Search

[Figure: see text].

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 ( P interaction =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 ( P interaction =0.116), physical limitation ( P interaction =0.461), quality of life ( P interaction =0.689), EuroQOL 5 quality-of-life score ( P interaction =0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class ( P interaction =0.693), and treadmill exercise time ( P interaction =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., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Background: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation., Methods: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2)., Results: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s -1 versus post-TAVI 3.04±1.6 mm Hg·cm·s -1 [ P =0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [ P =0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74., Conclusions: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.

Background: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in ≈20% of cases. It is unknown whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease influences discordance between FFR and iFR measurement., Methods and Results: Three-hundred and sixty intermediate coronary lesions (345 patients; mean age, 64.4±10.3 years; 76% men) with combined FFR, iFR, and iFR pressure-wire pullback were included for analysis from an international multicenter registry. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Lesions were classified into FFR+/iFR+ (n=154; 42.7%), FFR-/iFR+ (n=38; 10.6%), FFR+/iFR- (n=41; 11.4%), and FFR-/iFR- (n=127; 35.3%) groups. The physiological pattern of disease was classified according to the iFR pullback recordings as predominantly physiologically focal (n=171; 47.5%) or predominantly physiologically diffuse (n=189; 52.5%). Median FFR and iFR were 0.80 (interquartile range, 0.75-0.85) and 0.89 (interquartile range, 0.86-0.92), respectively. FFR disagreed with iFR in 22% (79 of 360). The physiological pattern of disease was the only influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR- (58.5% [24 of 41]), and predominantly physiologically diffuse was significantly associated with FFR-/iFR+ (81.6% [31 of 38]; P<0.001 for pattern of disease between FFR+/iFR- and FFR-/iFR+ groups)., Conclusions: The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance.

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 ( P interaction =0.318) or iFR ( P interaction =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 ( P interaction <0.00001) and decreasing iFR ( P interaction <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 ( P interaction =0.849) or iFR ( P interaction =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 ( P interaction =0.693) nor iFR ( P interaction =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., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Background: Small drifts in intracoronary pressure measurements (±2 mm Hg) can affect stenosis categorization using pressure indices. This has not previously been assessed for fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and whole-cycle distal pressure/proximal pressure (Pd/Pa) indices., Methods and Results: Four hundred forty-seven stenoses were assessed with FFR, iFR, and whole-cycle Pd/Pa. Cut point values for significance were predefined as ≤0.8, <0.90, and <0.93, respectively. Pressure wire drift was simulated by offsetting the distal coronary pressure trace by ±2 mm Hg. FFR, iFR, and whole-cycle Pd/Pa indices were recalculated and stenosis misclassification quantified. Median (±median absolute deviation) values for FFR, iFR, and whole-cycle Pd/Pa were 0.81 (±0.11), 0.90 (±0.07), and 0.93 (±0.06), respectively. For the cut point of FFR, iFR, and whole-cycle Pd/Pa, 34.6% (155), 50.1% (224), and 62.2% (278) of values, respectively, lay within ±0.05 U. With ±2 mm Hg pressure wire drift, 21% (94), 25% (110), and 33% (148) of the study population were misclassified with FFR, iFR, and whole-cycle Pd/Pa, respectively. Both FFR and iFR had significantly lower misclassification than whole-cycle Pd/Pa (P<0.001). There was no statistically significant difference between the diagnostic performance of FFR and iFR (P=0.125)., Conclusions: In a substantial proportion of cases, small amounts of pressure wire drift are enough to cause stenoses to change classification. Whole-cycle Pd/Pa is more vulnerable to such reclassification than FFR and iFR., (© 2016 The Authors.)

Background: Coronary flow reserve has extensive validation as a prognostic marker in coronary disease. Although pressure-only fractional flow reserve (FFR) improves outcomes compared with angiography when guiding percutaneous coronary intervention, it disagrees with coronary flow reserve classification 30% of the time. We evaluated whether baseline instantaneous wave-free ratio (iFR) could provide an improved pressure-only estimation of underlying coronary flow reserve., Methods and Results: Invasive pressure and flow velocity were measured in 216 stenoses from 186 patients with coronary disease. The diagnostic relationship between pressure-only indices (iFR and FFR) and coronary flow velocity reserve (CFVR) was compared using correlation coefficient and the area under the receiver operating characteristic curve. iFR showed a stronger correlation with underlying CFVR (iFR-CFVR, ρ=0.68 versus FFR-CFVR, ρ=0.50; P<0.001). iFR also agreed more closely with CFVR in stenosis classification (iFR area under the receiver operating characteristic curve, 0.82 versus FFR area under the receiver operating characteristic curve, 0.72; P<0.001, for a CFVR of 2). The closer relationship between iFR and CFVR was found for different CFVR cutoffs and was particularly marked in the 0.6 to 0.9 FFR range. Hyperemic FFR flow was similar to baseline iFR flow in functionally significant lesions (FFR ≤0.75; mean FFR flow, 25.8±13.7 cm/s versus mean iFR flow, 21.5±11.7 cm/s; P=0.13). FFR flow was higher than iFR flow in nonsignificant stenoses (FFR >0.75; mean FFR flow, 42.3±22.8 cm/s versus mean iFR flow, 26.1±15.5 cm/s; P<0.001)., Conclusions: When compared with FFR, iFR shows stronger correlation and better agreement with CFVR. These results provide physiological evidence that iFR could potentially be used as a functional index of disease severity, independently from its agreement with FFR., (© 2014 American Heart Association, Inc.)

Background: Lack of re-endothelialization and neointimal coverage on stent struts has been put forward as the main underlying mechanism leading to late stent thrombosis. Incomplete stent apposition (ISA) has been observed frequently in patients with very late stent thrombosis after drug eluting stent implantation, suggesting a role of ISA in the pathogenesis of this adverse event. The aim of this study was to evaluate the impact of different degrees of ISA severity on abnormal shear rate and healing response with coverage, because of its potential implications for stent optimization in clinical practice., Methods and Results: We characterized flow profile and shear distribution in different cases of ISA with increasing strut-wall detachment distance (ranging from 100 to 500 μm). Protruding strut and strut malapposed with moderate detachment (ISA detachment distance <100 μm) have minimal disturbance to blood flow as compared with floating strut that has more significant ISA distance. In vivo impact on strut coverage was assessed retrospectively using optical coherence tomography evaluation on 72 stents (48 patients) sequentially at baseline and after 6-month follow-up. Analysis of coverage revealed an important impact of baseline strut-wall ISA distance on the risk of incomplete strut coverage at follow-up. Malapposed segments with an ISA detachment <100 μm at baseline showed complete strut coverage at follow-up, whereas segments with a maximal ISA detachment distance of 100 to 300 μm and >300 μm had 6.1% and 15.7% of their struts still uncovered at follow-up, respectively (P<0.001)., Conclusions: Flow disturbances and risk of delayed strut coverage both increase with ISA detachment distance. Insights from this study are important for understanding malapposition as a quantitative, rather than binary phenomenon (present or absent) and to define the threshold of ISA detachment that might benefit from optimization during stent implantation.

Background: We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially., Methods and Results: A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both ΔPa and ΔPd were decreased (ΔPa, -10.2±10.5 mm Hg; ΔPd, -18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, -12.9±15.7 mm Hg; P<0.001; r=0.9; P<0.001). ΔPa and ΔPd were closely related under conditions of peak (r=0.75; P<0.001) and stable hyperemia (r=0.83; P<0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ≤0.80 and 5.2% with FFR threshold <0.75 when comparing Pd/Pa at peak and stable hyperemia., Conclusions: Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher.