There has been conflicting clinical evidence as to the influence of female sex on outcomes after transcatheter aortic valve replacement.
The aim of this study was to evaluate the impact of sex on ...early and late mortality and safety end points after transcatheter aortic valve replacement using a collaborative meta-analysis of patient-level data.
From the MEDLINE, Embase, and the Cochrane Library databases, data were obtained from 5 studies, and a database containing individual patient-level time-to-event data was generated from the registry of each selected study. The primary outcome of interest was all-cause mortality. The safety end point was the combined 30-day safety end points of major vascular complications, bleeding events, and stroke, as defined by the Valve Academic Research Consortium when available.
Five studies and their ongoing registry data, comprising 11,310 patients, were included. Women constituted 48.6% of the cohort and had fewer comorbidities than men. Women had a higher rate of major vascular complications (6.3% vs. 3.4%; p < 0.001), major bleeding events (10.5% vs. 8.5%; p = 0.003), and stroke (4.4% vs. 3.6%; p = 0.029) but a lower rate of significant aortic incompetence (grade ≥2; 19.4% vs. 24.5%; p < 0.001). There were no differences in procedural and 30-day mortality between women and men (2.6 % vs. 2.2% p = 0.24 and 6.5% vs. 6.5% p = 0.93, respectively), but female sex was independently associated with improved survival at median follow-up of 387 days (interquartile range: 192 to 730 days) from the index procedure (adjusted hazard ratio: 0.79; 95% confidence interval: 0.73 to 0.86; p = 0.001).
Although women experience more bleeding events, as well as vascular and stroke complications, female sex is an independent predictor of late survival after transcatheter aortic valve replacement. This should be taken into account during patient selection for this procedure.
The purpose of this study was to develop an adenosine-independent, pressure-derived index of coronary stenosis severity.
Assessment of stenosis severity with fractional flow reserve (FFR) requires ...that coronary resistance is stable and minimized. This is usually achieved by administration of pharmacological agents such as adenosine. In this 2-part study, we determine whether there is a time when resistance is naturally minimized at rest and assess the diagnostic efficiency, compared with FFR, of a new pressure-derived adenosine-free index of stenosis severity over that time.
A total of 157 stenoses were assessed. In part 1 (39 stenoses), intracoronary pressure and flow velocity were measured distal to the stenosis; in part 2 (118 stenoses), intracoronary pressure alone was measured. Measurements were made at baseline and under pharmacologic vasodilation with adenosine.
Wave-intensity analysis identified a wave-free period in which intracoronary resistance at rest is similar in variability and magnitude (coefficient of variation: 0.08 ± 0.06 and 284 ± 147 mm Hg s/m) to those during FFR (coefficient of variation: 0.08 ± 0.06 and 302 ± 315 mm Hg s/m; p = NS for both). The resting distal-to-proximal pressure ratio during this period, the instantaneous wave-free ratio (iFR), correlated closely with FFR (r = 0.9, p < 0.001) with excellent diagnostic efficiency (receiver-operating characteristic area under the curve of 93%, at FFR <0.8), specificity, sensitivity, negative and positive predictive values of 91%, 85%, 85%, and 91%, respectively.
Intracoronary resistance is naturally constant and minimized during the wave-free period. The instantaneous wave-free ratio calculated over this period produces a drug-free index of stenosis severity comparable to FFR. (Vasodilator Free Measure of Fractional Flow Reserve ADVISE; NCT01118481).
Summary Background The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were ...powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. Methods We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. Findings Of 43 904 patients recruited in 26 trials of DES, 11 557 (26·3%) were women (mean age 67·1 years SD 10·6). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 18·6% women in the bare-metal stent group, 294 7·8% in the early-generation DES group, and 330 6·3% in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. Interpretation The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. Funding Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.
Background
The prevalence of both chronic kidney disease (CKD) and aortic stenosis (AS) increase with age. Although baseline CKD is frequent in patients undergoing transcatheter aortic valve ...replacement (TAVR), its significance among women is largely unknown.
Methods
Women's INternational Transcatheter Aortic Valve Implantation (WIN‐TAVI) is a multinational, prospective registry of women undergoing TAVR for severe AS. We included patients with available baseline estimated glomerular filtration rate (eGFR) and completed 1‐year follow‐up. Patients were categorized into three groups based on their eGFR: No CKD (normal kidney function to stage 2 CKD: eGFR ≥60 ml/min/1.73 m2); (b) mild CKD (stage 3a CKD: eGFR = 45–59 ml/min/1.73 m2); and (c) moderate/severe CKD (stage ≥3b CKD: eGFR <45 ml/min/1.73 m2). All events were adjudicated according to the Valve Academic Research Consortium (VARC)‐2 criteria.
Result
Out of 852 women undergoing TAVR, 326 (38.3%) had no CKD, 225 (26.4%) had mild CKD, and 301 (35.3%) had moderate/severe CKD. Women with higher stage of CKD at baseline were more likely to have a history of hypertension, diabetes, atrial fibrillation, anemia, chronic lung disease, hemodialysis, prior percutaneous coronary intervention, and pacemaker implantation. After multivariate adjustment, moderate/severe CKD was associated with a greater risk of 1‐year VARC‐2 safety endpoints hazard ratio (HR) 1.68, 95% confidence interval (CI): 1.10–2.60, all‐cause death (HR 2.00, 95% CI: 1.03–3.90), and composite of death, myocardial infarction, stroke or life‐threatening bleeding (HR 1.70, 95% CI: 1.04–2.76). There were no differences in 30‐day and 1‐year VARC‐2 efficacy and 30‐day VARC‐2 safety outcomes.
Conclusion
CKD is associated with substantial and independent risk for mortality and morbidity at 1‐year follow‐up in women undergoing TAVR.
This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses.
The instantaneous wave-free ratio (iFR) is a vasodilator-free ...pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR.
In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration iFRa), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms.
When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48).
iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR.
The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to ...quantify how often iFR pullback alters PCI strategy in real-world clinical settings.
In tandem and diffuse disease, offline analysis of continuous iFR pullback measurement has previously been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the online analysis approach (iFR pullback) remains untested.
Angiographically intermediate tandem and/or diffuse lesions were entered into the international, multicenter iFR GRADIENT (Single instantaneous wave-Free Ratio Pullback Pre-Angioplasty Predicts Hemodynamic Outcome Without Wedge Pressure in Human Coronary Artery Disease) registry. Operators were asked to submit their procedural strategy after angiography alone and then after iFR-pullback measurement incorporating virtual PCI and post-PCI iFR prediction. PCI was performed according to standard clinical practice. Following PCI, repeat iFR assessment was performed and the actual versus predicted post-PCI iFR values compared.
Mean age was 67 ± 12 years (81% male). Paired pre- and post-PCI iFR were measured in 128 patients (134 vessels). The predicted post-PCI iFR calculated online was 0.93 ± 0.05; observed actual iFR was 0.92 ± 0.06. iFR pullback predicted the post-PCI iFR outcome with 1.4 ± 0.5% error. In comparison to angiography-based decision making, after iFR pullback, decision making was changed in 52 (31%) of vessels; with a reduction in lesion number (-0.18 ± 0.05 lesion/vessel; p = 0.0001) and length (-4.4 ± 1.0 mm/vessel; p < 0.0001).
In tandem and diffuse coronary disease, iFR pullback predicted the physiological outcome of PCI with a high degree of accuracy. Compared with angiography alone, availability of iFR pullback altered revascularization procedural planning in nearly one-third of patients.
The study sought to examine the safety and performance of transcatheter aortic valve replacement (TAVR) using an all-female registry and to further explore the potential impact of female sex-specific ...characteristics on clinical outcomes after TAVR.
Although women comprise 50% of patients with symptomatic severe aortic stenosis undergoing TAVR, the optimal treatment strategy remains undetermined.
The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry is a multinational, prospective, observational registry of women undergoing TAVR for aortic stenosis, conducted without any external funding. The primary endpoint was the Valve Academic Research Consortium (VARC)-2 early safety endpoint at 30 days (composite of mortality, stroke, major vascular complication, life-threatening bleeding, stage 2 or 3 acute kidney injury, coronary artery obstruction, or repeat procedure for valve-related dysfunction).
Between January 2013 and December 2015, 1,019 women were enrolled across 19 European and North American centers. The mean patient age was 82.5 ± 6.3 years, mean EuroSCORE I was 17.8 ± 11.7% and mean Society of Thoracic Surgeons score was 8.3 ± 7.4%. TAVR was performed via transfemoral access in 90.6% and new-generation devices were used in 42.1%. In more than two-thirds of cases, an Edwards SAPIEN 23 mm (Edwards Lifesciences, Irvine, California) or Medtronic CoreValve ≤26 mm (Medtronic Inc., Minneapolis, Minnesota) device was implanted. The 30-day VARC-2 composite endpoint occurred in 14.0% with 3.4% all-cause mortality, 1.3% stroke, 7.7% major vascular complications, and 4.4% VARC life-threatening bleeding. The independent predictors of the primary endpoint were age (odds ratio OR: 1.04; 95% confidence interval CI: 1.00 to 1.08), prior stroke (OR: 2.02; 95% CI: 1.07 to 3.80), left ventricular ejection fraction <30% (OR: 2.62; 95% CI: 1.07 to 6.40), new device generation (OR: 0.59; 95% CI: 0.38 to 0.91), and history of pregnancy (OR: 0.57; 95% CI: 0.37 to 0.85).
Women enrolled in this first ever all-female TAVR registry with collection of female sex-specific baseline parameters, were at intermediate-high risk and experienced a 30-day VARC-2 composite safety endpoint of 14.0% with a low incidence of early mortality and stroke. Randomized assessment of TAVR versus surgical aortic valve replacement in intermediate risk women is warranted to determine the optimal strategy.
The comparative performance of different drug-eluting stents (DES) among female patients has not been assessed in a randomized manner.
The SPIRIT Women Clinical Evaluation trial compared the durable ...polymer everolimus-eluting XIENCE stent (DP-EES) with the durable polymer sirolimus-eluting Cypher stent (DP-SES) in women undergoing percutaneous coronary intervention (PCI).
A total of 455 female patients with stable CAD were randomly assigned to receive DP-EES (n = 304) or DP-SES (n = 151). The powered angiographic outcome of the trial was in-stent late lumen loss (LLL) at 9 months after the index procedure. Secondary angiographic end points included in-segment LLL, in-stent and in-segment binary restenosis and percent diameter stenosis. The primary clinical outcome was a composite of all-cause death, myocardial infarction (MI) or target vessel revascularization (TVR).
At 9-month follow-up, in-stent LLL was 0.19±0.38 mm and 0.11±0.37 mm in patients assigned to DP-EES and DP-SES, respectively. The one-sided upper 95% CI of the difference in in-stent LLL between the groups of 0.08 mm was 0.15 and therefore within the pre-specified non-inferiority margin of 0.17 mm (p for non-inferiority = 0.013). However, the test for superiority showed a borderline significant difference in terms of LLL between DP-EES and DP-SES (p for superiority = 0.044). There were no significant differences in binary restenosis (2.0% vs. 0.72%, p = 0.44) and percent diameter stenosis (14.97±12.17 vs. 13.36±10.82, p = 0.19). The rate of definite stent thrombosis at 12 months was lower in patients treated with DP-EES (0% vs. 2.0%, p = 0.036).
Among women undergoing PCI, DP-EES was associated with a small but probably clinically relevant increase in in-stent LLL at 9 months as compared to DP-SES and with a lower risk of definite stent thrombosis at 12 months.
ClinicalTrials.gov NCT01182428. https://clinicaltrials.gov/.
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