D Perera

Pharmacological vasodilatation in the assessment of pressure-derived collateral flow index

Assessment of the coronary collateral circulation by intracoronary pressure measurements was first described a decade ago and has rapidly become a clinically accepted standard for quantification of collateral flow. The pressure-derived collateral flow index (CFI) expresses collateral flow in relation to normal maximum myocardial perfusion and is calculated by simultaneous measurement of aortic (Pa), central venous (Pv) and coronary wedge (Pw) pressures, where CFI u200a=u200a (Pw − Pv)/(Pa − Pv). In addition to these pressure gradients, collateral flow is determined by the resistances of collateral vessels and the myocardial microvasculature. Therefore, a flow index can only be derived from pressure measurements during conditions of maximum vasodilatation, when all resistances are minimised and held constant. Maximal and steady-state hyperaemia can be induced by administration of pharmacological agents such as adenosine or papaverine, which cause reproducible vasodilatation of resistance vessels.nnCFI is assessed during transient coronary occlusion, which often induces myocardial ischaemia. The resulting hypoxia and accumulation of metabolites minimise microvascular resistance and therefore exogenous pharmacological vasodilators are often omitted during measurement of CFI. However, the depth of ischaemia and consequent effectiveness of the endogenous hyperaemic stimulus depend on a variety of anatomical, cellular and vascular factors, including collateral supply itself. Well-collateralised myocardium becomes less ischaemic1 and this may attenuate the endogenous vasodilative stimulus during coronary occlusion. We hypothesised …

Catheter induced spasm: a trap for the unwary

A 48 year old smoker with atypical chest pain and a positive exercise test was referred for percutaneous coronary intervention to the right coronary artery (RCA). Coronary angiography had shown an unobstructed left system and three discreet critical stenoses in the RCA (middle upper and lower panels). Pre-intervention angiography was performed …

124 Validation of the BCIS-1 myocardial Jeopardy score using cardiac MRI

Introduction The recently described angiographic BCIS-1 Myocardial Jeopardy Score (BCIS JS) was designed to classify the extent of coronary artery disease (CAD). It provides a semi quantitative estimate of the amount of myocardium at risk as a result of severe coronary stenoses (0=no jeopardy; 12=maximum jeopardy). Advantages include ease of use and universal applicability including classification of left main stem disease and CABG. However anatomic tests, including the BCIS JS, do not incorporate myocardial ischaemia and scar, which are important for management and prognosis. Cardiac magnetic resonance (CMR) imaging allows reliable assessments of myocardial ischaemia and scar in a single examination and was used to examine the functional relevance of the BCIS JS. Methods 60 consecutive patients with angina and known or suspected CAD referred for diagnostic x-ray coronary angiography underwent CMR examination at a single UK centre. CMR included standard functional and scar imaging and also high-resolution k-t accelerated adenosine stress and rest perfusion imaging at 1.5T (40 patients) or 3T (20 patients). Expert observers blinded to the clinical data analysed the angiographic and CMR data. The BCIS JS was calculated from visual analysis of the coronary angiogram. CMR perfusion and scar data were segmented according to the standard 17-segment model excluding the apex. Segments were subdivided into equal endo- and epicardial sub-segments, each assigned 3% of the total myocardial volume and classified as normal, ischaemia or scar. Myocardial ischaemia and scar burden were calculated and correlated with the BCIS JS individually and as a combined score (Abstract 124 figure 1).Abstract 124 Figure 1 Results Patient characteristics are summarised in the Abstract 124 table 1. 2 patients were excluded (1 claustrophobia; 1 incomplete imaging data). Mean interval ± SD between CMR and coronary angiography was 40±47u2005days. 13 patients (22%) with no history of myocardial infarction had CMR evidence of prior infarction. There was a strong correlation between the BCIS JS and myocardial ischaemic burden: Pearsons r=0.75, p<0.00001 (Abstract 124 figure 2). The BCIS JS was also correlated with the combined burden of scar and ischaemia: r = 0.77, p<0.00001. There was no difference between 3T and 1.5T CMR imaging. Area under the receiver-operating characteristic curve for BCIS JS to detect ≥10% myocardial ischaemic burden was 0.87 (95% CI 0.77 to 0.97). BCIS JS ≥6 predicted ≥10% myocardial ischaemic burden with sensitivity 68% and specificity 90%.Abstract 124 Figure 2 Correlation between myocardial ischemic burden and BCIS JS. Conclusions The BCIS JS correlated well with ischaemic burden on CMR. A BCIS JS ≥6 predicts the prognostically important ischaemic threshold of 10% with high specificity. As expected, the correlation is imperfect which is likely to be a result of difficulty predicting haemodynamic effects of angiographically moderate disease, microvascular disease and limitations of CMR imaging.Abstract 124 Table 1 Characteristic Number of patients Age (mean±SD) 65±10 Left ventricular ejection fraction (mean±standard deviation) 59±14% Male 48 (83%) Diabetes 17 (29%) Previous CABG 13 (22%) Previous percutaneous coronary intervention 22 (38%) Previous MI 10 (17%) Hypertension 38 (66%)

6 Unravelling the mechanisms of mental stress vs exercise induced myocardial ischaemia

Background Mental stress (MS) triggers myocardial ischaemia at cardiac workloads that are lower than those that cause exercise-induced ischaemia in the same patient. Methods Intracoronary pressure and flow velocity data were acquired from 15 CAD (FFR <0.8 and/or >70% stenosis) patients and 11 controls during MS (mental arithmetic, stroop test). 7 CAD patients and 5 controls also underwent cycle ergometer exercise stress (ES). Coronary flow average peak velocity (APV), microvascular resistance (MR) and Buckberg index (BI) were calculated. Results At peak MS rate pressure product (RPP), a marker of myocardial oxygen demand, increased by 4418 ± 2353mmHg.bpm (p = 0 <0001). Despite this there was no increase in coronary flow but instead a paradoxical rise in MR (p = 0.01) and a fall in the BI (p < 0.001), a surrogate for subendocardial ischaemia. Interestingly wave free MR, more reflective of vascular tone and less affected by the contractile forces of the ventricle, did not increase during RPP matched ES (see Figure 1). In contrast an increase in coronary flow predominantly driven by the forward compression and backward expansion waves was observed in the control group (p = 0.001). Conclusion A paradoxical rise in MR does occur in response to MS that is not seen with ES at similar workloads. This abnormal endothelial response correlates with the extent of atherosclerosis in the vessel. Abstract 6 Figure 1 Coronary flow and microvascular resistance in response to mental and exercise stress

9 The mechanics of cardiac contraction and coronary flow: exercise, ischaemia and anti-anginals

Background Complex cardiac-coronary interaction has been debated. We developed novel technology (A) and software (B) to analyse real-time simultaneous LV and coronary haemodynamics with delineation of the interdependence during rest, exercise, ischaemia and ISDN in coronary artery disease (CAD). Methods 25 patients. Coronary measurements (pressure-flow wire) were electronically routed into intracardiac analyser with LV haemodynamics (pressure-volume (PV) loop catheter in LV apex) were measured (rest; exercise ±significant CAD; ISDN) (A). Results Backward and forward waves in coronary circulation described relative to cardiac mechanics (C). Exercise significantly increased contractility, cardiac work, coronary flow and improved diastolic function (EDPVRB 5.7 ± 0.4;4.8 ± 0.1;p = 0.003) despite increase EDP with leftward, upward PV loop shift (D). Ischaemia was associated with reduction in contractility and mechanical efficiency, driving a rightward and upward shift of PV loop (E). ISDN drove leftward, downward shift of PV loop (F); two-step cardiovascular response 1) significant afterload and cardiac work reduction (1.4 ± 0.4;1.1 ± 0.4J), significant improvement in mechanical efficiency 2) Reduction in preload associated with improved diastolic function (tau38 ± 4;36 ± 4ms;p < 0.01). Conclusion This is the first demonstration of cardiac-coronary interaction during exercise, ischaemia and ISDN. Abstract 9 Figure 1

133 Coronary wave intensity: a novel invasive tool for predicting myocardial viability following acute coronary syndromes

Introduction Wave intensity analysis (WIA) uses simultaneous changes in intracoronary pressure and flow to characterise energy transfer within the coronary circulation. In normal hearts, flow is predominantly driven by a microcirculatory-derived, diastolic phase, backward expansion wave (BEW) and aortic-derived, systolic phase, forward compression wave (FCW) (Abstract 133 figure 1A). Regional changes in contraction and microvascular function following acute coronary syndromes (ACS) may affect these waves, but the utility of WIA in this setting remains unknown.Abstract 133 Figure 1 (A) Typical Coronary Wave Intensity Profile. (B) Quantitative LGE Mass and Regional Wall Motion Assessment

099 Dynamic three-dimensional whole heart magnetic resonance myocardial perfusion imaging: validation against the Duke Jeopardy Score to assess myocardium at risk

Background Three-dimensional (3D) myocardial perfusion cardiovascular magnetic resonance (CMR) permits whole heart coverage and can establish an estimation of myocardium at risk and ischaemic burden. For invasive estimation of ischaemic burden, semi-quantitative angiographic scores including the Duke Jeopardy Score have clinical legitimacy as the magnitude of myocardium at risk due to severe coronary stenosis is associated with an adverse prognosis. The Duke Jeopardy score combines assessment of stenosis severity and location. Objectives To determine the association between myocardium at risk defined by the Duke Jeopardy Score and 3D CMR perfusion imaging. Methods 53 patients referred for angiography underwent rest and adenosine stress 3D myocardial perfusion CMR at 3Tesla (3D turbo gradient echo, flip angle 15, TR 2.0u2005ms/TE 1.0u2005ms, 12 slices of 5u2005mm thickness, in-plane resolution 2.3×2.3u2005mm2, 10-fold k-space and time k-t broad linear speed up technique acceleration with k-t principal component analysis). Volume of myocardial hypoperfusion was calculated by a blinded observer using with GTVolume software (GyroTools, Switzerland) with quantitative methods based upon adjusting the signal intensity threshold >2 SDs below the signal of remote myocardium. Volume of hypoperfusion was calculated by summation of the contiguous slices. Jeopardy score was calculated from the coronary angiograms to quantify the myocardium at risk. The coronary tree was divided into six segments of nearly equal myocardial perfusion (eg, left anterior descending artery, major diagonal branch, circumflex artery, major obtuse marginal branch artery, right coronary artery, and posterior descending artery). A score of 2 for each significant lesion was given. Vessels were analysed by a cardiologist blinded to CMR and clinical details and assigned a score ranging from 0 (no Jeopardy) to 12 (maximum Jeopardy). Results 53 patients were scanned with 159 coronary vessels anaylsed. The mean percentage volume of hypoperfusion on 3D-CMR was 9.9% (±10.9). The mean Jeopardy Score was 4.0 (±3.9). The mean percentage volume of hypoperfusion for Jeopardy scores of 0, 6, 12 were 0, 13.1% and 36.7% respectively. Pearsons correlation coefficient showed a strong correlation (r=0.82, 95% CI 0.70 to 0.89) between the Jeopardy Score and volume of hypoperfusion on CMR (p<0.0001) (Abstract 099 figure 1).Abstract 099 Figure 1 Strong correlation between invasive measures of disease severity and ischaemic burden (r=0.82). The dotted line represents the 10% threshold for which revascularisation may confer prognostic benefit over medical therapy alone. Conclusion There is a strong correlation between myocardium at risk by invasive indices and volume of inducible ischaemia by dynamic 3D CMR whole heart perfusion imaging. 3D CMR perfusion imaging offers a non-invasive alternative method of detecting ischaemic burden and myocardium at risk for the purpose of serial studies, guiding revascularisation and risk stratification.

022 Dynamic three-dimensional whole heart magnetic resonance myocardial perfusion imaging: validation against pressure wire derived fractional flow reserve for the detection of flow-limiting coronary heart disease

Background Three-dimensional (3D) myocardial perfusion cardiovascular magnetic resonance (CMR) has recently been proposed to overcome the limited spatial coverage of conventional perfusion CMR methods. The method has shown good diagnostic accuracy for the detection of coronary artery disease determined by quantitative coronary angiography. However the relationship between the severity of a coronary stenosis on quantitative coronary angiography and its functional significance is variable. Pressure wire-derived fractional flow reserve (FFR) <0.75 correlates closely with objective evidence of reversible ischaemia and it has been demonstrated that ischaemia-guided PCI confers a prognostic benefit. Objectives To determine the diagnostic accuracy of whole heart 3D myocardial perfusion CMR against invasively determined FFR. Methods 55 patients referred for angiography underwent rest and adenosine stress 3D myocardial perfusion CMR at 3Tesla (3D turbo gradient echo, flip angle 15, TR 2.0u2005ms/TE 1.0u2005ms, 12 slices of 5u2005mm thickness, in-plane resolution 2.3×2.3u2005mm2, 10-fold k-space and time k-t broad linear speed up technique acceleration with k-t principal component analysis). Perfusion was scored visually as on a coronary territory basis on a score from 0 to 3. Ischaemic burden was calculated by quantitative segmentation of the volume of hypoenhancement. The FFR was measured in vessels with >50% severity stenosis. Fractional flow reserve <0.75 was considered haemodynamically significant. Results Two patients were excluded (one due to claustrophobia, the other had poor image quality). From the remaining 53 patients and 159 coronary vessels, 64 underwent pressure wire assessment and 39 had an FFR<0.75. Sensitivity, specificity and diagnostic accuracy of CMR analysis per patient was 90%, 91% and 91%, respectively for the detection of significant coronary artery disease. By coronary territory the values were 79%, 92% and 88%. Conclusion 3D CMR stress perfusion can detect functionally significant coronary artery disease with excellent sensitivity, specificity and predictive values when compared with FFR. 3D CMR perfusion imaging may offer an alternative method of detecting ischaemia for the purpose of guiding revascularisation and risk stratification.Abstract 022 Figure 1 3D CMR perfusion of a patient with a proximal LAD lesion with positive fractional flow reserve (FFR=0.61). Note the subendocardial perfusion defect from the base towards the apex.

025 Feasibility of combined cardiovascular MRI and percutaneous coronary intervention in a hybrid laboratory

Background The relationship between anatomy and associated pathophysiology in coronary artery disease (CAD) is complex and incompletely understood yet is important for patient management. This information cannot be comprehensively provided by a single investigative modality. A hybrid x-ray and MRI (XMR) laboratory can potentially overcome this limitation. However, the feasibility of combined invasive and non-invasive studies and percutaneous coronary intervention (PCI) in an XMR laboratory is unknown. Methods 10 patients with angina scheduled for coronary angiography or PCI underwent combined procedures an XMR laboratory. 3T Cardiovascular Magnetic Resonance (CMR) exams included serial high-resolution perfusion, functional and scar imaging. Invasive procedures included diagnostic coronary angiography, PCI and fractional flow reserve (FFR) measurements pre and post PCI. Results Four females and 6 males with mean age 73 (range 51–86) were included. All procedures were completed and well tolerated without complication. Mean study duration was 117u2005min (range 36–208). The procedures and outcomes are summarised in Abstract 025 table 1. Eight patients underwent both CMR and invasive studies. Six patients had single vessel PCI. FFR and stress perfusion imaging were both performed in 14 coronary territories (4 post PCI). Management was guided by functional information in eight patients. An example case is shown in Abstract 025 figure 1. End-diastolic (B) and end-systolic (C) frames from the short axis cine demonstrate an anterior/anteroseptal wall motion abnormality. Stress perfusion imaging pre PCI demonstrated a severe perfusion defect in the LAD territory from base to apex (E–G; blue arrows) and a defect in the RCA territory (E; green arrows). There were corresponding severe lesions in the proximal LAD with an FFR of 0.45 (D) and RCA (A). Following PCI to the LAD FFR increased to 0.98 and stress perfusion was significantly improved (I–K). The RCA territory defect remained (I; green arrows) but there was also persistent hypoperfusion in the mid anterior slice (J; blue arrow) and apical lateral wall (K; blue arrow) despite the absence of scar on late gadolinium enhancement imaging (L–N).Abstract 025 Table 1 Patient number Age Sex Coronary disease CMR stress perfusion FFR pre PCI FFR post PCI Outcome 1 65 F Minor N/A N/A Medical 2 77 M LADCx NegativeNegative N/A Medical 3 71 M RCA N/A PCI RCA 4 76 F LAD Positive 0.68 PCI LAD 5 79 M LAD Positive 0.38 0.92 PCI LAD 6 79 F LADCx NegativeNegative 0.730.90 0.83 PCI LAD 7 86 F LAD Scar N/A Medical 8 61 M CxRCA PositiveNegative 0.550.29 0.95 PCI Cx 9 75 M LADCxRCA NegativeNegativeNegative 0.830.91 Medical 10 51 M LADCxRCA PositiveNegativePositive 0.450.96 0.98 PCI LAD Cx, circumflex artery; LAD, left anterior descending artery; RCA, right coronary artery.Abstract 025 Figure 1 Conclusions Combined CMR and interventional coronary procedures are feasible and well tolerated in an XMR laboratory. This set-up has exciting research and clinical applications which should improve knowledge and management of coronary artery disease.

Effect of Warm-Up Exercise Studied with Wave Intensity Analysis

The effect of warm-up on myocardial perfusion in patients with coronary artery disease (CAD) is not well understood. Coronary wave intensity reflects the effects of cardiac contraction and relaxation on coronary blood flow dynamics. It can distinguish between left ventricular (forward, FW) and microcirculatory (backward, BW) originating contributions. Our aim was to establish whether coronary wave intensity analysis can help to elucidate the underlying mechanism.