Feasibility of transcaval access TAVI in morbidly obese patients: A single-center experience.

OBJECTIVES: We report a single-center experience in utilizing the transcaval-access transcatheter aortic valve implantation (TAVI) as an alternative approach in morbidly obese patients. BACKGROUND: Morbidly obese patients present frequently for TAVI. Transfemoral arterial access TAVI in these patients is technically challenging due to deep arterial access, resulting in a higher risk of vascular complications. Transcaval access TAVI is increasingly used in patients with prohibitive iliofemoral arterial access. METHODS: We used the transcaval approach for eight morbidly obese patients who had otherwise technically feasible femoral arterial access. This technique provides an alternative arterial access point that potentially circumvents some of the challenges relating to femoral arterial access. RESULTS: We report eight morbidly obese patients with a mean body mass index of 42.3 ± 6.2 kg/m2 who underwent transcaval access TAVI at our center (mean EuroScore II 2.47 ± 1.83%). The patient mean age was 70.3 ± 9.8 years; six were female. All eight patients underwent a successful and uncomplicated procedure. The median time to discharge was 2 days and all patients were alive at 30 days. CONCLUSIONS: Transcaval access TAVI is a feasible alternative for morbidly obese patients and may reduce vascular complications. Further data are required to evaluate the safety of this approach.

Mobility aids predict mortality after transcatheter aortic valve implantation.

BACKGROUND: Selection of appropriate patients for transcatheter aortic valve implantation (TAVI) can be challenging. Many factors can influence post-procedure outcomes. Traditional surgical scoring systems do not discriminate effectively. Medical parameters and functional indices can characterize mortality risk. Mobility is an important predictive functional index but is largely defined using subjective criteria. AIM: To describe the relationship between mobility, objectively defined by the requirement for gait aids to ambulate, and all-cause 30-day and long-term mortality in patients undergoing TAVI. METHODS: Mobility aid use was assessed in 1444 consecutive patients undergoing TAVI in a single center. Patients were categorized into "unaided," "1-stick," and "higher aid" groups based on the Brighton Mobility Index. Mortality tracking was obtained via the NHS Spine Portal in February 2021. RESULTS: Patients were aged 82 (IQR 78-86). 66% of patients walked unaided, 26% walked with 1 stick, and 8% required more assistance (e.g., 2 sticks, a Rollator, a Zimmer frame, or a wheelchair). Overall 30-day mortality for the whole cohort was 3.5%; 1-year mortality was 12.2%. Mobility was a significant predictor of 30-day mortality (p = 0.025). Use of a higher aid was associated with a mortality odds ratio of 2.83 (95% CI: 1.39-5.74). Mobility was also a significant predictor of long-term mortality (p < 0.001). Odds ratios for 1-stick and higher aid groups were 1.45 (95% CI: 1.21-1.72) and 2.01 (95% CI: 1.55-2.60), respectively. CONCLUSION: Objective assessment of mobility by gait aid use predicts both short and long-term survival in patients undergoing TAVI. Increased dependence on mobility aids is associated with a worse prognosis.

Prosthesis Geometrical Predictors of Leaflet Thrombosis Following Transcatheter Aortic Valve Replacement With Intra-Annular Prostheses.

OBJECTIVE: To determine the association between prosthesis geometry with leaflet thrombosis (LT). BACKGROUND: Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) is a recognised entity. The association between prosthesis geometry with LT is unclear but maybe a potential modifiable factor in its prevention. METHODS: Patients who received an intra-annular TAVR prosthesis and were prospectively planned to undergo post-procedural computed tomography (CT) imaging were included. Leaflet thrombosis was defined as at least 50% restricted leaflet motion on CT. Prosthesis expansion and eccentricity was measured at prosthesis inflow, annulus and outflow levels. Prosthesis misalignment was defined as the average angle deviation between native and prosthesis leaflet commissure, greater than 30°. RESULTS: Prevalence of LT was 13.7% in 117 patients. None of the patients with LT were on anticoagulation therapy. Patients with LT had reduced prosthesis annular expansion (89.4±5.2% vs 97.0±4.4%, p<0.01), greater prosthesis misalignment (81.3% vs 48.5%, p=0.02) and deeper implants (6.3±1.7 mm vs 4.3±1.5 mm, p<0.01). Threshold for the presence of LT on ROC analysis was an implant depth of 5.7 mm (AUC [area under curve]=0.81). Independent predictors of LT were annular under-expansion (Odds ratio [OR] 1.4, 95% confidence interval [CI] 1.2-1.7, p=0.03) prosthesis misalignment (OR 6.8, 95%CI 1.1-45.5, p=0.04) and implant depth (OR 1.9, 95%CI 1.1-3.2, p=0.03). Anticoagulation therapy was a protective factor (OR 0.2; 95%CI 0.1-0.4, p<0.01). CONCLUSION: Geometrical predictors of LT post intra-annular TAVR were reduced prosthesis expansion at the annular level, lower implant depth and greater prosthesis misalignment. These factors may be important considerations during procedural planning for TAVR.

Clinical predictors and sequelae of computed tomography defined leaflet thrombosis following transcatheter aortic valve replacement at medium-term follow-up.

BACKGROUND: The clinical predictors and sequelae of leaflet thrombosis (LT) following transcatheter aortic valve replacement (TAVR) is still unclear. Therefore, our aim was to determine the clinical predictors and sequelae at mid-term follow-up of computed tomography (CT)-defined LT following TAVR. METHODS AND RESULTS: We performed a prospective evaluation with a 320-multislice CT following TAVR for the presence of LT, defined as hypo-attenuated leaflet thickening (HALT). Four-dimensional CT image-rendering was performed to determine the presence of reduced leaflet motion (RELM). 172 patients [89 (51.7%) male, mean age 82.8 ± 5.7 years] treated with commercially available TAVR device (Lotus 54%, CoreValve 32% and Sapien 3 14%) were included, with median CT-scan at 6.0 weeks post-TAVR. Prevalence of HALT was 14.0% (24 cases) and RELM was 9.8% (17 cases). On multivariate analysis, patients with HALT were less prescribed oral anticoagulation (OAC) (OR 9.9), received larger TAVR prostheses (OR 5.7) and higher rates of moderate-severe para-valvular regurgitation (PVR) (OR 16.3). There was no difference in clinical outcomes at a median follow-up of 2.3 years. Patients with RELM had significantly higher transvalvular gradients after discharge when compared to those without RELM. CONCLUSIONS: Absence of OAC, large TAVR prostheses and moderate-severe PVR were predictors for LT. Transvalvular gradients were higher in patients that developed RELM but not HALT. Further studies are warranted to determine the long-term impact of LT on TAVR durability. Prevalence of different sub-types of CT-defined LT (HALT and RELM) and the clinical predictors of developing LT following TAVR. CT computed tomography, HALT hypo-attenuated leaflet thickening, LT leaflet thrombosis, RELM reduced leaflet motion, TAVR transcatheter aortic valve replacement.

Fractional Flow Reserve following Percutaneous Coronary Intervention.

Fractional flow reserve (FFR) is routinely used to determine lesion severity prior to percutaneous coronary intervention (PCI). However, there is an increasing recognition that FFR may also be useful following PCI to identify mechanisms leading to restenosis and the need for repeat revascularization. Post-PCI FFR is associated with the presence and severity of stent under-expansion and may help identify peri-stent-related complications. FFR pullback may also unmask other functionally significant lesions within the target vessel that were not appreciable on angiography. Recent studies have confirmed the prognostic utility of performing routine post-PCI FFR and suggest possible interventional targets that would improve stent durability. In this review, we detail the theoretical basis underlying post-PCI FFR, provide practical tips to facilitate measurement, and discuss the growing evidence supporting its use.

Application of the DILEMMA score to improve lesion selection for invasive physiological assessment.

OBJECTIVES: We sought to assess the validity of the DILEMMA score against instantaneous wave-free ratio (iFR) and evaluate its utility in rationalizing the number of patients referred for invasive physiological assessment. BACKGROUND: The DILEMMA score is a validated angiographic scoring tool incorporating minimal lumen diameter, lesion length and subtended myocardial area that has been shown to predict the functional significance of lesions as assessed by fractional flow reserve (FFR). METHODS: Patients in the DEFINE-FLAIR study who had coronary stenosis of intermediate severity were randomized to either FFR or iFR. DILEMMA score was calculated retrospectively on a subset of this cohort by operators blinded to FFR or iFR values. RESULTS: Three hundred and forty-six lesions (181 assessed by FFR; 165 by iFR) from 259 patients (mean age 66.0 years, 79% male) were included. A DILEMMA score ≤ 2 had a negative predictive value of 96.3% and 95.7% for identifying lesions with FFR >0.80 and iFR >0.89, respectively. A DILEMMA score ≥ 9 had a positive predictive value of 88.9% and 100% for identifying lesions with FFR ≤0.80 and iFR ≤0.89, respectively. The receiver operating characteristic area under the curve values for DILEMMA score to predict FFR ≤0.80 and iFR ≤0.89 were 0.83 (95% CI 0.77-0.90) and 0.82 (0.75-0.89) respectively. A DILEMMA score ≤ 2 or ≥9 occurred in 172 of the 346 lesions (49.7%). CONCLUSIONS: Using DILEMMA score in patients with coronary stenosis of intermediate severity may reduce the need for pressure wire use, offering potential cost-savings and minimizing the risks associated with invasive physiological lesion assessment.

The Role of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Measurements in Patients with Acute Coronary Syndrome.

PURPOSE OF REVIEW: The role of fractional flow reserve to guide revascularization in patients with stable angina is well established. The instantaneous wave-free ratio (iFR) is an emerging adenosine-free resting index that is non-inferior to FFR and has potential to streamline the functional evaluation of coronary artery disease. The feasibility and utility of intracoronary physiology in patients with acute coronary syndrome (ACS) is unclear. This review will discuss the physiological principles and validity of using FFR and iFR in patients presenting with ACS. We will also provide an overview of the available evidence for their role in guiding revascularization in this patient group. RECENT FINDINGS: The use of intracoronary physiology in culprit lesions of patients presenting with STEMI is not recommended and its accuracy is uncertain in patients with NSTEMI. In contrast, the physiological assessment of non-culprit vessels with FFR and IFR is a reliable measure of lesion-specific ischemia. Recent studies have demonstrated that FFR-guided revascularization of non-culprit lesions improves clinical outcomes although the role of iFR in this patient cohort is unknown. Physiology-guided revascularization of non-culprit ACS lesions improves clinical outcomes. Future studies investigating the complementary role of plaque morphology, biomechanics, and systemic inflammation may provide clinicians with a more comprehensive framework to guide treatment decisions.

"Liver or Let Die": Percutaneous PFO Closure Through Hepatic Vein Access.

A 73-year-old farmer presented with platypnoea-orthodeoxia syndrome (POS). A transoesophageal echocardiogram (TOE) disclosed a patent foramen ovale (PFO) with significant right-to-left shunt on assuming upright posture. An initial attempt at PFO closure through the femoral vein was abandoned due to a completely occluded inferior vena cava. A second attempt through the internal jugular vein was also unsuccessful due to the steep angulation between superior vena cava and septum primum flap. Because of disabling symptoms, an attempt through a hepatic vein (HV) was scheduled and performed under general anaesthesia with TOE guidance. Ultrasound-guided access through an intercostal window to a peripheral HV was performed and the position confirmed with contrast injections. The PFO was easily crossed with a glide wire which was exchanged to a stiffer guide wire. A 25mm closure device was successfully deployed across the PFO. After retrieval of the delivery system, haemostasis of the HV was attained with a contrast-guided Gelfoam (Pfizer, New York, NY, USA) injection. Unfortunately, the patient had to undergo subsequent emergency coiling to an iatrogenically injured hepatic artery branch leading to full recovery and significant clinical improvement. Subsequent echocardiography demonstrated a well-positioned device with no residual shunt. This case illustrates that percutaneous PFO closure through a HV is a feasible procedure and should be considered in anatomy that is otherwise prohibitive for conventional approach. Extra care should be taken with initial vascular access into the HV and final haemostasis of the access site.

Impact of commissural versus coronary alignment on risk of coronary obstruction following transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) with commissural alignment aims to limit the risk of coronary occlusion and maintain good coronary access. However, due to coronary origin eccentricity within the coronary cusp, coronary-commissural overlap (CCO) may still occur. TAVI using coronary alignment, rather than commissural alignment, may further improve coronary access. To compare rates of CCO after TAVI using commissural versus coronary alignment methodology. Cardiac CT scans from 102 patients with severe (tricuspid) aortic stenosis referred for TAVI were analysed. Native cusp asymmetry and coronary eccentricity were defined and used to simulate TAVI using commissural versus coronary alignment. Rates of optimal coronary alignment (< 10° from cusp centre) and severe misalignment (< 15° from coronary-commissural overlap) were compared. Additionally, the impact of valve misalignment during implantation was assessed. The native right coronary artery (RCA) origin was 15.8° (9.5 to 24°) closer to the right coronary cusp/non-coronary cusp (RCC-NCC) commissure than the centre of the right coronary cusp. The native left coronary artery (LCA) origin was 4.5° (0 to 11.5°) closer to the left coronary cusp/non-coronary cusp (LCC-NCC) commissure than the centre of the left coronary cusp (p < 0.01). Compared to commissural alignment, coronary alignment doubled the proportion of optimally-aligned RCAs (62/102 [60.8%] vs. 31/102 [30.4%]; p < 0.001), without a significant change in optimal LCA alignment (62/102 [60.8% vs. 74/102 [72.6%]; p = 0.07). There were no cases of severe misalignment with either strategy. Simulating 15° of valve misalignment resulted in severe RCA compromise risk in 7/102 (6.9%) of commissural alignment cases, compared to none using coronary alignment. Fluoroscopic projection was similar with both approaches. Coronary alignment resulted in a 2-fold increase of optimal TAVI positioning relative to the RCA ostium when compared to commissural alignment without impacting the LCA. Use of coronary alignment rather than commissural alignment may improve coronary access after TAVI and is less sensitive to valve rotational error, particularly for the right coronary artery.

Transcatheter Aortic Valve Implantation in Patients With Right Bundle-Branch Block: Should Prophylactic Pacing Be Undertaken?

INTRODUCTION: Right bundle-branch block (RBBB) is a strong predictor of the development of high-grade AV block (AVB) after TAVI. AIMS: To assess mortality, length-of-hospital stay, and cost in patients with RBBB undergoing TAVI according to whether or not they had preprocedural permanent pacemaker (PPM) implantation. METHODS AND RESULTS: A total of 121 patients with RBBB who underwent TAVI between 2009-2021 were included. A total of 41 patients (33.9%) received a prophylactic PPM by clinical preference and 45/80 patients (56%) received PPM after TAVI. Baseline characteristics were balanced. Mortality was similar at 5 years, with death in 17 patients (41.4%) in the prophylactic PPM group vs 27 (33.8%) in the no prophylactic PPM group (adjusted hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.69-2.33; P=.44). Median survival for the prophylactic PPM (4.2 years), post TAVI PPM (4.5 years) and no pacemaker (4.7 years) groups was similar. Sixteen deaths (35.6%) occurred in those receiving PPM after TAVI and 11 deaths (31.4%) occurred in those not receiving PPM (HR, 0.95; 95% CI, 0.43-2.09; P=.90). Thirty-day all-cause mortality was similar. Compared with post-TAVI PPM, prophylactic PPM reduced hospital length of stay (4.3 ± 4.5 days vs 2.5 ± 1.6 days, respectively; P=.02). For the highest and lowest complication and comorbidity scores, prophylactic PPM resulted in cost savings of £297.32 (-2.9%) and excess cost of £423.89 (+5.6%), respectively. There were no major pacing-related complications. CONCLUSIONS: More than half of patients with RBBB undergoing TAVI require PPM shortly after their valve implant. A prophylactic pacing strategy is safe, reduces length of hospital stay, and is cost effective in the United Kingdom.

Novel adaptations in percutaneous right transaxillary access for transcatheter aortic valve implantation using the sapien ultra valve.

BACKGROUND: Percutaneous transaxillary access is used as an alternative to the transfemoral approach for transcatheter aortic valve implantation in patients with severe peripheral vascular disease. The left transaxillary approach is usually preferred due to ease of valve alignment with the aortic annulus. Some patients have anatomical and physiological factors which preclude this approach. Moreover, most catheterization lab layouts make left-sided approaches to the heart awkward for imaging, visualization, procedural ease, and radiation protection. AIMS: The authors describe novel adaptations to allow successful right transaxillary access for implantation of the transcatheter heart valve using the Edwards Sapien 3 system (Edwards Lifesciences). METHODS: We searched our local structural heart database for all patients who underwent transcatheter aortic valve implantation via axillary access, from January 2021 to January 2022. Patients with left axillary access were excluded. RESULTS: We report 6 percutaneous right transaxillary cases performed in the last year using steps which allow smooth delivery of the SAPIEN 3 Ultra valve down the greater curvature of the aorta and providing co-axial alignment of the valve. Only one patient had a vascular complication with arterial dissection at the closure point managed with 8 mm x 37 mm Bentley uncovered stent at the access site. CONCLUSION: With the modifications described in our article, the right transaxillary approach has now become our preferred secondary access route for TAVI.

Valve-in-Valve Transcatheter Aortic Valve Implantation for the Failing Surgical Perceval Bioprosthesis.

INTRODUCTION: The Perceval Valve has been increasingly used in Surgical Aortic Valve Replacement (SAVR) recently due to ease of implantation. However, we have seen some cases of relatively early haemodynamic failure of the Perceval valve and these patients may then present for valve-in-valve transcatheter aortic valve implantation (ViV-TAVI). Experience of ViV-TAVI in the Perceval valve is limited. METHODS: We report our experience of VIV-TAVI in four cases of early-failing Perceval valves, two with stenosis and two with regurgitation. We also review the literature with regard to ViV-TAVI for this indication. RESULTS: Four patients aged between 66 and 78 years presented with Perceval valve dysfunction an average of 4.6 years following SAVR. All cases underwent Heart Team discussion and a ViV-TAVI procedure was planned thereafter. Strategies to ensure crossing through the centre of the valve and not outside any portion of the frame were found to be essential. Three patients had self-expanding valves implanted and one had a balloon-expandable prosthesis. The average aortic valve area (AVA) improved from 0.8 cm2 pre-procedure to 1.5 cm2 post-procedure*. The mean gradient (MG) improved from 35.5 mmHg (range 19.7-53 mmHg) pre-procedure to 14.8 mmHg (range 7-30 mmHg) post-procedure. In one patient a MG of 30 mmHg persisted following valve deployment. There were no significant peri-procedural complications. CONCLUSIONS: ViV-TAVI is a useful option for failed Perceval prostheses and appears safe and effective in this small series. Crossing inside the whole frame of the Perceval valve is essential.

Diagnostic performance of quantitative flow ratio, non-hyperaemic pressure indices and fractional flow reserve for the assessment of coronary lesions in severe aortic stenosis.

Background: Quantitative flow ratio (QFR) may be used to assess the functional significance of coronary lesions. Only limited validation exists for this technology in the setting of severe aortic stenosis. Methods: A prospective study was performed on patients who were being considered for transcatheter aortic valve implantation. QFR analysis was performed (Medis Medical Imaging System, Leiden, The Netherlands) and compared to invasive measurements of haemodynamic assessment [fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), diastolic pressure ratio during the wave-free period (dPR) and distal arterial pressure/arterial pressure (Pd/Pa)]. Results: A total of 35 patients were included in the study. Mean age was 75.5±6.5 and mean aortic valve gradient was 44.3±11.8 mmHg. There were 57 vessels analysed. The mean FFR was 0.83±0.10 and 22 vessels (39%) had a functionally significant FFR ≤0.80. QFR demonstrated a discriminatory power to predict functionally significant FFR [area under the receiver operating characteristic curve (AUC), 0.92; 95% confidence interval (CI): 0.84 to 1.00], representing a sensitivity of 73%, specificity of 91%, positive predictive value of 84%, negative predictive value of 84% and an accuracy of 84%. QFR also demonstrated a discriminatory power to predict functionally significant iFR ≤0.89 (AUC =0.92; 95% CI: 0.85 to 0.99), dPR ≤0.89 (AUC =0.90; 95% CI: 0.83 to 0.98) and Pd/Pa ≤0.92 (AUC =0.89; 95% CI: 0.80 to 0.97). Conclusions: QFR demonstrates acceptable diagnostic performance in patients with severe aortic stenosis when both FFR and non-hyperaemic pressure indices are used as reference standards.

The impact of hypo-attenuated leaflet thickening on haemodynamic valve deterioration following transcatheter aortic valve replacement.

BACKGROUND: Hypo-attenuated leaflet thickening (HALT) may occur following transcatheter aortic valve replacement (TAVR), however, it remains unclear if HALT is a predictor of haemodynamic valve deterioration (HVD). AIM: To determine the impact of HALT on the occurrence of HVD. METHODS: We prospectively evaluated 186 patients for the presence of HALT at a median of 6 weeks following TAVR (Interquartile-range [IQR] 4-12 weeks). HALT depth and area were measured. HVD encompassed any of the following: mean gradient ≥20 â€‹mmHg with an increase in gradient ≥10 â€‹mmHg from baseline, Doppler velocity index reduction ≥0.1 or new moderate-to-severe valvular regurgitation. Routine echocardiograms at discharge, one month and annually, were assessed by echo-cardiologists that were blinded to the HALT status. RESULTS: LT prevalence was 17.7% (33/186). HVD was present in 8.6% (16/186) at a median follow-up of 2 years (IQR 1-3); two required valve re-intervention and five required anticoagulation. HALT was the only independent predictor of HVD on multivariate analysis (OR 33.3, 95%CI 7.4-125). Patients with HALT were more likely to develop HVD, require repeat valve intervention and have higher trans-valvular gradients at up to 3-year follow-up. Patients with HALT had a median cumulative thickness of 2.9 â€‹mm (IQR 1.9-4.7) and area of 64.2 â€‹mm2 (IQR 40.9-91.6). Thresholds for HALT in predicting HVD were a cumulative depth of 2.4 â€‹mm (Specificity 94.1%, Sensitivity 75.0%, AUC â€‹= â€‹0.87) and cumulative area of 28 â€‹mm2 (Specificity 92.2%, Sensitivity 81.3%, AUC â€‹= â€‹0.86). CONCLUSION: HALT is an independent predictor of HVD, which exhibits specific depth and area thresholds to predict HVD. CT following TAVR may determine patients at risk of HVD.

Agreement Between iFR and Other Non-Hyperaemic Pressure Ratios in Severe Aortic Stenosis.

BACKGROUND: Instantaneous wave-free ratio (iFR) can reliably assess the physiological significance of coronary artery disease (CAD). Previous studies have demonstrated its interchangeability with other non-hyperaemic pressure ratios (NHPR), but there is no data exploring whether this association is maintained in patients with severe aortic stenosis (AS). METHODS: Forty-two patients (67 lesions) with severe AS were recruited and underwent invasive pressure-wire assessment. Data were extracted to calculate iFR, resting Pd/Pa, diastolic pressure ratios (DPR and dPR), and Diastolic Hyperaemia-Free Ratio (DFR). iFR was then compared with other NHPR to determine agreement and accuracy. RESULTS: Mean aortic gradient and dimensionless index were 44.3 ± 11.6 mmHg and 0.23 ± 0.04, respectively. Of the 67 vessels, 57% were LAD, 15% LCx, 13% RCA and 12% other. There was strong positive correlation between iFR and all other NHPR, including Pd/Pa (r = 0.91, p < 0.001), DPR (r = 0.99, p < 0.001), dPR (r = 0.97, p < 0.001) and DFR (r = 0.98, p < 0.001). While Bald-Altman analysis demonstrated that Pd/Pa and DFR were numerically different from iFR, ROC analyses demonstrated iFR ≤0.89 was accurately identified by all NHPRs; Pd/Pa (AUC = 0.965, 95% CI [0.928-0.994]), DPR (AUC = 1.000, 95% CI [1.000-1.000]), dPR (AUC = 0.974, 95% CI [0.937-1.000]), DFR (AUC = 0.989, 95% CI [0.968-1.000]). CONCLUSION: In patients with severe AS, all the included NHPR in this analysis accurately predicted iFR < 0.89. These data should reassure clinicians that use of alternative NHPR to iFR is reasonable when assessing the physiological significance of CAD in patients with severe AS.

Patients with aortic stenosis exhibit early improved endothelial function following transcatheter aortic valve replacement: The eFAST study.

BACKGROUND: Patients with severe aortic stenosis (AS) exhibit systemic endothelial dysfunction, which can be associated with myocardial ischaemia in absence of obstructive coronary disease. Transcatheter aortic valve replacement (TAVR) is used to treat severe AS in patients with high or prohibitive surgical risk. However, it remains unknown whether endothelial function recovers post-TAVR. We therefore sought to assess the early and late changes in flow-mediated dilation (FMD), a measure of endothelial function, following TAVR. METHODS: Patients undergoing TAVR for severe AS had ultrasound assessment of brachial endothelial-independent and -dependent FMD. Measurements were performed pre-TAVR, at early follow-up (<48 h post-TAVR) and late follow-up (4-6 weeks post-TAVR). RESULTS: 27 patients (mean age 82.0 ± 7.0; 33.3% female) were recruited; 37.0% had diabetes mellitus and 59.3% had hypertension. Brachial artery FMD increased from 4.2 ± 1.6% (pre-TAVR) to 9.7 ± 3.5% at early follow-up (p < 0.0001). At late follow-up, improvement compared with early follow-up was sustained (8.7 ± 1.9%, p = 0.27). Resting brachial arterial flow velocities decreased significantly at late follow-up (11.24 ± 5.16 vs. 7.73 ± 2.79 cm/s, p = 0.003). Concordantly, at late follow-up, there was decrease in resting wall shear stress (WSS; 14.8 ± 7.8 vs. 10.6 ± 4.8dyne/cm2, p = 0.01), peak WSS (73.1 ± 34.1 vs. 58.8 ± 27.8dyne/cm2, p = 0.03) and cumulative WSS (3543 ± 1852 vs. 2504 ± 1089dyne·s/cm2, p = 0.002). Additionally, a favourable inverse correlation between cumulative WSS and FMD was restored at late follow-up (r = -0.21 vs. r = 0.49). CONCLUSION: Endothelial function in patients with AS improves early post-TAVR and this improvement is sustained. This likely occurs as a result of improved arterial haemodynamics, leading to lower localised WSS and release of vasoactive mediators that may also alleviate myocardial ischaemia.

Feasibility and Validity of Computed Tomography-Derived Fractional Flow Reserve in Patients With Severe Aortic Stenosis: The CAST-FFR Study.

BACKGROUND: Coronary artery disease is common in patients with severe aortic stenosis. Computed tomography-derived fractional flow reserve (CT-FFR) is a clinically used modality for assessing coronary artery disease, however, its use has not been validated in patients with severe aortic stenosis. This study assesses the safety, feasibility, and validity of CT-FFR in patients with severe aortic stenosis. METHODS: Prospectively recruited patients underwent standard-protocol invasive FFR and coronary CT angiography (CTA). CTA images were analyzed by central core laboratory (HeartFlow, Inc) for independent evaluation of CT-FFR. CT-FFR data were compared with FFR (ischemia defined as FFR ≤0.80). RESULTS: Forty-two patients (68 vessels) underwent FFR and CTA; 39 patients (92.3%) and 60 vessels (88.2%) had interpretable CTA enabling CT-FFR computation. Mean age was 76.2±6.7 years (71.8% male). No patients incurred complications relating to premedication, CTA, or FFR protocol. Mean FFR and CT-FFR were 0.83±0.10 and 0.77±0.14, respectively. CT calcium score was 1373.3±1392.9 Agatston units. On per vessel analysis, there was positive correlation between FFR and CT-FFR (Pearson correlation coefficient, R=0.64, P<0.0001). Sensitivity, specificity, positive predictive value, and negative predictive values were 73.9%, 78.4%, 68.0%, and 82.9%, respectively, with 76.7% diagnostic accuracy. The area under the receiver-operating characteristic curve for CT-FFR was 0.83 (0.72-0.93, P<0.0001), which was higher than that of CTA and quantitative coronary angiography (P=0.01 and P<0.001, respectively). Bland-Altman plot showed mean bias between FFR and CT-FFR as 0.059±0.110. On per patient analysis, the sensitivity, specificity, positive predictive, and negative predictive values were 76.5%, 77.3%, 72.2%, and 81.0% with 76.9% diagnostic accuracy. The per patient area under the receiver-operating characteristic curve analysis was 0.81 (0.67-0.95, P<0.0001). CONCLUSIONS: CT-FFR is safe and feasible in patients with severe aortic stenosis. Our data suggests that the diagnostic accuracy of CT-FFR in this cohort potentially enables its use in clinical practice and provides the foundation for future research into the use of CT-FFR for coronary evaluation pre-aortic valve replacement.

Coronary Revascularization in Patients Undergoing Aortic Valve Replacement for Severe Aortic Stenosis.

Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist, with up to two thirds of patients with AS having significant CAD. Given the challenges when both disease states are present, these patients require a tailored approach diagnostically and therapeutically. In this review the authors address the impact of AS and aortic valve replacement (AVR) on coronary hemodynamic status and discuss the assessment of CAD and the role of revascularization in patients with concomitant AS and CAD. Remodeling in AS increases the susceptibility of myocardial ischemia, which can be compounded by concomitant CAD. AVR can improve coronary hemodynamic status and reduce ischemia. Assessment of the significance of coexisting CAD can be done using noninvasive and invasive metrics. Revascularization in patients undergoing AVR can benefit certain patients in whom CAD is either prognostically or symptomatically important. Identifying this cohort of patients is challenging and as yet incomplete. Patients with dual pathology present a diagnostic and therapeutic challenge; both AS and CAD affect coronary hemodynamic status, they provoke similar symptoms, and their respective treatments can have an impact on both diseases. Decisions regarding coronary revascularization should be based on understanding this complex relationship, using appropriate coronary assessment and consensus within a multidisciplinary team.

Exploring the relationship between biomechanical stresses and coronary atherosclerosis.

The pathophysiology of coronary atherosclerosis is multifaceted. Plaque initiation and progression are governed by a complex interplay between genetic and environmental factors acting through processes such as lipid accumulation, altered haemodynamics and inflammation. There is increasing recognition that biomechanical stresses play an important role in atherogenesis, and integration of these metrics with clinical imaging has potential to significantly improve cardiovascular risk prediction. In this review, we present the calculation of coronary biomechanical stresses from first principles and computational methods, including endothelial shear stress (ESS), plaque structural stress (PSS) and axial plaque stress (APS). We discuss the current experimental and human data linking these stresses to the natural history of coronary artery disease and explore the future potential for refining treatment options and predicting future ischaemic events.

Non-hyperaemic pressure ratios to guide percutaneous coronary intervention.

The use of fractional flow reserve (FFR) in guiding revascularisation improves patient outcomes and has been well-established in clinical guidelines. Despite this, the uptake of FFR has been limited, likely attributable to the perceived increase in procedural time and use of hyperaemic agents that can cause patient discomfort. This has led to the development of instantaneous wave-free ratio (iFR), an alternative non-hyperaemic pressure ratio (NHPR). Since its inception, the use of iFR has been supported by an increasing body of evidence and is now guideline recommended. More recently, other commercially available NHPRs including diastolic hyperaemia-free ratio and resting full-cycle ratio have emerged. Studies have demonstrated that these indices, in addition to mean distal coronary artery pressure to mean aortic pressure ratio, are mathematically analogous (with specific nuances) to iFR. Additionally, there is increasing data demonstrating the equivalent diagnostic performance of alternative NHPRs in comparison with iFR and FFR. These NHPRs are now integral within most current pressure wire systems and are commonly available in the catheter laboratory. It is therefore key to understand the fundamental differences and evidence for NHPRs to guide appropriate clinical decision-making.