The impact of sex on pathophysiological processes, clinical presentation, treatment options, as well as outcomes of degenerative aortic stenosis remain poorly understood. Female patients are well represented in transfemoral aortic valve implantation (TAVI) trials and appear to derive favorable outcomes with TAVI. However, higher incidences of major bleeding, vascular complications, and stroke have been reported in women following TAVI. The anatomical characteristics and pathophysiological features of aortic stenosis in women might guide a tailored planning of the percutaneous approach. We highlight whether a sex‐based TAVI management strategy might impact on clinical outcomes. This review aimed to evaluate the impact of sex from diagnosis to treatment of degenerative aortic stenosis, discussing the latest evidence on epidemiology, pathophysiology, clinical presentation, therapeutic options, and outcomes. Furthermore, we focused on technical sex‐oriented considerations in TAVI including the preprocedural screening, device selection, implantation strategy, and postprocedural management.

Background The prognostic implications of cardiac procedural myocardial injury and infarction (MI) in chronic coronary syndrome patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Objective To determine the optimal cardiac troponin threshold for identifying prognostically important events. Methods Using a pooled dataset of nine registries and one randomized trial, we analysed individual data of 14,433 patients undergoing elective PCI with a normal or moderately elevated baseline pre-PCI cardiac troponin (cTn). A multivariate model was performed to evaluate the associations between post-PCI cTn elevation and 1-year mortality after PCI, including thresholds used by existing procedural myocardial injury definitions (Fourth Universal Definition of MI [UDMI] and Academic Research Consortium 2 [ARC-2] / Society for Cardiovascular Angiography and Interventions (SCAI)). The association between type 4a MI and 1-year mortality was also evaluated. Results Procedural myocardial injury defined by the Fourth UDMI occurred in 52.5% of patients and was not associated with 1-year mortality (adjOR 1.27, 95% CI [0.90–1.81] p=0.18). The association between post-PCI cTn elevation and 1-year mortality was significant above a 3-fold increase above the upper reference limit, and was optimal for a 5.2-fold increase which corresponded to an 18.3% rate of event, and an adjOR of 2.03 (95% CI [1.31–3.14], p=0.002) (figure). Procedural myocardial injury defined by the ARC-2/SCAI definition occurred in 1.3% of the patients, had a strong association with 1-year mortality (adjOR 4.15, 95% CI [1.62–10.64], p<0.01) but lacked sensitivity (5.2% sensitivity). Type 4a MI occurred in 12.7% of patients, was strongly associated with 1-year mortality (adjOR 3.18, 95% CI [1.47–6.90], p=0.002), but could only be evaluated in a subset of patients (n=3 084) with available data on new myocardial ischaemia post-PCI. Conclusions We have demonstrated that a post-PCI cTn elevation ≥5x the 99th percentile URL in CCS patients with normal baseline cTn, represents the optimal threshold for defining prognostically important or “Major” procedural myocardial injury in the absence of evidence for new myocardial ischaemia. Major procedure related myocardial injury and type 4a MI should be considered as a quality metric and endpoints in clinical trials. Adjusted OR of mortality at 1 year Funding Acknowledgement Type of funding source: None

Background Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) are physiological parameters to assess coronary microvascular dysfunction. CFR and MRR can be assessed using bolus or continuous thermodilution, and the correlation between these methods has not been clarified. Furthermore, their association with angina and quality of life is unknown. Methods and Results In total, 246 consecutive patients with angina and nonobstructive coronary arteries from the multicenter Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL‐CFT) were investigated. The 36‐item Short Form Health Survey Quality of Life and Seattle Angina questionnaires were completed by 153 patients before the invasive measurements. CFR and MRR were measured consecutively with bolus and continuous thermodilution. Mean continuous thermodilution‐derived coronary flow reserve (CFR abs ) was significantly lower than mean bolus thermodilution‐derived coronary flow reserve (CFR bolus ) (2.6±1.0 versus 3.5±1.8; P <0.001), with a modest correlation ( ρ =0.305; P <0.001). Mean continuous thermodilution‐derived microvascular resistance reserve (MRR abs ) was also significantly lower than mean bolus thermodilution‐derived MRR (MRR bolus ) (3.1±1.1 versus 4.2±2.5; P <0.001), with a weak correlation ( ρ =0.280; P <0.001). CFR bolus and MRR bolus showed no correlation with any of the angina and quality of life domains, whereas CFR abs and MRR abs showed a significant correlation with physical limitation ( P =0.005, P =0.009, respectively) and health ( P =0.026, P =0.012). In a subanalysis in patients in whom spasm was excluded, the correlation further improved (MRR abs versus physical limitation: ρ =0.363; P =0.041, MRR abs versus physical health: ρ =0.482; P =0.004). No association with angina frequency and stability was found. Conclusions Absolute flow measurements using continuous thermodilution to calculate CFR abs and MRR abs weakly correlate with, and are lower than, the surrogates CFR bolus and MRR bolus . Absolute flow parameters showed a relationship with physical complaints. No relationship with angina frequency and stability was found.

Background Invasive coronary function testing (CFT), including both acetylcholine (ACH) spasm provocation testing and assessment of coronary flow and resistance, is recommended to assess coronary vasomotor dysfunction (CVDys) in patients with angina and non-obstructive coronary artery disease (ANOCA). Objectives To determine repeat testing reliability of invasive measurements of CVDys. Methods In the EDIT-CMD trial, 73 patients underwent both baseline and follow-up CFT after six weeks. Repeat testing reliability for CVDys assessment, including coronary flow reserve (CFR), index of microvascular resistance (IMR), absolute flow (Q) and microvascular resistance (R) was assessed by 1.) comparing continuous values between baseline and follow-up measurement, including difference and correlation between the two measurements 2.) classification agreement (CCA) for the presence of CMD according to cut-offs, which was also assessed for ACH spasm provocation test and 3.) Bland-Altman plots. Fisher-Z scores were used to compare correlations. Results Mean CFR was 3.1±1.5 at baseline and 4.1±1.5 at follow-up (P=0.03), with no significant correlation (ρ=0.285, P=0.10). Mean IMR was 27±12 at baseline and 27±19 at follow-up (P=0.94), with a trend to a significant correlation (ρ=0.312, P=0.07). The CCA between the baseline and follow-up was 74% for CFR and 57% for IMR. Mean Q was 183±72 at baseline and 192±78 at follow-up (P=0.49), with a significant correlation (ρ=0.579, P&lt;0.001). Mean R was 527±233 at baseline and 506±228 at follow-up (P=0.67), with a significant correlation (ρ=0.51, p=0.03). The CCA between R at baseline and 6 weeks follow-up was 72% and for Q this was 82%. The correlation coefficient (ρ) of Q was significantly better than the ρ of CFR (P=0.006). The ρ of R and IMR did not differ. For the ACH spasm provocation test we found a CCA of 79% between both measurements. Conclusion This is the first study to assess re-test reliability of the invasive CFT. Measurements of Q and R show higher agreement and correlation than their surrogates CFR and IMR in assessing microvascular function. ACH provocation spasm test also demonstrated good re-test reliability. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

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