Doppler assessment of aortic stenosis: reading the peak velocity is superior to velocity time integral

Introduction Previous studies of the reproducibility of echocardiographic assessment of aortic stenosis have compared only a pair of observers. The aim of this study was to assess reproducibility across a large group of observers and compare the reproducibility of reading the peak versus the velocity time integral.Methods 25 observers reviewed continuous wave (CW) aortic valve and pulsed wave (PW) LVOT Doppler traces from 20 sequential cases of aortic stenosis in random order. Each operator unknowingly measured the peak velocity and velocity time integral (VTI) twice for each case, with the traces stored for analysis. We undertook a mixed-model analysis of the sources of variance for peak and VTI measurements.Results Measuring the peak is more reproducible than VTI for both PW (coefficient of variation 9.6% versus 15.9%, p<0.001) and CW traces (coefficient of variation 4.0% versus 9.6%, p<0.001), as shown in Figure 1. VTI is inferior because, compared to the middle, it is difficult to reproducibly trace the steep beginning (standard deviation 3.7x and 1.8x larger for CW and PW respectively) and end (standard deviation 2.4x and 1.5x larger for CW and PW respectively). Dimensionless index reduces the coefficient of variation (19% reduction for VTI, 11% reduction for peak) partly because it cancels correlated errors: an operator who over-measures a CW trace is likely to over-measure the matching PW trace (r=0.39, p<0.001?for VTI, r=0.41, p<0.001?for peak), as shown in Figure 2.Conclusions It is more reproducible to measure the peak of a Doppler trace than the VTI, because it is difficult to trace the steep slopes at the beginning and end reproducibly. The difference is non-trivial: an average operator would be 95% confident detecting a 11.1% change in peak velocity but a much larger 27.4% change in VTI. A clinical trial of an intervention for aortic stenosis with a VTI endpoint would need to be 2.4 times larger than one with a peak velocity endpoint. Part of the benefit of dimensionless index in improving reproducibility arises because it cancels individual operators tendency to consistently over- or under-read traces.</p

Open-source, vendor-independent, automated multi-beat tissue Doppler echocardiography analysis

Current guidelines for measuring cardiac function by tissue Doppler recommend using multiple beats, but this has a time cost for human operators. We present an open-source, vendor-independent, drag-and-drop software capable of automating the measurement process. A database of ~8000 tissue Doppler beats (48 patients) from the septal and lateral annuli were analyzed by three expert echocardiographers. We developed an intensity- and gradient-based automated algorithm to measure tissue Doppler velocities. We tested its performance against manual measurements from the expert human operators. Our algorithm showed strong agreement with expert human operators. Performance was indistinguishable from a human operator: for algorithm, mean difference and SDD from the mean of human operators’ estimates 0.48?±?1.12 cm/s (R2?=?0.82); for the humans individually this was 0.43?±?1.11 cm/s (R2?=?0.84), ?0.88?±?1.12 cm/s (R2?=?0.84) and 0.41?±?1.30 cm/s (R2?=?0.78). Agreement between operators and the automated algorithm was preserved when measuring at either the edge or middle of the trace. The algorithm was 10-fold quicker than manual measurements (p?</p

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease: Physiology-Stratified Analysis of ORBITA

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR (Pinteraction=0.318) or iFR (Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR (Pinteraction<0.00001) and decreasing iFR (Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR (Pinteraction=0.849) or iFR (Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR (Pinteraction=0.693) nor iFR (Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease: Physiology-Stratified Analysis of ORBITA

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR (Pinteraction=0.318) or iFR (Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR (Pinteraction<0.00001) and decreasing iFR (Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR (Pinteraction=0.849) or iFR (Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR (Pinteraction=0.693) nor iFR (Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI

Dobutamine stress echocardiography ischemia as a predictor of the placebo-controlled efficacy of percutaneous coronary intervention in stable coronary artery disease: the stress echo-stratified analysis of ORBITA

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina).METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling.RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426).CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI

Placebo-controlled efficacy of percutaneous coronary intervention for focal and diffuse patterns of stable coronary artery disease

Background: Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom end points. Methods: One hundred sixty-four patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment before randomization. Focal disease was defined as a ≥0.03 iFR unit drop within 15 mm, rather than over a longer distance. Analyses were performed using regression modeling. Results: In the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (mean FFR and iFR, focal 0.60±0.15 and 0.65±0.24, diffuse 0.78±0.10 and 0.88±0.08, respectively, P<0.0001). With adjustment for this difference, PCI for focal stenoses resulted in significantly greater reduction in stress echo ischemia than PCI for diffuse disease (P<0.05). The effect of PCI on between-arm pre-randomization adjusted exercise time was 9.32 seconds (95% CI, −17.1 to 35.7 seconds; P=0.487). When stratified for pattern of disease, there was no detectable difference between focal and diffuse CAD (Pinteraction=0.700). PCI improved Seattle Angina Questionnaire angina frequency score and freedom from angina more than placebo (P=0.034; P=0.0035). However, there was no evidence of interaction between the physiological pattern of CAD and these effects (Pinteraction=0.436; Pinteraction=0.908). Conclusions: PCI achieved significantly greater reduction of stress echocardiography ischemia in focal compared with diffuse CAD. However, for symptom end points, no such difference was observed

Fractional flow reserve and instantaneous wave-free ratio as predictors of the placebo-controlled response to percutaneous coronary intervention in stable coronary artery disease

Background: ORBITA-2 (the Placebo-Controlled Trial of Percutaneous Coronary Intervention for the Relief of Stable Angina) provided evidence for the role of percutaneous coronary intervention (PCI) for angina relief in stable coronary artery disease. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are often used to guide PCI; however, their ability to predict placebo-controlled angina improvement is unknown. Methods: Participants with angina, ischemia, and stable coronary artery disease were enrolled, and anti-anginal medications were stopped. Participants reported angina episodes daily for 2 weeks using the ORBITA smartphone symptom application (ORBITA-app). At the research angiogram, FFR and iFR were measured. After sedation and auditory isolation, participants were randomized to PCI or placebo before entering a 12-week blinded follow-up phase with daily angina reporting. The ability of FFR and iFR, analyzed as continuous variables, to predict the placebo-controlled effect of PCI was tested using Bayesian proportional odds modeling. Results: Invasive physiology data were available for 279 patients (140 PCI and 139 placebo). The median (interquartile range) age was 65 years (59.0–70.5), and 223 (79.9%) were male. Median FFR was 0.60 (0.46–0.73), and median iFR was 0.76 (0.50–0.86). The lower the FFR or iFR, the greater the placebo-controlled improvement with PCI across all end points. There was strong evidence that a patient with an FFR at the lower quartile would have a greater placebo-controlled improvement in angina symptom score with PCI than a patient at the upper quartile (FFR, 0.46 versus 0.73: odds ratio, 2.01; 95% credible interval, 1.79–2.26; probability of interaction, >99.9%). Similarly, there was strong evidence that a patient with an iFR at the lower quartile would have greater placebo-controlled improvement in angina symptom score with PCI than a patient with an iFR at the upper quartile (iFR, 0.50 versus 0.86: odds ratio, 2.13; 95% credible interval, 1.87–2.45; probability of interaction, >99.9%). The relationship between benefit and physiology was seen in both Rose angina and Rose nonangina. Conclusions: Physiological stenosis severity, as measured by FFR and iFR, predicts placebo-controlled angina relief from PCI. Invasive coronary physiology can be used to target PCI to those patients who are most likely to experience benefit. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03742050.</p