Aortic arch shape after arch repair predicts exercise capacity: a multicentre analysis.

Aims: Coarctation of the aorta is associated with long-term morbidity including decreased exercise capacity, despite successful repair. In the absence of discrete recoarctation, the haemodynamic mechanism remains unknown. This multicentre study evaluated the relationship between aorta shape, flow, and exercise capacity in patients after arch repair, specifically through the lens of aortic size mismatch and descending aortic (DAo) flow and their association with exercise. Methods and results: Cardiac magnetic resonance, cardiopulmonary exercise test, and echocardiogram data within 1 year were analysed from 58 patients (age 28 ± 10 years, 48% male) across four centres with history of isolated arch repair. Aortic arch measurements were correlated with % predicted VO2max with subgroup analyses of those with residual arch obstruction, bicuspid aortic valve, and hypertension. Ascending aorta (AAo) to DAo diameter ratio (DAAo/DDAo) was negatively correlated with % predicted VO2max. %DAo flow positively correlated with VO2max. Sub-analyses demonstrated that the negative correlation of DAAo/DDAo with VO2max was maintained only in patients without arch obstruction and with a bicuspid aortic valve. Smaller aortic arch measurements were associated with both hypertension and exercise-induced hypertension. Conclusion: Aorta size mismatch, due to AAo dilation or small DAo, and associated decreased %DAo flow, correlated significantly with decreased exercise capacity after aortic arch repair. These correlations were stronger in patients without arch obstruction and with a bicuspid aortic valve. Aorta size mismatch and %DAo flow capture multiple mechanisms of altered haemodynamics beyond blood pressure gradient or discrete obstruction and can inform the definition of a successful repair.

Preserving the pulmonary valve in Tetralogy of Fallot repair: Reconsidering the indication for valve-sparing.

BACKGROUND: Tetralogy of Fallot (TOF) repair is a frequent procedure, and although valve-sparing (VS) repair is preferred, determining which patients can successfully undergo this operation remains controversial. We sought to identify parameters to determine a selective, accurate indication for VS repair. METHODS: We reviewed 71 patients (82%) undergoing VS repair. We analyzed hemodynamic data, intraoperative reports, and follow-up echocardiography results to identify acceptable indications. Patients requiring pulmonary valve (PV) reintervention versus no reintervention were compared. RESULTS: PV annulus size at repair was z-score of -2.0 (-5.3, 1.3). Approximately half (51%) had a z-score less than -2. Cox regression results showed this was not a risk factor for reintervention (p = .59). Overall, 1-, 3-, 5-, and 10-year freedom from PV reintervention rates were 95.8%, 92.8%, 91% and 77.8%, respectively. Residual pulmonary stenosis (PS) at initial repair was relatively higher in the reintervention group compared with no reintervention group (40 [28, 51] mmHg vs. 30 [22, 37] mmHg; p = .08). For patients with residual PS, pressure gradient (PG) was consistent over time across both groups (PV reintervention: -3 [-15, 8] mmHg vs. no reintervention: 0 [-9, 8] mmHg). The risk of PV reintervention is 3.7-fold higher when the PG from intraoperative TEE is greater than 45 mmHg (p = .04). CONCLUSIONS: Our review of the midterm outcomes of expanded indication for VS suggests intraoperative decision to convert to transannular patch is warranted if intraoperative postprocedure TEE PG is greater than 45 mmHg or RV pressure is higher than half of systemic pressure to prevent reintervention.

Pediatric aortic valve repair: Any development in the material for cusp extension valvuloplasty?

BACKGROUND: Aortic cusp extension is a technique for aortic valve (AV) repairs in pediatric patients. The choice of the material used in this procedure may influence the time before reoperation is required. We aimed to assess postoperative and long-term outcomes of patients receiving either pericardial or synthetic repairs. METHODS: We conducted a single-center, retrospective study of pediatric patients undergoing aortic cusp extension valvuloplasty (N = 38) with either autologous pericardium (n = 30) or CorMatrix (n = 8) between April 2009 and July 2016. Short- and long-term postoperative outcomes were compared between the two groups. Freedom from reoperation was compared using Kaplan-Meier analysis. Degree of aortic stenosis (AS) and aortic regurgitation (AR) were recorded at baseline, postoperatively, and at outpatient follow-up. RESULTS: At 5 years after repair, freedom from reoperation was significantly lower in the CorMatrix group (12.5%) compared to the pericardium group (62.5%) (p = .01). For the entire cohort, there was a statistically significant decrease in the peak trans-valvar gradient between preoperative and postoperative assessments with no significant change at outpatient follow-up. In the pericardium group, 28 (93%) had moderate to severe AR at baseline which improved to 11 (37%) postoperatively and increased to 21 (70%) at time of follow-up. In the biomaterial group, eight (100%) had moderate to severe AR which improved to three (38%) postoperatively and increased to seven (88%) at time of follow-up. CONCLUSION: In terms of durability, the traditional autologous pericardium may outperform the new CorMatrix for AV repairs using the cusp extension method.

Elevated levels of Interleukin (IL)-33 induce bone pathology but absence of IL-33 does not negatively impact normal bone homeostasis.

Interleukin (IL)-33 is a member of the IL-1 family. IL-33 effects are mediated through its receptor, ST2 and IL-1RAcP, and its signaling induces the production of a number of pro-inflammatory mediators, including TNFα, IL-1ß, IL-6, and IFN-γ. There are conflicting reports on the role of IL-33 in bone homeostasis, with some demonstrating a bone protective role for IL-33 whilst others show that IL-33 induces inflammatory arthritis with concurrent bone destruction. To better clarify the role IL-33 plays in bone biology in vivo, we studied IL-33 KO mice as well as mice in which the cytokine form of IL-33 was overexpressed. Mid-femur cortical bone mineral density (BMD) and bone strength were similar in the IL-33 KO mice compared to WT animals during the first 8months of life. However, in the absence of IL-33, we observed higher BMD in lumbar vertebrae and distal femur in female mice. In contrast, overexpression of IL-33 resulted in a marked and rapid reduction of bone volume, mineral density and strength. Moreover, this was associated with a robust increase in inflammatory cytokines (including IL-6 and IFN-γ), suggesting the bone pathology could be a direct effect of IL-33 or an indirect effect due to the induction of other mediators. Furthermore, the detrimental bone effects were accompanied by increases in osteoclast number and the bone resorption marker of C-terminal telopeptide collagen-I (CTX-I). Together, these results demonstrate that absence of IL-33 has no negative consequences in normal bone homeostasis while high levels of circulating IL-33 contributes to pathological bone loss.

Thermodynamics of binding by calmodulin correlates with target peptide α-helical propensity.

In this work, we have examined contributions to the thermodynamics of calmodulin (CaM) binding from the intrinsic propensity for target peptides to adopt an α-helical conformation. CaM target sequences are thought to commonly reside in disordered regions within proteins. Using the ability of TFE to induce α-helical structure as a proxy, the six peptides studied range from having almost no propensity to adopt α-helical structure through to a very high propensity. This despite all six peptides having similar CaM-binding affinities. Our data indicate there is some correlation between the deduced propensities and the thermodynamics of CaM binding. This finding implies that molecular recognition features, such as CaM target sequences, may possess a broad range of propensities to adopt local structure. Given that these peptides bind to CaM with similar affinities, the data suggest that having a higher propensity to adopt α-helical structure does not necessarily result in tighter binding, and that the mechanism of CaM binding is very dependent on the nature of the substrate sequence.