Distal Coronary Pressure Research Articles

Impact of Side Branch Modeling on Computation of Endothelial Shear Stress in Coronary Artery Disease: Coronary Tree Reconstruction by Fusion of 3D Angiography and OCT

BackgroundComputational fluid dynamics allow virtual evaluation of coronary physiology and shear stress (SS). Most studies hitherto assumed the vessel as a single conduit without accounting for the flow through side branches. ObjectivesThis study sought to develop a new approach to reconstruct coronary geometry that also computes outgoing flow through side branches in hemodynamic and biomechanical calculations, using fusion of optical coherence tomography (OCT) and 3-dimensional (3D) angiography. MethodsTwenty-one patients enrolled in the DOCTOR (Does Optical Coherence Tomography Optimize Revascularization) fusion study underwent OCT and 3D-angiography of the target vessel (9 left anterior descending, 2 left circumflex, 10 right coronary artery). Coronary 3D reconstruction was performed by fusion of OCT and angiography, creating a true anatomical tree model (TM) including the side branches, and a traditional single-conduit model (SCM) disregarding the side branches. ResultsThe distal coronary pressure to aortic pressure (Pd/Pa) ratio was significantly higher in TMs than in SCMs (0.904 vs. 0.842; p < 0.0001). Agreement between TM and SCM in identifying patients with a Pd/Pa ratio ≤0.80 under basal flow conditions was only k = 0.417 (p = 0.019). Average SS was 4.64 Pascal lower in TMs than in SCMs (p < 0.0001), with marked differences in the point-per-point comparison, ranging from -60.71 to 7.47 Pascal. ConclusionsTrue anatomical TMs that take into account the flow through side branches are feasible for accurate hemodynamic and biomechanical calculations. Traditional SCMs underestimate Pd/Pa and are inaccurate for regional SS estimation. Implementation of TMs might improve the accuracy of SS and virtual fractional flow reserve calculations, thus improving the consistency of biomechanical studies.

104 Changes in Resting Microvascular Resistance Explain Why Resting Flow is Preserved Despite Increasing Stenosis Severity: The Results of the Largest International Combined Coronary Pressure and Flow Study

<h3>Background</h3> We sought to use combined intracoronary pressure and flow velocity measurements to elucidate of the behaviour of the human coronary circulation in response to a stenosis. <h3>Methods</h3> 567 coronary vessels underwent simultaneous intracoronary pressure and flow velocity assessments, from which coronary flow velocity, transtenotic gradient (TG) and microvascular resistance (MVR) were computed. Measurements were made during rest over the whole cardiac cycle and the diastolic wave-free period (wfp), and also during adenosine-mediated hyperaemia. Stenoses was stratified according to severity as objectively determined by fractional flow reserve (FFR). Data is mean±SEM. Linear regression analysis estimated trends and P-values. <h3>Results</h3> The key results are shown in the Figure 1. As stenosis severity increases, from reference angiographically normal vessels to those with FFR≤0.50, resting flow velocity changed little (whole cycle, 18 ± 0.5 cm/s; p = 0.40, wfp, 25 ± 0.7 cm/s, p = 0.30). In contrast, hyperaemic flow falls from 45 to 19 cm/s (P &lt; 0.01). With increasing stenosis severity, distal pressure falls such that the TG increases from 1.5 to 46 mmHg at rest (whole cycle) and 1.6 to 56 mmHg for wfp; hyperaemic TG similarly falls from 3.5 to 55 mmHg (P &lt; 0.01 for all). Resting MVR declines as stenoses increase in severity, from 6.2 to 4.2 mmHg/cm/s at rest (P &lt; 0.01), over the wfp from 4.4 to 2.0 mmHg/cm/s (p &lt; 0.01); overall hyperaemic resistance was consistent across stenoses (2.3 ± 1.1 mmHg/cm/s; P = 0.19) but with a trend to suggest paradoxical vasoconstriction in severe stenoses. <h3>Conclusions</h3> With progressive stenosis severity, distal coronary pressure falls and transtenotic gradients enlarge but resting coronary flow is preserved and maintained by a compensatory reduction of microvascular resistance. This confirms coronary auto-regulation under resting conditions in humans and explains why resting pressure gradients can detect the haemodynamic stenosis significance. Resting gradients are therefore an assessment of the natural physiological response of a given coronary bed to the presence of a stenosis. This work is also pertinent for non-invasive approaches that attempt to model physiology using anatomy since we describe all three physiological parameters across a large dataset from real-world patients. Finally, the stability of resting flow across a wide-spectrum of stenoses suggests that it should be feasible to predict the change in a resting pressure index or gradient before stenting a given stenosis.

Wave intensity analysis and assessment of myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy

Background Coronary perfusion pressure is a combination of proximal perfusion pressure and distal coronary artery pressure resulting from contraction and relaxation of the myocardium and the consequences on the microcirculation. Wave intensity analysis (WIA) defines dominant waves causing coronary filling during the cardiac cycle and allows separation of proximally and distally originating waves.Reduced myocardial perfusion has been shown to predict mortality in hypertrophic cardiomyopathy (HCM), however no study has assessed the relationship between coronary filling patterns and downstream absolute myocardial perfusion.

May Distal Coronary Pressure Measurement taken from Anastomosed Radial Artery Grafts Predict Early-Term Graft Patency?

Background: Visual estimates on angiography are inaccurate in assessing the functional significance of a coronary stenosis. Severity of stenosis in the native coronary artery is critical to both the short and long-term patency of the radial artery. Materials and Methods: A one hundred patients were selected. Radial artery is used for all patients. After all distal anastomoses are done and the systolic blood pressure reached over 100 mmHg, we have made arterial pressure measurement from the proximal side of radial artery graft. Results: All patients were followed-up. Serial postoperative coronary angiographies were performed at the first six postoperative months. There was no death in the first postoperative six months follow-up. We have detected ten radial artery graft occlusions and string sign. Five right coronary artery, four circumflex artery and one diagonal artery radial artery grafts occluded. The percentage of systolic aortic and coronary pressure measurement (C/Ao-s %) on occluded graft patients was ranged from 81 to 97. Percentage of diastolic aortic and coronary pressure measurement (C/Ao-d%) was ranged from 83 to 90. Percentage of mean aortic and coronary pressure measurement (C/Ao-m%) was ranged from 84 to 95. Conclusion: We concluded that we can predict of radial artery prognosis based on the severity degree of coronary artery stenosis. We have found ten radial artery grafts occluded. Unfortunately ten radial artery measurements are not enough for establishing a reliable cut-off value. We need more studies for creating a cut-off value determination.

Abstract 9946: Impact of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease

Background: Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) is typically used to interrogate microvascular function; however its variability limits reliability. Alternatively, the index of microcirculatory resistance (IMR) is a direct measure of the microvasculature, but has been less thoroughly studied. We investigated sex differences in CFR and IMR in patients with angina in the absence of obstructive coronary artery disease (CAD). Methods: We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive CAD. We performed CFR, IMR, fractional flow reserve (FFR), and quantitative coronary angiography (QCA) in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn: an inverse correlate to absolute flow) at rest and hyperemia. IMR was measured as distal coronary pressure at hyperemia x hyperemic Tmn. Results: All patients had minimal or no atherosclerosis by QCA (%diameter stenosis: 23.2±12.3%), and epicardial disease was milder in women (FFR: 0.88±0.04 vs. 0.87±0.04, p=0.04). IMR was similar between the sexes (20.7±9.8 vs. 19.1±8.0, p=0.45), but CFR was lower in women (3.8±1.6 vs. 4.8±1.9, p=0.004). This was primarily due to a shorter resting Tmn in women (p=0.005), while hyperemic Tmn was identical (p=0.79) (Figure). The shorter resting Tmn in women, reflecting increased resting coronary flow, accounted for the lower CFR. In multivariate analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn, but not a predictor of IMR or hyperemic Tmn. Conclusions: Despite women and men having similar microvascular function by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The impact of sex differences should be considered in interpretation of physiologic indices using resting coronary flow.

Abstract 12019: Differential Effect of Ticagrelor versus Clopidogrel on Coronary Microvascular Function in Patients With Coronary Aertery Disease

Introduction: Differential Effect of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function in Patients with Coronary Aertery Disease Background and Objectives: Ticagrelor is a new antiplatelet drug directly blocking P2Y12-adenosine diphosphate (ADP) receptors, which show a better clinical profile compared to clopidogrel in patients with acute coronary syndrome. Ticagrelor inhibits adenosine reuptake and increases coronary blood flow by a direct dilation of the microcirculation. We aimed to evaluate the effect of ticagrelor on coronary mircrovascular function in patient with coronary artery disease (CAD) in comparison with clopidogrel. Subjects and Methods: Twenty four patient with CAD were randomized to receive a single dose of ticagrelor (180 mg) or clopidogrel (300mg or on treatment state). Coronary microvascular function was invasively measured by using the index of microvascular resistance (IMR) and coronary flow reserve (CFR). The IMR was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time (hTmn). The CFR was calculated dividing the hTmn by baseline mean transit time. Results: There were no significant differences in baseline clinical and angiographic characteristics.CFR was not significantly different in both groups. (median: 4.00 [interquartile range(IQR) 2.30 to 4.92] vs 5.10 [IQR: 3.72 to 7.90], p = 0.24) However, IMR was significantly lower in ticagrelor than clopidogrel treated patients at 140 μg/kg per minute adenosine infusion rate. (median: 10.74 [interquartile range (IQR) 8.02 to 12.31] vs 15.56 [IQR: 10.77 to 29.74], p =0.05). Conclusions: In patients with CAD, ticagrelor might improves coronary microvascular functionel. These results suggest that ticagrelor could contribute to better clinical outcomes in CAD patients.

Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction.

Invasive assessment of coronary physiology (IACP) offers important prognostic insights in ST-segment elevation myocardial infarction (STEMI) but the dynamics of coronary recovery are poorly understood. This study sought to examine the evolution of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), ratio of distal coronary pressure (Pd) to mean aortic pressure (Pa), and fractional flow reserve (FFR) in patients undergoing primary percutaneous coronary intervention (PPCI). 82 patients with STEMI underwent IACP at PPCI. Repeat IACP was performed in 61 patients (74%) at day 1 and in 46 patients (56%) at 6 months. Contrast-enhanced cardiac magnetic resonance imaging (CMR) was performed in 45 patients (55%) at day 1 and in 41 patients (50%) at 6 months. Changes in IACP were compared between patients with and without microvascular obstruction (MVO) on CMR. MVO was present in 21 of 45 patients (47%). Patients with MVO had lower CFR at PPCI and day 1 (p< 0.05) and a trend toward higher IMR values (p= 0.07). At 6 months, CFR and IMR were not significantly different between thegroups. Baseline flow and Pd/Pa remained stable over time but FFR reduced significantly between PPCI and 6 months (p= 0.008); this reduction was mainly observed in patients with MVO (p= 0.006) but not in those without MVO (p=0.21). In PPCI-treated patients with STEMI, coronary microcirculation begins to recover within 24 h and recovery progresses further by 6 months. FFR significantly reduces from baseline to 6 months. The presence of MVO indicates a highly dysfunctional microcirculation.

A Unravelling the Mechanisms of Exercise Induced Ischaemia, its Optimal Assessment, and Alleviation with Nitroglycerine

IntroductionThe mechanisms governing exercise-induced angina, its alleviation by the most common anti-anginal drug, nitroglycerine (GTN), and the best techniques to elucidate whether a stenosis causes sufficient ischaemia to warrant revascularisation...

Hyperemia-free delineation of epicardial and microvascular impairments using a basal index.

The assessment of functional coronary lesion severity using intracoronary hemodynamic parameters like the pressure-derived fractional flow reserve and the flow-derived coronary flow reserve are known to rely critically on the establishment of maximal hyperemia. We evaluated a hyperemia-free index, basal pressure drop coefficient (bCDP), that combines pressure and velocity for simultaneous assessment of the status of both epicardial and microvascular circulations. In 23 pigs, simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual-sensor tipped guidewire in the settings of both normal and abnormal microcirculation with the presence of epicardial lesions of area stenosis (AS) < 50% and AS > 50%. The bCDP, a parameter based on fundamental fluid dynamics principles, was calculated as the transtenotic pressure-drop divided by the dynamic pressure in the distal vessel, measured under baseline (without hyperemia) conditions. The group mean values of bCDP for normal (84 ± 18) and abnormal (124.5 ± 15.6) microcirculation were significantly different. Similarly, the mean values of bCDP from AS < 50% (72.5 ± 16.1) and AS > 50% (136 ± 17.2) were also significantly different (p < 0.05). The bCDP could significantly distinguish between lesions of AS < 50% to AS > 50% under normal microcirculation (52.1 vs. 85.8; p < 0.05) and abnormal microcirculation (84.9 vs. 172; p < 0.05). Further, the bCDP correlated linearly and significantly with the hyperemic parameters FFR (r = 0.42, p < 0.05) and CDP (r = 0.50, p < 0.05). The bCDP is a promising clinical diagnostic parameter that can independently assess the severity of epicardial stenosis and microvascular impairment. We believe that it has an immediate appeal for detection of coronary artery disease if validated clinically.

Coronary and Microvascular Physiology During Intra-Aortic Balloon Counterpulsation

This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy. IABP is the most commonly used circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans. Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation. Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s(-1), p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s(-1), p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s(-1), p = 0.002) that was linearly related with IABP-forward compression wave energy (R(2) = 0.71, p = 0.001). Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.

Increased hyperaemic coronary microvascular resistance adds to the presence of myocardial ischaemia.

It has been argued that hyperaemic microvascular resistance (HMR), defined as the ratio of mean distal coronary pressure to flow velocity, is overestimated in the presence of a coronary stenosis compared to actual microvascular resistance (MR), due to neglecting collateral flow. We aimed to test the hypothesis that HMR allows accurate identification of microvascular functional abnormalities by evaluating the association between high or low HMR and the presence of myocardial ischaemia on non-invasive stress testing. Myocardial perfusion scintigraphy was performed in 228 patients, with 299 lesions to identify reversible myocardial ischaemia. Intracoronary distal pressure and flow velocity were assessed during adenosine-induced hyperaemia (20-40 µg, intracoronary) to determine hyperaemic stenosis resistance (HSR) and HMR. HMR >1.9 mmHg/cm/s was defined as high. The diagnostic odds ratio (OR) for myocardial ischaemia for lesions associated with high compared to low HMR was 2.6 (95% confidence interval [CI]: 1.5-4.4; p<0.001) overall, 3.3 (95% CI: 1.2-9.0; p=0.02) for lesions with HSR >0.8 mmHg/cm/s, and 1.3 (95% CI: 0.6-2.9; p=0.52) for lesions with HSR ≤0.8 mmHg/cm/s. The increased risk of myocardial ischaemia in the presence of high HMR, uncorrected for collateral flow, demonstrates that HMR is reflective of an increase in actual MR, identifying pertinent pathophysiological alterations in the microvasculature.

Myocardial bridging and sudden cardiac death: Is the actual classification exhaustive?

Myocardial bridging (MB) is a congenital coronary anomaly charac-terizedbythepresenceofabandofcardiacmuscleoverlyingasegmentof a coronary artery along its normal course in the epicardial adiposetissue [1]. The tract of the coronary artery that penetrates within themyocardium and lies beneath the muscle is called “tunnelled artery”and the presence of the MB allows dividing the vessel in three sectors:proximal, underneath and distal to the bridge [2–4]. The incidenceranges from 1.5 to 16% when assessed by angiography [4] and up to80% in some autopsy series [3,5].(SeeFig. 1.)The left anterior descending coronary (LAD) is the most frequentlyaffected vessel (70% in an autopsy series) and in some cases heartscontain more than one bridge, affecting the same vessel or differentcoronaries [1,2,4,5]. Particularly, MBs are most commonly localized inthe middle segment of the LAD [3]. MBs were also detected above acoronary vein, albeit they appear to have no clinical relevance [3].The bridge of myocardial fibers passing over the tunneled segmentcan cause narrowing of the artery during each systolic contraction.However,coronaryflowismaximalduringdiastolicphaseofthecardiaccycle and not systole. Therefore, it appeared unlikely that this systolicphenomenon could by itself result in myocardial ischemia andmyocardial bridges have long been considered as a normal anatomicalvariant without any hemodynamic or physiological relevance [6].This hypothesis was disproved by ultrasound evaluations demon-strating that during early diastole, the period of highest coronaryblood flow,theMBisresponsibleforthedelayedrelaxation,thusreduc-ing the distal coronary pressure [2,4,6]. This mechanism represents themain functional consequence of this coronary anomaly.Recently,MBshave beenclassified inbenignorpathologicalaccord-ingto the intra-myocardiallength and depth.This anomaly is thereforeconsideredpathologicalwhenthetunneledsegmentis20–30 mmlongand 2–3 mm deep [5].Pathological myocardial bridges may, in some cases, lead to is-chemia, infarction, malignant ventricular arrhythmias, and suddencardiac deaths [1,5,7,8]. Ischemic damage has been reported inshorter bridges [5], demonstrating that benign bridges can be clini-cally significant.Themechanismforischemiaiscomplexandisrelatedtothedelayedrelaxationintheearly diastole. Infact, after releasingthesystolicocclu-sion due to MB, diastolic flow increased proportionally with the dura-tion of vessel occlusion, albeit the increase in diastolic flow is not fullycompensatory. As a result, the main diastolic flow and the coronaryflow reserve are both reduced [3,6]. The likelihood of ischemia alsoincreases if MBs are located more proximally in the vessel and thetunneled segment tends to be longer and/or deeper [3].Stresses or exercises produce a rise in sympathetic drive thus facili-tating ischemia through tachycardia and increased contractility. In fact,the positive chronotropic effect leads to an increase of the systolic–diastolictimeratioandtoadecreaseofdiastolicflow,whilethepositiveinotropic effect further aggravates systolic and diastolic compression[3]. Finally, during tachycardia diastole shortens more than systole.We hereby discuss four cases of MB with heterogeneous anatomiccharacteristics and clinical presentation, summarized in Table 1.According to the actual classification based on the intra-myocardiallength and depth, the first and the second case should be consideredbenign, while the third and the fourth a pathological variant.In particular, thefirst case presented a MB over the LAD at 3 cmfrom its origin which was 18 mm long and 3 mm deep. Nonethelessthe clinical and autopticalfinding respectively of fever and divertic-ulitis could be considered the stressors capable of producing anincrease in heart rhythm. In other meanings, they represented thetrigger of sudden death in presence of a benign MB. In fact, neither

Standardized Hyperemic Stress for Fractional Flow Reserve

The article by Tarkin et al1 in this issue of Circulation: Cardiovascular Interventions adds interesting details to the extensive, well-established basis for assessing stenosis severity at maximal coronary flow induced by pharmacological vasodilation. As the authors state, all the major clinical trials of fractional flow reserve (FFR) as the basis for percutaneous coronary angioplasty were made under conditions of stable hyperemia as defined in the original protocol. Their data in this article reinforce that requirement by showing the errors in FFR if measured during initial hemodynamic changes of the systemic and coronary circulation after intravenous adenosine before stable hyperemia is reached. Article see p 654 The authors display 7 arbitrarily chosen patterns of aortic (P a ) and distal coronary pressures (P d ) all showing larger peak stenosis gradient than the steady-state hyperemic gradient. P d and the ratio P d /P a after adenosine (FFR) were related to but did not exactly parallel the stenosis gradient. Moreover, P d and FFR paralleled to some extent P a reflecting systemic hemodynamics as well as stenosis fluid dynamics, thereby raising the question of which provides the truth about stenosis severity. The answer is that stenosis gradient, P d , and FFR all tell the truth but respond to different questions. The stenosis gradient reflects the fluid dynamic characteristics of the stenosis depending on flow. P d reflects pressure that the …

Abstract 19010: Exercise but Not Pacing Affects Coronary-Cardiac Interaction via Reflected Waves From the Aorta

Background: Not only the interaction with cardiac mechanics, but also the systemic circulation determines coronary hemodynamic waveforms. Coronary wave intensity can distinguish between forward (FW) waves entering from the aorta and backward (BW) waves originating from the microcirculation. The aim of this study was to assess contributions of the systemic circulation to cardiac-coronary interaction by comparing exercise, having a profound influence on the systemic circulation, with right atrial pacing where the systemic circulation is minimally affected. Methods: During cardiac catheterization we recorded aortic pressure (Pa), distal coronary pressure (Pd) and flow velocity (U) in diseased coronary arteries. In 10 subjects heart rate (HR) was increased by right atrial pacing at 120 bpm. 11 other patients exercised using a supine cycle ergometer at increasing workload. Net wave intensity was computed as dI= (dPd/dt)(dU/dt) and the energy of the FW and BW waves was derived by the areas under the curve. Results: Resting values of systemic and coronary hemodynamic were similar in both groups, with HR = 73 ±4 bpm, Pa = 104 ±5 mmHg, Pd = 85 ±10 mmHg and U = 16.2 ±2.1 cm/s. Exercise increased HR to 108 ±7 bpm which did not differ from that during pacing. Pa and Pd increased with exercise by 20 mmHg and 8 mmHg, resp. (p&lt;0.05), whilst pacing raised Pa by only 5 mmHg (p&lt;0.05) at unchanged Pd. U similarly increased to 23.1±3.0 cm/s by pacing and exercise. Coronary wave energy at rest was the same for both groups. The BW compression wave more than doubled with both pacing and exercise, while the early FW compression wave was unchanged by exercise and much reduced by pacing from 1.9 ± 0.6 to 0.3±0.1 Jm -2 s -2 (p&lt;0.05). The FW expansion wave at the onset of relaxation increased from 1.6±0.5 to 3.5±1.0 Jm -2 s -2 (p&lt;0.05) with exercise but was not altered by pacing. The BW expansion wave that drives diastolic coronary flow more than doubled with exercise, but only increased by 63% with pacing. Conclusion: Exercise more profoundly affects cardiac-coronary interaction than pacing and improves the energy of FW and BW waves during cardiac relaxation. This is likely due to increased contractility, assisted by added reflection from the systemic circulation that enters the coronary arteries via the aorta.

Prognostic relevance of coronary collateral function: confounded or causal relationship?

Background: There is limited information on the prognostic impact of the collateral circulation in patients with coronary artery disease (CAD). Apart from the lack of data on the relation between collaterals and survival, this is due to the complete unawareness of whether such an association would be causal. Methods and results: 1'181 patients with stable CAD followed-up between March 1996 and April 2011 underwent a total of 1'771 quantitative, coronary pressure-derived collateral flow index (CFI) measurements. 152 patients had been included in randomized trials on the longitudinal effect of different arteriogenic protocols on CFI. The entire study population was prospectively included in a CFI data base containing information on collateral function parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as the ratio between mean distal coronary occlusive pressure and mean aortic pressure both subtracted by central venous pressure. Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 15-year survival rate in relation to all-cause deaths was 48% in patients with CFI<0.25, respectively 65% in the group with CFI≥0.25 (p=0.0057). Cumulative 10-year survival rate in relation to all-cause deaths was 75% in patients under no arteriogenic therapy, respectively 88% in the group with arteriogenic therapy and a significant increase in CFI at follow-up (p=0.0482; see figure). ![Figure][1] Arteriogenic therapy and survival Conclusion: A well functioning coronary collateral circulation independently predicts lowered mortality in patients with CAD. This relation appears to be causal, because improvement of collateral function by arteriogenic therapy is associated with prolonged survival. [1]: pending:yes

Functional diagnosis of coronary stenoses using pressure drop coefficient: A pilot study in humans

Myocardial fractional flow reserve (FFR) in conjunction with coronary flow reserve (CFR) is used to evaluate the hemodynamic severity of coronary lesions. However, discordant results between FFR and CFR have been observed in intermediate coronary lesions. A functional parameter, pressure drop coefficient (CDP; ratio of pressure drop to distal dynamic pressure), was assessed using intracoronary pressure drop (dp) and average peak velocity (APV). The CDP is a nondimensional ratio, derived from fundamental fluid dynamic principles. We sought to evaluate the correlation of CDP with FFR, CFR, and hyperemic stenosis resistance (HSR: ratio of pressure drop to APV) in human subjects. Twenty-seven patients with reversible perfusion defects based on SPECT were consented for the study before cardiac catheterization. Distal coronary pressure and APV were measured simultaneously for each coronary lesion using a Combowire(©) during cardiac catheterization. Reference diameter, minimal lumen diameter, and %AS were obtained by quantitative coronary angiography. Maximum hyperemia was induced by IV adenosine (140 µg/kg/min). CDP was calculated as, (Δp)/(0.5 × ρ × APV(2) ). The density of blood (ρ) was assumed to be 1.05 gm/cm(3) . The functional index, CDP, when correlated simultaneously with FFR and CFR, was found to have a significant correlation (r = 0.61; P < 0.05). Similarly a significant correlation was achieved when CDP was correlated with HSR (r = 0.91; P < 0.001). This is consistent with the definition of CDP, which is a functional parameter that includes both pressure and flow information. CDP, a nondimensional parameter combining simultaneous measurements of pressure drop and velocity data, can accurately define the severity of coronary stenoses and could prove advantageous clinically.

Prognostic relevance of coronary collateral function: confounded or causal relationship?

ObjectiveTo expand the limited information on the prognostic impact of quantitatively obtained collateral function in patients with coronary artery disease (CAD) and to estimate causality of such a relation.DesignProspective cohort...

Vasodilatory Capacity of the Coronary Microcirculation is Preserved in Selected Patients With Non–ST-Segment–Elevation Myocardial Infarction

The use of fractional flow reserve in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) is a controversial issue. We undertook a study to assess the vasodilatory capacity of the coronary microcirculation in patients with NSTEMI when compared with a model of preserved microcirculation (stable angina [SA] cohort: culprit and nonculprit vessel) and acute microcirculatory dysfunction (ST-segment-elevation myocardial infarction [STEMI] cohort). We hypothesized that the vasodilatory response of the microcirculation would be preserved in NSTEMI. A total of 140 patients undergoing single vessel percutaneous coronary intervention were included: 50 stable angina, 50 NSTEMI, and 40 STEMI. The index of microvascular resistance (IMR), fractional flow reserve, and coronary flow reserve were measured before stenting in the culprit vessel and in an angiographically normal nonculprit vessel in patients with SA. The resistive reserve ratio, a measure of the vasodilatory capacity of the microcirculation and calculated using the equation: baseline resistance index (TmnBase×PaBase[PdBase-Pw/PaBase-Pw])-IMR/IMR, where TmnBase referred to nonhyperemic transit time; PaBase and PdBase, the nonhyperemic aortic and distal coronary pressures, respectively; and Pw referred to the coronary wedge pressure, was also measured. Troponin was also measured ≤24 hours after percutaneous coronary intervention. The resistive reserve ratio was significantly lower in the STEMI patients compared with the stable angina patients both culprit and nonculprit vessel (STEMI, 1.7 versus SA culprit, 2.8; P≤0.001 and SA nonculprit, 2.9; P<0.0001) and compared with NSTEMI patients (NSTEMI, 2.46; P≤0.001). The resistive reserve ratio was similar in stable angina and NSTEMI patients (P=0.6). IMR was significantly higher pre-PCI in STEMI compared with SA and NSTEMI (IMR STEMI, 36.51 versus IMR NSTEMI, 22.73 [P=0.01] versus IMR SA, 18.26 [P<0.0001]). However, there was no significant difference in IMR pre-PCI between NSTEMI and SA (IMR NSTEMI, 22.73; IMR SA, 18.26 [P=0.1]). The vasodilatory capacity of the microcirculation is preserved in selected patients with NSTEMI. The clinical use of fractional flow reserve in the culprit vessel may be preserved in selected patents with NSTEMI.

Beneficial Effects of Intracoronary Nicorandil on Microvascular Dysfunction After Primary Percutaneous Coronary Intervention: Demonstration of Its Superiority to Nitroglycerin in a Cross-Over Study

In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 μg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

Percutaneous coronary intervention increases microvascular resistance in patients with non-ST-elevation acute coronary syndrome

In the acute coronary syndrome setting, the interaction between epicardial coronary artery stenosis and microcirculation subtended by the culprit vessel is poorly understood. The purpose of the present study was to assess the immediate impact of percutaneous coronary intervention (PCI) on microvascular resistance (MR) in patients with non-ST-elevation myocardial infarction (NSTEMI). Thirty-eight patients undergoing PCI for NSTEMI were recruited consecutively. Culprit lesions were stented over a Doppler and pressure-sensor-equipped guidewire. In the presence of epicardial stenosis, MR was calculated by taking collateral flow, as measured by the coronary wedge pressure, into consideration. After removal of epicardial stenosis, MR was calculated simply as distal coronary pressure divided by average peak velocity. When collateral flow was incorporated into the calculation, MR increased significantly from 1.70 ± 0.76 to 2.05 ± 0.72 (p=0.001) after PCI in the whole population. Periprocedural changes (Δ) in absolute values of MR and troponin T correlated significantly (r=0.629, p=0.0001). In patients who developed periprocedural myocardial infarction, MR increased significantly after PCI (1.48 ± 0.73 versus 2.28 ± 0.71, p<0.001). Nevertheless, removal of the epicardial lesion did not change MR in patients without periprocedural MI (1.91±0.73 versus 1.81±0.67, p=0.1). When collateral flow is accounted for, removal of epicardial stenosis increases MR in patients with NSTEMI undergoing PCI.