Background: A landmark genome-wide association study has linked mutations in the plasma lipoprotein complex lipoprotein(a) [Lp(a)] and aortic stenosis. We attempted to determine whether Lp(a) is a key upstream mediator of aortic stenosis. Methods: Male, Lp(a) transgenic (N=10) and control mice (N=10) were fed a high cholesterol diet for 6 weeks, then hearts were sectioned for histological analysis. Human stenosis (N=8) and non-stenotic (N=7) aortic valve leaflets were obtained intraoperatively and submitted for histologic and immunohistochemical analyses. All histological sections were semi-quantitatively graded in a blinded manner (0-3/3+ units). Results: Aortic valves from Lp(a) transgenic mice fed a high-cholesterol diet demonstrated significant aortic valve changes including fibrosis (2.0/4 vs 0.5/4), calcification (1.9.4 vs 0.1/4) units, angiogenesis (1.1/4 vs 0.3/4) and inflammatory infiltration (1.0 vs 0.1/4) compared with control aortic valves (all p<0.001). Human stenotic aortic valve leaflets expressed greater Lp(a) (2.4/4 vs 1.7/4) in areas of fibrosis, inflammatory infiltration and angiogenesis, compared with non-stenotic aortic valve leaflets (p=<0.005) Conclusion: Our proof-of-concept studies offer evidence for a potential causative role of Lp(a) as a trigger of aortic stenosis. Further work is needed to confirm these results. Therapeutic strategies targeting Lp(a) levels may serve as a novel strategy to limit progressive calcification in aortic stenosis.

Deferring non-emergent cardiac surgery became the strategy of choice for several international healthcare systems afflicted by high case burdens of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) in order to both conserve valuable healthcare resources and protect patients from possible exposure. Missing from the available dataset to help guide policy development has been a clear understanding of the extent to which COVID-19 infection modulates cardiac surgery outcomes. In their investigation, Bonalumi and colleagues uncovered an inpatient COVID-19 positivity rate of almost 10 times higher than that of the general Italian population, as well as a mortality rate over 20 times higher amongst cardiac surgery patients with perioperative COVID-19 infection compared to those COVID-negative. While the summation of available evidence points to the serious consideration cardiac surgeons must give to delaying surgeries during the COVID-19 pandemic, recognition must be given to the risks that postponing cardiac surgery may have on patient outcomes. Emerging data is beginning to demonstrate the efficacy of vaccination in preventing postoperative COVID-19 infection and morbidity.

Background & Aim: Autophagy is a cytoprotective recycling mechanism, capable of digesting dysfunctional cellular components, and this process is associated with pro-survival outcomes. Autophagy may decline in the aging myocardium, thereby contributing to cardiac dysfunction. However, it remains to be established how autophagy responds to ischemia-reperfusion stress with age. Methods: Samples from the right atrium were collected from young (≤50 years; n=5) and aged (≥70 years; n=11) patients prior to and immediately following cardioplegic arrest during coronary artery bypass grafting (CABG) surgery, a model of human ischemia-reperfusion injury. Results: Mitochondrial content did not differ between the age groups, however a 32% reduction in UQCRC2 (0.74 vs 0.53, effect of age, p=0.03) was seen with age, indicating possible compositional disruptions. In response to IR, VDAC (0.75 vs 1.05, p=0.03) and COX-I protein (0.63 vs 1.10, p=0.03) was over expressed in young, but not in aged patients. Reductions in Parkin (0.95 vs 0.49, interaction effect, p=0.04) and NIX (0.60 vs 0.21, p=0.004) protein expression with age suggest an impairment in mitochondrial recycling, which may lead to an accumulation of dysfunctional mitochondria. Following IR, our data suggest that in the young cohort, autophagy is reduced as a Beclin-1 decreased by 63% (0.95 vs 0.36, p=0.001) and no changes were observed in either p62 or LC3-II:I ratio. Conclusion: Our data demonstrate a blunted cardiac mitochondrial response to ischemia with age, accompanied by a possible impairment in mitophagy. These findings support an age-associated inability of the atrial myocardium to mount appropriate adaptive responses to stress.

Background and Aim: The P2Y12 platelet receptor inhibitor ticagrelor is widely used in patients following acute coronary syndromes or in those who have received coronary stents. Bentracimab is a monoclonal antibody-based reversal agent that is being formally evaluated in a Phase 3 clinical trial. Here, we probe the knowledge, attitudes, and practice patterns of cardiac surgeons regarding their perioperative management of ticagrelor and potential application of a ticagrelor reversal agent. Methods: A questionnaire was developed by a working group of cardiac surgeons to inquire into participants’ practices and beliefs regarding ticagrelor and disseminated to practicing Canadian cardiac surgeons. Results: A total of 70 Canadian cardiac surgeons participated. Bleeding risk was identified as the most significant consideration when surgically revascularizing ticagrelor-treated patients (90%). There is variability in the duration of withholding ticagrelor prior to coronary artery bypass graft procedure in a stable patient; 44.3% wait 3 days and 32.9% wait 4 days or longer. Currently, 14.3% of cardiac surgeons prophylactically give platelet transfusions and/or fresh frozen plasma intraoperatively following protamine infusion in patients who have recently received ticagrelor. Interestingly, 47.1% of surveyed surgeons were aware of a reversal agent for ticagrelor, 91.4% of cardiac surgeons would consider utilizing a ticagrelor reversal agent if available, and 51.4% acknowledged that the introduction of such an agent would be a major advance in clinical practice. Conclusions: The present survey identified ticagrelor-related bleeding as a major concern for cardiac surgeons. Surgeons recognized the significant unmet need that a ticagrelor reversal agent would address.