Dobutamine effects on systolic and diastolic left ventricular long-axis excursion and timing - significance for the interpretation of s' and e'.

BACKGROUND: Dobutamine effects on the relationships of the peak velocity of left ventricular (LV) long-axis systolic motion (s') with systolic excursion (SExc), systolic duration (SDur) and heart rate, of LV long-axis early diastolic excursion (EDExc) with SExc, and of the peak velocity of LV long-axis early diastolic motion (e') with EDExc, early diastolic duration (EDDur) and isovolumic relaxation time (IVRT') are unknown. METHODS: Two groups of adult subjects, one young and healthy (n = 10), and one with impaired LV long-axis function (n = 10), were studied, with the aim of identifying consistent findings for the two groups and for the septal and lateral walls. Dobutamine was infused at doses of 5 and 10 µg/kg/min. The relationships between tissue Doppler imaging (TDI) variables acquired before and during dobutamine infusion were analysed using mixed effect multivariate regression modelling. RESULTS: In both groups, heart rate increased and SDur decreased during dobutamine infusion, and there were independent inverse correlations of SDur with heart rate and dobutamine dose. In contrast, there was no change in EDDur during dobutamine infusion, and no consistent changes in IVRT' independent of heart rate. s' was positively correlated with SExc and inversely correlated with SDur, and there were positive correlations between EDExc and SExc and between e' and EDExc. CONCLUSION: Dobutamine increases s' due to effects on both systolic excursion and duration and it increases e' due to the associated increases in systolic and early diastolic excursion. A lack of effect on diastolic times does not support the presence of a lusitropic effect of dobutamine.

Peri-Coronary Adipose Tissue Is a Predictor of Stent Failure in Patients Undergoing Percutaneous Coronary Intervention.

PURPOSE: Coronary inflammation is postulated as a driver of atherosclerosis and dysfunctional arterial healing which may trigger stent failure. Pericoronary adipose tissue (PCAT) attenuation, detected on computer tomography coronary angiography (CTCA), is an emerging non-invasive marker of coronary inflammation. This propensity matched study assessed the utility of both lesion specific (PCATLesion) and standardized PCAT attenuation as assessed in the proximal RCA (PCATRCA) as a predictor of stent failure in patients undergoing elective percutaneous coronary intervention. This is the first study to our knowledge that assesses the association of PCAT with stent failure. METHODS: Patients undergoing CTCA assessment for coronary artery disease with subsequent stent insertion within 60 days and repeat coronary angiography for any clinical reason within 5 years were included in the study. Stent failure was defined as binary restenosis of >50 % on quantitative coronary angiography analysis or stent thrombosis. Both PCATLesion and PCATRCA was assessed utilizing semi-automated proprietary software on baseline CTCA. Patients with stent failure were propensity matched utilizing age, sex, cardiovascular risk factors and procedural characteristics. RESULTS: One hundred and fifty-one patients met inclusion criteria. Of these, 26 (17.2 %) had study-defined failure. A significant difference in PCATLesion attenuation between patients with and without failure was observed (-79.0 ± 12.6 vs. -85.9 ± 10.3HU, p = 0.035). There was no significant difference in PCATRCA attenuation between the two groups (-79.5 ± 10.1 vs -81.0 ± 12.3HU, p = 0.50). Univariate regression analysis showed PCATLesion attenuation was independently associated with stent failure (OR 1.06, 95 % CI 1.01-1.12, P = 0.035). CONCLUSIONS: Patients with stent failure exhibit significantly increased PCATLesion attenuation at baseline. These data suggest that baseline plaque inflammation may be an important driver for coronary stent failure.

Computed tomography imaging for subclinical leaflet thrombosis following surgical and transcatheter aortic valve replacement.

Subclinical leaflet thrombosis (LT) may occur following surgical and transcatheter aortic valve replacement. Computed tomography (CT) has become an established imaging modality to diagnose subclinical LT following bioprosthetic aortic valve replacement. Even so, there is a limited (but growing) experience in utilizing CT imaging for this indication. This review emphasizes a systematic approach to acquiring and analysing CT imaging for subclinical LT, highlighting evidence surrounding clinical sequelae of subclinical LT and anti-thrombotic implications following diagnosis.

Quantitative plaque characterisation and association with acute coronary syndrome on medium to long term follow up: insights from computed tomography coronary angiography.

Background: Computed tomography coronary angiography (CTCA) is an established imaging modality widely used for diagnosing coronary artery stenosis with expanding potential for comprehensive assessment of coronary artery disease (CAD). Lesion-based analyses of high-risk plaques (HRP) on CTCA may aid further in prognostication presenting with stable chest pain. We conduct qualitative and quantitative assessments to identify HRPs that are associated with acute coronary syndrome (ACS) on a medium to long term follow-up. Methods: Retrospective cohort study of patients who underwent CTCA for suspected CAD. Obstructive stenosis (OS) is defined as ≥50% and the presence of HRP and its constituents: positive-remodelling (PR), low-attenuation-plaque (LAP; <56 HU), very-low-attenuation-plaque (vLAP; <30 HU) and spotty-calcification (SC) were recorded. A cross-sectional quantitative analysis of HRP was performed at the site of minimum-luminal-area (MLA). The primary endpoint was fatal or non-fatal ACS on follow-up. Results: A total of 1,257 patients were included (mean age 61±14 years old and 51% male) with a median follow-up of 7.24 years (interquartile range 5.5 to 7.7 years). The occurrence of ACS was significantly higher in HRP (+) patients compared to HRP (-) patients and patients with no plaques (20.5% vs. 1.6% vs. 0.4%, log-rank test P<0.001). ACS was more frequent in HRP (+)/OS (+) patients (20.7%) compared to HRP (+)/OS (-) patients (8.6%), HRP (-)/OS (+) patients (1.8%) and HRP (-)/OS (-) patients (1.0%). OS, cross-sectional plaque area (PA) and the presence of vLAP identified those HRP lesions that were more likely to cause future ACS. Cross-sectional LAP area (<56 HU) in HRP lesions added incremental prognostic value to OS in predicting ACS (P=0.008). Conclusions: The presence of OS and the LAP area at the site of MLA identify the HRP lesions that have the greatest association with development of future ACS.

Prognostic Value of Exercise Capacity in Kidney Transplant Candidates.

Background Exercise stress testing for cardiovascular assessment in kidney transplant candidates has been shown to be a feasible alternative to pharmacologic methods. Exercise stress testing allows the additional assessment of exercise capacity, which may have prognostic value for long-term cardiovascular outcomes in pre-transplant recipients. This study aimed to evaluate the prognostic value of exercise capacity on long-term cardiovascular outcomes in kidney transplant candidates. Methods and Results We retrospectively evaluated exercise capacity in 898 consecutive kidney transplant candidates between 2013 and 2020 who underwent symptom-limited exercise stress echocardiography for pre-transplant cardiovascular assessment. Exercise capacity was measured by age- and sex-predicted metabolic equivalents (METs). The primary outcome was incident major adverse cardiovascular events, defined as cardiac death, non-fatal myocardial infarction, and stroke. Cox proportional hazard multivariable modeling was performed to define major adverse cardiovascular events predictors with transplantation treated as a time-varying covariate. A total of 429 patients (48%) achieved predicted METs. During follow-up, 93 (10%) developed major adverse cardiovascular events and 525 (58%) underwent transplantation. Achievement of predicted METs was independently associated with reduced major adverse cardiovascular events (hazard ratio [HR] 0.49; [95% CI 0.29-0.82], P=0.007), as was transplantation (HR, 0.52; [95% CI 0.30-0.91], P=0.02). Patients achieving predicted METs on pre-transplant exercise stress echocardiography had favorable outcomes that were independent (HR, 0.78; [95% CI 0.32-1.92], P=0.59) and of similar magnitude to subsequent transplantation (HR, 0.97; [95% CI 0.42-2.25], P=0.95). Conclusions Achievement of predicted METs on pre-transplant exercise stress echocardiography confers excellent prognosis independent of and of similar magnitude to subsequent kidney transplantation. Future studies should assess the benefit on exercise training in this population.

Diagnostic Performance of CT-Derived Fractional Flow Reserve in Australian Patients Referred for Invasive Coronary Angiography.

BACKGROUND: Non-invasive computed tomography (CT)-derived fractional flow reserve (FFRCT) is computed from standard coronary CT angiography (CTA) datasets and provides accurate vessel-specific ischaemia assessment of coronary artery disease (CAD). To date, the technique and its diagnostic performance has not been verified in the Australian clinical context. The aim of this study was to describe and compare the diagnostic performance of FFRCT and CTA for the detection of vessel-specific ischaemia as determined by invasive fractional flow reserve (FFR) in the Australian patient population. METHODS: One-hundred-and-nine patients (219 vessels) referred for clinically mandated invasive angiography were retrospectively assessed. Each patient underwent research mandated CTA and FFRCT within 3 months of invasive angiography and invasive FFR assessment. Independent core laboratory assessments were made to determine visual CTA stenosis, FFRCT and invasive FFR values. FFRCT values were matched with the corresponding invasive FFR measurement taken at the given wire position. Visual CTA stenosis ≥50%, FFRCT values ≤0.8 and invasive FFR values ≤0.8 were considered significant for ischaemia. RESULTS: Per vessel accuracy, sensitivity, specificity, positive predictive value and negative predictive value of FFRCT were 80.4%, 80.0%, 80.6%, 64.9% and 90.0% respectively. Corresponding values for CTA were 75.1%, 87.1%, 69.2%, 58.1% and 91.7% respectively. In receiver operating characteristic curve analysis, FFRCT demonstrated superior area under the curve (AUC) compared with CTA in both per vessel (0.87 vs 0.77, p=0.004) and per patient analysis (0.86 vs 0.74, p=0.011). Per vessel AUC of combined CTA and FFRCT was superior to CTA alone (0.89 vs 0.77, p<0.0001). CONCLUSION: In this cohort of Australian patients, the diagnostic performance of FFRCT was found to be comparable to existing international literature, with demonstrated improvement in performance compared with CTA alone for the detection of vessel-specific ischaemia.

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.

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.

Left ventricular contractile reserve as a determinant of adverse clinical outcomes: a systematic review.

An abnormal left ventricular contractile reserve is often seen in patients undergoing stress echocardiogram and may indicate the presence of obstructive coronary artery disease. The techniques and indexes used to identify abnormal left ventricular contractile response and its prognostic value in the absence of known causes has not been well studied. To describe the characteristics and clinical outcomes associated with an abnormal left ventricular contractile response, we performed a systematic review that identified 27 eligible studies. A diverse range of indices were utilised to measure left ventricular contractile reserve, most commonly Δleft ventricular ejection fraction in 11 studies. Dobutamine stress echocardiogram was the most commonly performed modality (19 studies) followed by exercise stress echocardiogram (4 studies), dipyridamole stress echocardiogram (2 studies), invasive hemodynamic measurement (1 study) and dobutamine stress magnetic resonance imaging (1 study). All but one study demonstrated a significant association between the absence of left ventricular contractile reserve and increased rate of cardiovascular events, cardiac death and all-cause mortality.

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.

Pericoronary Adipose Tissue Attenuation Is Associated with High-Risk Plaque and Subsequent Acute Coronary Syndrome in Patients with Stable Coronary Artery Disease.

BACKGROUND: High-risk plaques (HRP) detected on coronary computed tomography angiography (CTA) confer an increased risk of acute coronary syndrome (ACS). Pericoronary adipose tissue attenuation (PCAT) is a novel biomarker of coronary inflammation. This study aimed to evaluate the association of PCAT with HRP and subsequent ACS development in patients with stable coronary artery disease (CAD). METHODS: Patients with stable CAD who underwent coronary CTA from 2011 to 2016 and had available outcome data were included. We studied 41 patients with HRP propensity matched to 41 controls without HRP (60 ± 10 years, 67% males). PCAT was assessed using semi-automated software on a per-patient basis in the proximal right coronary artery (PCATRCA) and a per-lesion basis (PCATLesion) around HRP in cases and the highest-grade stenosis lesions in controls. RESULTS: PCATRCA and PCATLesion were higher in HRP patients than controls (PCATRCA: -80.7 ± 6.50 HU vs. -84.2 ± 8.09 HU, p = 0.03; PCATLesion: -79.6 ± 7.86 HU vs. -84.2 ± 10.3 HU, p = 0.04), and were also higher in men (PCATRCA: -80.5 ± 7.03 HU vs. -86.1 ± 7.08 HU, p < 0.001; PCATLesion: -79.6 ± 9.06 HU vs. -85.2 ± 7.96 HU, p = 0.02). Median time to ACS was 1.9 years, within a median follow-up of 5.3 years. PCATRCA alone was higher in HRP patients who subsequently presented with ACS (-76.8 ± 5.69 HU vs. -82.0 ± 6.32 HU, p = 0.03). In time-dependent analysis, ACS was associated with HRP and PCATRCA. CONCLUSIONS: PCAT attenuation is increased in stable CAD patients with HRP and is associated with subsequent ACS development. Further investigation is required to determine the clinical implications of these findings.

Use of carnosine in the prevention of cardiometabolic risk factors in overweight and obese individuals: study protocol for a randomised, double-blind placebo-controlled trial.

INTRODUCTION: Carnosine, an over the counter food supplement, has been shown to improve glucose metabolism as well as cardiovascular risk factors in animal and human studies through its anti-inflammatory, antioxidative, antiglycating and chelating properties. The aim of this study is to establish if carnosine supplementation improves obesity, insulin sensitivity, insulin secretion, cardiovascular risk factors including arterial stiffness and endothelial function, and other risk factors related to diabetes and cardiovascular disease in the overweight and obese population. METHODS AND ANALYSIS: Fifty participants will be recruited to be enrolled in a double-blind randomised controlled trial. Eligible participants with a body mass index (BMI) between 25 and 40 kg/m2 will be randomly assigned to the intervention or placebo group. Following a medical review and oral glucose tolerance test to check eligibility, participants will then undergo testing. At baseline, participants will have anthropometric measurements (BMI, dual X-ray absorptiometry and peripheral quantitative CT scan), measurements of glucose metabolism (oral glucose tolerance test, intravenous glucose tolerance test and euglycaemic hyperinsulinaemic clamp), cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), a muscle and fat biopsy, physical activity measurement, liver fibroscan, cognitive function and questionnaires to assess dietary habits, sleep quality, depression, and quality of life. Following baseline assessments, participants will be randomised to either 2 g carnosine or placebo for 15 weeks. In the 15th week, all assessments will be repeated. The preplanned outcome metric is the change between baseline and follow-up measures. ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia. TRIAL REGISTRATION NUMBER: NCT02686996.

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.

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.

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.

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.

A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD).

BACKGROUND: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism. RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings. CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.