar to that during the first (209 +/- 43 beats.min-1.mmHg.10(2), P = ns). The warm-up phenomenon observed a few minutes after exercise is characterized by an increase of both time to ischaemia and ischaemic threshold; this adaptation to ischaemia may be due to an improvement of myocardial perfusion or to preconditioning. Conversely, the warm-up phenomenon observed a few hours after repeated exercise is characterized by an increase of time to ischaemia but not of ischaemic threshold and is caused by a slower increase of cardiac workload. Thus, the mechanisms of the warm-up phenomenon may be different, time dependent and related to previous training.

Liver stiffness increases rapidly after total cavopulmonary connection and perioperative variations in some liver enzymes appear to correlate with this change. Since a true anatomical damage is known to develop gradually with Fontan circulation, early liver stiffness raise is likely due to parenchymal congestion only. Fibro-Scan can easily recognize and assess the entity of such a change. For these reasons, this diagnostic tool must be considered useful only to monitor liver stiffness changes and evolution with time, but a conventional evaluation of results, like in other acquired hepatic fibrosis, can be misleading.

OBJECTIVES Repair of Tetralogy of Fallot (TOF) has currently excellent results with either transventricular or transatrial approach. However, it is unclear as to which has better late outcomes and what role of residual pulmonary valve (PV) regurgitation in the long term is. We report on late clinical outcomes after repair in a large series of patients with TOF, focusing on the type of surgical technique. METHODS This analysis is a retrospective multicentre study on patients undergoing TOF repair in infancy. The exclusion criteria of the study were TOF with pulmonary atresia or absent PV. RESULTS We selected 720 patients who had undergone TOF repair (median age 5.7 months, interquartile range 3.7–11.7). Preoperative cyanotic spells occurred in 18%. A transatrial repair was performed in 433 (60.1%) patients. The PV was preserved in 249 (35%) patients, while the right ventricular outflow tract was reconstructed with a transannular patch (60.4%) or a conduit (4.6%) in the rest of the patients. At a median follow-up of 4 years (range 1–21, 86% complete), 10 (1.6%) patients died, while 39 (6.3%) patients required surgical reoperation and 72 (11.7%) patients required an interventional procedure. The propensity match analysis showed that the incidence of postoperative complications and adverse events at follow-up were significantly increased in patients undergoing transventricular approach repair with transannular patch (P = 0.006) and PV preservation was a significant protective factor against postoperative complications (P = 0.009, odds ratio 0.5) and late adverse events (P = 0.022). CONCLUSIONS Surgical repair of TOF in infancy is a safe procedure, with good late clinical outcomes. However, transatrial approach and PV preservation at repair are associated with lower early and late morbidity.

Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues. Based on previous studies suggesting immune senescence in DS, we hypothesized that induction of cellular senescence may contribute to early thymic involution and immune dysregulation. Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in DS patients, normally seen in older healthy subjects. Moreover, our whole transcriptomic analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased β-galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere length and integrity markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. In conclusion, our findings support the key role of cellular senescence in the pathogenesis of immune defect in DS while adding new players, such as epigenetic regulation and increased oxidative stress, to the pathogenesis of immune dysregulation.

There is no significant difference in RV volumes and function between the TA and TV. However, the TA approach seems to be protective against PV replacement in the long-term. When PV is not preserved at repair, residual pulmonary regurgitation is a significant cause of late RV dysfunction and dilation, and is associated with a higher rate of late adverse events.