[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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 68.238.5 SECONDS, WHEN BOTH PA AND PD WERE DECREASED (PA, 10.210.5 MM HG; PD, 18.210.8 MM HG; P0.001 FOR BOTH). THE FALL IN PA CLOSELY CORRELATED WITH THE REDUCTION IN PERIPHERAL PR (PR, 12.915.7 MM HG; P0.001; R=0.9; P0.001). PA AND PD WERE CLOSELY RELATED UNDER CONDITIONS OF PEAK (R=0.75; P0.001) AND STABLE HYPEREMIA (R=0.83; P0.001). 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.
[Show abstract][Hide abstract] ABSTRACT: To determine whether the instantaneous wave-free ratio (iFR) can detect improvement in stenosis significance after percutaneous coronary intervention (PCI) and compare this with fractional flow reserve (FFR) and whole cycle Pd/Pa.
A prospective observational study was undertaken in elective patients scheduled for PCI with FFR ≤0.80. Intracoronary pressures were measured at rest and during adenosine-mediated vasodilatation, before and after PCI. iFR, Pd/Pa and FFR values were calculated using the validated fully automated algorithms.
Coronary catheter laboratories in two UK centres and one in the USA.
120 coronary stenoses in 112 patients were assessed. The mean age was 63±10 years, while 84% were male; 39% smokers; 33% with diabetes. Mean diameter stenosis was 68±16% by quantitative coronary angiography.
Pre-PCI, mean FFR was 0.66±0.14, mean iFR was 0.75±0.21 and mean Pd/Pa 0.83±0.16. PCI increased all indices significantly (FFR 0.89±0.07, p<0.001; iFR 0.94±0.05, p<0.001; Pd/Pa 0.96±0.04, p<0.001). The change in iFR after intervention (0.20±0.21) was similar to ΔFFR 0.22±0.15 (p=0.25). ΔFFR and ΔiFR were significantly larger than resting ΔPd/Pa (0.13±0.16, both p<0.001). Similar incremental changes occurred in patients with a higher prevalence of risk factors for microcirculatory disease such as diabetes and hypertension.
iFR and FFR detect the changes in coronary haemodynamics elicited by PCI. FFR and iFR have a significantly larger dynamic range than resting Pd/Pa. iFR might be used to objectively document improvement in coronary haemodynamics following PCI in a similar manner to FFR.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To determine if adenosine administration is required for the pressure-only assessment of coronary stenoses. BACKGROUND: The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorisation. In this study we use hyperaemic stenosis resistance (HSR), a combined pressure-and-flow index as an arbiter to determine when iFR and FFR disagree, which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR. METHODS: In 51 vessels intra-coronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine mediated hyperaemia. iFR (at rest and during adenosine administration, iFRa), FFR, HSR, baseline and hyperaemic microvascular resistance were calculated using automated algorithms. RESULTS: When iFR and FFR disagreed (4 cases, 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorisation; iFR, iFRa and FFR had equally good diagnostic agreement with HSR (ROC AUC 0.93 iFR vs 0.94 iFRa and 0.96 FFR, p=0.45). CONCLUSION: iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorisation, indicating that iFR can be used as an adenosine-free alternative to FFR.
Journal of the American College of Cardiology 03/2013; · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims: Adoption of fractional flow reserve (FFR) remains low (6-8%), partly because of the time, cost and potential inconvenience associated with vasodilator administration. The instantaneous wave-Free Ratio (iFR) is a pressure-only index of stenosis severity calculated without vasodilator drugs. Before outcome trials test iFR as a sole guide to revascularisation, we evaluate the merits of a hybrid iFR-FFR decision-making strategy for universal physiological assessment. Methods and results: Coronary pressure traces from 577 stenoses were analysed. iFR was calculated as the ratio between Pd and Pa in the resting diastolic wave-free window. A hybrid iFR-FFR strategy was evaluated, by allowing iFR to defer some stenoses (where negative predictive value is high) and treat others (where positive predictive value is high), with adenosine being given only to patients with iFR in between those values. For the most recent fixed FFR cut-off (0.8), an iFR of <0.86 could be used to confirm treatment (PPV of 92%), whilst an iFR value of >0.93 could be used to defer revascularisation (NPV of 91%). Limiting vasodilator drugs to cases with iFR values between 0.86 to 0.93 would obviate the need for vasodilator drugs in 57% of patients, whilst maintaining 95% agreement with an FFR-only strategy. If the 0.75-0.8 FFR grey zone is accounted for, vasodilator drugs requirement would decrease by 76%. Conclusion: A hybrid iFR-FFR decision-making strategy for revascularisation could increase adoption of physiology-guided PCI, by more than halving the need for vasodilator administration, whilst maintaining high classification agreement with an FFR-only strategy.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 12/2012; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: (2)(meta)=83.1%). Accounting for differential allocation of higher-risk patients, primary angioplasty gave 22% lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64-0.97; P=0.029). We derive a formula, called the number needed to abolish, highlighting situations in which comparative effectiveness studies are particularly vulnerable to this bias.Conclusions-In ST-segment-elevation myocardial infarction, clinicians' preference for management of a few high-risk patients can shift mortality substantially. Comparative effectiveness research in any disease is vulnerable to this, especially diseases with an immediately identifiable high-risk subgroup that clinicians prefer to allocate to 1 therapy. For this reason, preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials.
Circulation Cardiovascular Quality and Outcomes 11/2012; · 5.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims: To evaluate the classification agreement between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with angiographic intermediate coronary stenoses. Methods and results: Three hundred and twelve patients (339 stenoses) with angiographically intermediate stenoses were included in this international clinical registry. The iFR was calculated using fully automated algorithms. The receiver operating characteristic (ROC) curve was used to identify the iFR optimal cut-point corresponding to FFR 0.8. The classification agreement of coronary stenoses as significant or non-significant was established between iFR and FFR and between repeated FFR measurements for each 0.05 quantile of FFR values, from 0.2 to 1. Close agreement was observed between iFR and FFR (area under ROC curve= 86%). The optimal iFR cut-off (for an FFR of 0.80) was 0.89. After adjustment for the intrinsic variability of FFR, the classification agreement (accuracy) between iFR and FFR was 94%. Amongst the stenoses classified as non-significant by iFR (>0.89) and as significant by FFR (≤0.8), 81% had associated FFR values located within the FFR "grey-zone" (0.75-0.8) and 41% within the 0.79-0.80 FFR range. Conclusions: In a population of intermediate coronary stenoses, the classification agreement between iFR and FFR is excellent and similar to that of repeated FFR measurements in the same sample. Vasodilator-independent assessment of intermediate stenosis seems applicable and may foster adoption of coronary physiology in the catheterisation laboratory.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 08/2012; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Wave reflection is thought to be important in the augmentation of blood pressure. However, identification of distal reflections sites remains unclear. One possible explanation for this is that wave reflection is predominately determined by an amalgamation of multiple proximal small reflections rather than large discrete reflections originating from the distal peripheries. In 19 subjects (age, 35-73 years), sensor-tipped intra-arterial wires were used to measure pressure and Doppler velocity at 10-cm intervals along the aorta, starting at the aortic root. Incident and reflected waves were identified and timings and magnitudes quantified using wave intensity analysis. Mean wave speed increased along the length of the aorta (proximal, 6.8±0.9 m/s; distal, 10.7±1.5 m/s). The incident wave was tracked moving along the aorta, taking 55±4 ms to travel from the aortic root to the distal aorta. However, the timing to the refection site distance did not differ between proximal and distal aortic measurement sites (proximal aorta, 48±5 ms versus distal aorta, 42±4 ms; P=0.3). We performed a second analysis using aortic waveforms in a nonlinear model of pulse-wave propagation. This demonstrated very similar results to those observed in vivo and also an exponential attenuation in reflection magnitude. There is no single dominant refection site in or near the distal aorta. Rather, there are multiple reflection sites along the aorta, for which the contributions are attenuated with distance. We hypothesize that rereflection of reflected waves leads to wave entrapment, preventing distal waves being seen in the proximal aorta.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to develop an adenosine-independent, pressure-derived index of coronary stenosis severity.
Assessment of stenosis severity with fractional flow reserve (FFR) requires that coronary resistance is stable and minimized. This is usually achieved by administration of pharmacological agents such as adenosine. In this 2-part study, we determine whether there is a time when resistance is naturally minimized at rest and assess the diagnostic efficiency, compared with FFR, of a new pressure-derived adenosine-free index of stenosis severity over that time.
A total of 157 stenoses were assessed. In part 1 (39 stenoses), intracoronary pressure and flow velocity were measured distal to the stenosis; in part 2 (118 stenoses), intracoronary pressure alone was measured. Measurements were made at baseline and under pharmacologic vasodilation with adenosine.
Wave-intensity analysis identified a wave-free period in which intracoronary resistance at rest is similar in variability and magnitude (coefficient of variation: 0.08 ± 0.06 and 284 ± 147 mm Hg s/m) to those during FFR (coefficient of variation: 0.08 ± 0.06 and 302 ± 315 mm Hg s/m; p = NS for both). The resting distal-to-proximal pressure ratio during this period, the instantaneous wave-free ratio (iFR), correlated closely with FFR (r = 0.9, p < 0.001) with excellent diagnostic efficiency (receiver-operating characteristic area under the curve of 93%, at FFR <0.8), specificity, sensitivity, negative and positive predictive values of 91%, 85%, 85%, and 91%, respectively.
Intracoronary resistance is naturally constant and minimized during the wave-free period. The instantaneous wave-free ratio calculated over this period produces a drug-free index of stenosis severity comparable to FFR. (Vasodilator Free Measure of Fractional Flow Reserve [ADVISE]; NCT01118481).
Journal of the American College of Cardiology 12/2011; 59(15):1392-402. · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aortic stenosis causes angina despite unobstructed arteries. Measurement of conventional coronary hemodynamic parameters in patients undergoing valvular surgery has failed to explain these symptoms. With the advent of percutaneous aortic valve replacement (PAVR) and developments in coronary pulse wave analysis, it is now possible to instantaneously abolish the valvular stenosis and to measure the resulting changes in waves that direct coronary flow.
Intracoronary pressure and flow velocity were measured immediately before and after PAVR in 11 patients with unobstructed coronary arteries. Using coronary pulse wave analysis, we calculated the intracoronary diastolic suction wave (the principal accelerator of coronary blood flow). To test physiological reserve to increased myocardial demand, we measured at resting heart rate and during pacing at 90 and 120 bpm. Before PAVR, the basal myocardial suction wave intensity was 1.9±0.3×10(-5) W · m(-2) · s(-2), and this increased in magnitude with increasing severity of aortic stenosis (r=0.59, P=0.05). This wave decreased markedly with increasing heart rate (β coefficient=-0.16×10(-4) W · m(-2) · s(-2); P<0.001). After PAVR, despite a fall in basal suction wave (1.9±0.3 versus 1.1±0.1×10(-5) W · m(-2) · s(-2); P=0.02), there was an immediate improvement in coronary physiological reserve with increasing heart rate (β coefficient=0.9×10(-3) W · m(-2) · s(-2); P=0.014).
In aortic stenosis, the coronary physiological reserve is impaired. Instead of increasing when heart rate rises, the coronary diastolic suction wave decreases. Immediately after PAVR, physiological reserve returns to a normal positive pattern. This may explain how aortic stenosis can induce anginal symptoms and their prompt relief after PAVR. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01118442.
[Show abstract][Hide abstract] ABSTRACT: Adverse left ventricular (LV) remodelling after myocardial infarction (MI) frequently leads to congestive heart failure (CHF). We have previously shown that myocardial beta-adrenoceptor density (beta-ARD) is reduced soon after acute MI and correlates with LV dilatation in the short term. The aim of the present study was to determine whether myocardial beta-ARD measured early after MI was associated with progression to CHF in the long term.
We prospectively included 61 consecutive patients (mean age, 52 +/- 11 years, 10 female) in whom MI was the first manifestation of coronary artery disease. Two to 4 weeks after MI, patients underwent positron emission tomography with S-[(11)C]CGP 12177 to measure beta-ARD and (15)O-labelled water to measure myocardial blood flow and coronary flow reserve. Patients were followed-up for a median of 12.7 years (interquartile range, 6.5-13.7 years) and incidence of CHF was recorded. Eleven patients (18%) developed CHF during follow-up. They had lower beta-ARD compared with those who did not (5.35 vs. 6.49 pmol/g, P < 0.001). In patients with myocardial beta-ARD < or =5.57 pmol/g, 10-year CHF incidence rates were higher than in patients with beta-ARD >5.57 pmol/g (57% vs. 9%, P < 0.001). In a Cox regression model, only whole-heart beta-ARD [hazard ratio (HR) 0.29; 95% confidence interval (CI), 0.15-0.58, P < 0.001] and beta-ARD in remote myocardium (HR 0.32; 95% CI, 0.16-0.61, P = 0.001) were significantly associated with the incidence of CHF at follow-up.
Reduced myocardial beta-ARD early after MI is associated with the incidence of CHF on long-term follow-up.
European Heart Journal 07/2010; 31(14):1722-9. · 14.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This retrospective study of the largest single center experience (100 patients) with off-pump robotically assisted coronary
procedures in the United Kingdom (April 2002–June 2008) aimed to rationalize patient selection, describe the technique, and
determine the learning curve, technical feasibility and operative outcome of robotically assisted Atraumatic Coronary Artery
Bypass (ACAB). Selected patients underwent either a robotic Totally Endoscopic Coronary Artery Bypass (12) or robotically
assisted ACAB (88) using a standard Da Vinci robot with three arms. A fifth of all cases had percutaneous interventions as
part of a hybrid strategy. The majority of patients were overweight men. After one hundred robotic coronary procedures, this
operation is now performed as part of a routine theatre list. The mean operative and total procedure times for robotically
assisted atraumatic procedures were 157 and 238min, respectively. These measurements were significantly less in the atraumatic
than the totally endoscopic group with a 34.3 and 20.6% reduction, respectively (P<0.001; equal variance not assumed). The procedural learning curve was short and independent from internal thoracic artery
harvesting. We have proven conclusively that robotically assisted ACAB is feasible, more so than the totally endoscopic procedure
in this particular setting. Even in the absence of an ideal stabilizer device, this procedure causes minimal disruption to
the daily operating room schedule. We have also proven that body mass index is a weak predictor of the ease of robotic internal
thoracic artery harvesting and should not affect patient selection.
KeywordsRobotic-Atraumatic-Off-pump-Cardiac-Bypass and surgery
[Show abstract][Hide abstract] ABSTRACT: The augmentation index predicts cardiovascular mortality and is usually explained as a distally reflected wave adding to the forward wave generated by systole. We propose that the capacitative properties of the aorta (the arterial reservoir) also contribute significantly to the augmentation index and have calculated the contribution of the arterial reservoir, independently of wave reflection, and assessed how these contributions change with aging. In 15 subjects (aged 53 +/- 10 yr), we measured pressure and Doppler velocity simultaneously in the proximal aorta using intra-arterial wires. We calculated the components of augmentation pressure in two ways: 1) into forward and backward (reflected) components by established separation methods, and 2) using an approach that accounts for an additional reservoir component. When the reservoir was ignored, augmentation pressure (22.7 +/- 13.9 mmHg) comprised a small forward wave (peak pressure = 6.5 +/- 9.4 mmHg) and a larger backward wave (peak pressure = 16.2 +/- 7.6 mmHg). After we took account of the reservoir, the contribution to augmentation pressure of the backward wave was reduced by 64% to 5.8 +/- 4.4 mmHg (P < 0.001), forward pressure was negligible, and reservoir pressure was the largest component (peak pressure = 19.8 +/- 9.3 mmHg). With age, reservoir pressure increased progressively (9.9 mmHg/decade, r = 0.69, P < 0.001). In conclusion, the augmentation index is principally determined by aortic reservoir function and other elastic arteries and only to a minor extent by reflected waves. Reservoir function rather than wave reflection changes markedly with aging, which accounts for the age-related changes in the aortic pressure waveform.
[Show abstract][Hide abstract] ABSTRACT: We undertook a meta-analysis to determine whether changes in wave reflection substantiate the consensus explanation of why blood pressure (BP) changes with aging.
Consensus documents attribute the aging changes in BP to wave reflection moving progressively from diastole into systole. However, the extensive quantitative data on this phenomenon have never been systematically reviewed. Individual studies have been small, and limited to a narrow age range.
Using PubMed, Cochrane, and Web of Science databases, we identified 64 studies (including 13,770 subjects, age range 4 to 91 years) reporting the timing of wave reflection, defined as the time from the onset (foot) of the pressure waveform to the shoulder point (anachrotic notch).
In subjects of all ages, reflection times were well within systole. There was a small tendency for younger subjects to have later reflection, but this was only 0.7 ms per year, whereas the weighted mean reflection time was 136 ms (99% confidence interval: 130 to 141 ms) and the mean duration of systole was 328 ms (99% confidence interval: 310 to 347 ms). At this rate of change with age, arrival of wave reflection would only be construed to be in diastole at an extrapolated age of -221 years.
These findings challenge the current consensus view that a shift in timing of wave reflection significantly contributes to the changes in the BP waveform with aging. We should re-evaluate the mechanisms of BP elevation in aging.
Journal of the American College of Cardiology 11/2009; 54(22):2087-92. · 14.09 Impact Factor