Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Fractional flow reserve use in coronary artery revascularization: A systematic review and meta-analysis.

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is recommended in revascularization guidelines for intermediate lesions. However, recent studies comparing FFR-guided PCI with non-physiology-guided revascularization have reported conflicting results. PubMed and Embase were searched for studies comparing FFR-guided PCI with non-physiology-guided revascularization strategies (angiography-guided, intracoronary imaging-guided, coronary artery bypass grafting). Data were pooled by meta-analysis using random-effects model. 26 studies enrolling 78,897 patients were included. FFR-guided PCI as compared to non-physiology-guided coronary revascularization had lower risk of all-cause mortality (odds ratio [OR] 0.79 95% confidence interval [CI] 0.64-0.99, I2 = 53%) and myocardial infarction (MI) (OR 0.74 95% CI 0.59-0.93, I2 = 44.7%). However, no differences between groups were found in terms of major adverse cardiac events (MACEs) (OR 0.86 95% CI 0.72-1.03, I2 = 72.3%) and repeat revascularization (OR 1 95% CI 0.82-1.20, I2 = 43.2%). Among patients with coronary artery disease (CAD), FFR-guided PCI as compared to non-physiology-guided revascularization was associated with a lower risk of all-cause mortality and MI.

Presence of Coronary Endothelial Dysfunction, Coronary Vasospasm, and Adenosine-Mediated Vasodilatory Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary function testing in patients with ischemia and nonobstructive coronary arteries (INOCA) commonly includes assessment of adenosine-mediated vasodilation and acetylcholine spasm provocation. The purpose of this study was to evaluate the diagnostic value of additional endothelial function testing for the diagnosis of vasomotor dysfunction in patients with INOCA. METHODS: In this retrospective cohort study, we included patients with INOCA who underwent clinically indicated comprehensive coronary function testing. Endothelial dysfunction was defined as a <50% increase in coronary blood flow, determined by Doppler flow, and/or epicardial vasoconstriction compared to baseline, in response to low-dose acetylcholine. Coronary artery spasm (CAS) was defined as vasospastic angina or microvascular angina in response to coronary high-dose acetylcholine. An impaired adenosine-mediated vasodilation was defined as a coronary flow reserve <2.5 and/or hyperemic microvascular resistance ≥2.5. RESULTS: Among all 110 patients, 79% had endothelial dysfunction, 62% had CAS, and 29% had an impaired adenosine-mediated vasodilation. Endothelial dysfunction was present in 80% of patients who tested positively for CAS and/or an impaired adenosine-mediated vasodilation. Endothelial function testing increases the diagnostic yield of coronary function testing that only incorporates adenosine testing and spasm provocation by 17% to 92%. Of patients with normal adenosine-mediated vasodilation and no inducible CAS, 68% had endothelial dysfunction. CONCLUSIONS: Concomitant endothelial dysfunction was prevalent in the vast majority of patients with INOCA with inducible CAS and/or an impaired adenosine-mediated vasodilation. In patients with INOCA without inducible CAS and normal adenosine-mediated vasodilation, two-thirds had endothelial dysfunction. These results indicate the relevance to perform endothelial function testing in patients with INOCA in view of its therapeutic implication.

Immediate impact of coronary artery bypass graft surgery on regional myocardial perfusion: Results from the Collaborative Pilot Study to Determine the Correlation Between Intraoperative Observations Using Spy Near-Infrared Imaging and Cardiac Catheterization Laboratory Physiological Assessment of Lesion Severity.

Objectives: Coronary artery bypass grafting (CABG) is performed using anatomic guidance. Data connecting the physiologic significance of the coronary vessel stenosis to the acute physiologic response to grafting are lacking. The Collaborative Pilot Study to Determine the Correlation Between Intraoperative Observations Using Spy Near-Infrared Imaging and Cardiac Catheterization Laboratory Physiological Assessment of Lesion Severity study is the first to compare preintervention coronary physiology with the acute regional myocardial perfusion change (RMP-QC) at CABG in a per-graft analysis. Methods: Non-emergent patients undergoing diagnostic catheterization suitable for multivessel CABG were enrolled. Synergy between Percutaneous Coronary Intervention with Taxus score, fractional flow reserve (FFR), instantaneous wave free ratio (iFR), and quantitative coronary angiography was documented in 75 epicardial coronary arteries, with 62 angiographically intermediate and 13 severe stenoses. At CABG, near-infrared fluorescence analysis quantified the relative change (post- vs pregrafting, termed RMP-QC) in the grafted vessel's perfusion territory. Scatter plots were constructed for RMP-QC versus quantitative coronary angiography and RMP-QC versus FFR/iFR. Exact quadrant randomization test for randomness was used. Results: There was no relationship between RMP-QC and quantitative coronary angiography percent diameter stenosis, whether all study vessels were included (P = .949) or vessels with core-lab quantitative coronary angiography only (P = .922). A significant nonrandom association between RMP-QC and FFR (P = .025), as well as between RMP-QC and iFR (P = .008), was documented. These associations remained when excluding vessels with assigned FFR and iFR values (P = .0092 and P = .0006 for FFR and iFR, respectively). Conclusions: The Collaborative Pilot Study to Determine the Correlation Between Intraoperative Observations Using Spy Near-Infrared Imaging and Cardiac Catheterization Laboratory Physiological Assessment of Lesion Severity study demonstrates there is no association between angiographic coronary stenosis severity and the acute perfusion change after grafting; there is an association between functional stenosis severity and absolute increase in regional myocardial perfusion after CABG.

Respiration-related variations in Pd/Pa ratio and fractional flow reserve in resting conditions and during intravenous adenosine administration.

AIMS: We evaluated the occurrence and physiology of respiration-related beat-to-beat variations in resting Pd/Pa and FFR during intravenous adenosine administration, and its impact on clinical decision-making. METHODS AND RESULTS: Coronary pressure tracings in rest and at plateau hyperemia were analyzed in a total of 39 stenosis from 37 patients, and respiratory rate was calculated with ECG-derived respiration (EDR) in 26 stenoses from 26 patients. Beat-to-beat variations in FFR occurred in a cyclical fashion and were strongly correlated with respiratory rate (R2  = 0.757, p < 0.001). There was no correlation between respiratory rate and variations in resting Pd/Pa. When single-beat averages were used to calculate FFR, mean ΔFFR was 0.04 ± 0.02. With averaging of FFR over three or five cardiac cycles, mean ΔFFR decreased to 0.02 ± 0.02, and 0.01 ± 0.01, respectively. Using a FFR ≤ 0.80 threshold, stenosis classification changed in 20.5% (8/39), 12.8% (5/39) and 5.1% (2/39) for single-beat, three-beat and five-beat averaged FFR. The impact of respiration was more pronounced in patients with pulmonary disease (ΔFFR 0.05 ± 0.02 vs 0.03 ± 0.02, p = 0.021). CONCLUSION: Beat-to-beat variations in FFR during plateau hyperemia related to respiration are common, of clinically relevant magnitude, and frequently lead FFR to cross treatment thresholds. A five-beat averaged FFR, overcomes clinically relevant impact of FFR variation.

Reduced Microvascular Blood Volume as a Driver of Coronary Microvascular Disease in Patients With Non-obstructive Coronary Artery Disease: Rationale and Design of the MICORDIS Study.

Background: Ischemia with non-obstructive coronary arteries (INOCA) is part of the ischemic heart disease spectrum, and is particularly observed in women. INOCA has various mechanisms, such as coronary vasospasm and coronary microvascular dysfunction (CMD). A decreased coronary flow reserve (CFR) and-or increased myocardial resistance (MR) are commonly used to diagnose CMD. However, CFR and MR do not describe all pathophysiological mechanisms underlying CMD. Increased myocardial oxygen consumption (MVO2) normally increases myocardial blood volume (MBV), independently from myocardial blood flow (MBF). In addition insulin enhances MBV in healthy skeletal muscle, and this effect is impaired in INOCA-related conditions such as diabetes and obesity. Therefore, we propose that MBV is reduced in INOCA patients. Aim: To assess whether myocardial blood volume (MBV) is decreased in INOCA patients, at baseline, during hyperinsulinemia and during stress. Design: The MICORDIS-study is a single-center observational cross-sectional cohort study (identifier NTR7515). The primary outcome is MBV, compared between INOCA patients and matched healthy controls. The patient group will undergo coronary function testing using a Doppler guidewire, intracoronary adenosine and acetylcholine to measure CFR and coronary vasospasm. Both the patient- and the control group will undergo myocardial contrast echocardiography (MCE) to determine MBV at baseline, during hyperinsulinemia and during stress. Subsequently, cardiac magnetic resonance (CMR) will be evaluated as a new and noninvasive diagnostic tool for CMD in INOCA patients. Microvascular endothelial function is a determinant of MBV and will be evaluated by non-invasive microvascular function testing using EndoPAT and by measuring NO production in circulating endothelial cells (ECFCs).

Assessing Microvascular Dysfunction in Angina With Unobstructed Coronary Arteries: JACC Review Topic of the Week.

Coronary microvascular dysfunction is a highly prevalent condition of both structural and functional coronary disorders in patients with angina and nonobstructive coronary artery disease (ANOCA). Current diagnostic modalities to assess microvascular function are related to prognosis, but these modalities have several technical shortcomings and lack the opportunity to determine true coronary blood flow and microvascular resistance. Intracoronary continuous thermodilution assessment of absolute coronary flow (Q) and microvascular resistance (R) was recently shown to be safe and feasible in ANOCA. Further exploration and implementation could lead to a better understanding and treatment of patients with ANOCA. This review discuss the coronary pathophysiology of microvascular dysfunction, provides an overview of noninvasive and invasive diagnostics, and focuses on the novel continuous thermodilution method. Finally, how these measurements of absolute Q and R could be integrated and how this would affect future clinical care are discussed.

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

BACKGROUND: Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. METHODS: We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. RESULTS: We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. CONCLUSIONS: The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.

Assessing the Haemodynamic Impact of Coronary Artery Stenoses: Intracoronary Flow Versus Pressure Measurements.

Fractional flow reserve (FFR)-guided percutaneous coronary intervention results in better long-term clinical outcomes compared with coronary angiography alone in intermediate stenoses in stable coronary artery disease (CAD). Coronary physiology measurements have emerged for clinical decision making in interventional cardiology, but the focus lies mainly on epicardial vessels rather than the impact of these stenoses on the myocardial microcirculation. The latter can be quantified by measuring the coronary flow reserve (CFR), a combined pressure and flow index with a strong ability to predict clinical outcomes in CAD. However, combined pressure-flow measurements show 30-40 % discordance despite similar diagnostic accuracy between FFR and CFR, which is explained by the effect of microvascular resistance on both indices. Both epicardial and microcirculatory involvement has been acknowledged in ischaemic heart disease, but clinical implementation remains difficult as it requires individual proficiency. The recent introduced pressure-only index instantaneous wave-free ratio, a resting adenosine-free stenosis assessment, led to a revival of interest in coronary physiology measurements. This review focuses on elaborating the coronary physiological parameters and potential of combined pressure-flow measurements in daily clinical practice.

Myocarditis in patients with subarachnoid hemorrhage: A histopathologic study.

Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis. In the myocardium of SAH patients, the amount of myeloperoxidase-positive (P < .005), CD45-positive (P < .0005), and CD68-positive (P < .0005) cells was significantly higher compared to controls. Thrombi in intramyocardial arteries were found in 22 SAH patients and 1 control. Myocytolysis was found in 6 SAH patients but not in controls. Myocarditis, consisting of an influx of neutrophil granulocytes, lymphocytes, and macrophages, coinciding with myocytolysis and thrombi in intramyocardial arteries, occurs in patients with SAH but not in controls. These findings might explain the cardiac abnormalities after SAH and may have implications for treatment.

Fractional flow reserve and minimum Pd/Pa ratio during intravenous adenosine infusion: very similar but not always the same.

AIMS: Maximum and stable hyperaemia are critical prerequisites for the accurate measurement of fractional flow reserve (FFR). However, in some patients in whom hyperaemia is induced through a central vein (IV) the minimum distal coronary pressure to aortic pressure ratio (Pd/Pa ratio) develops before the stabilisation of hyperaemia. We sought to describe the prevalence, magnitude and clinical implications of this phenomenon. METHODS AND RESULTS: The FFR tracing archive of a single institution was reviewed and a total of 104 high-quality IV-FFR recordings from 90 patients were identified. Whenever the minimum Pd/Pa ratio was found before the onset of stable hyperaemia, a search for the lowest Pd/Pa ratio within the steady-state hyperaemic plateau was performed and labelled as FFRstable. Whilst in most cases the minimum Pd/Pa ratio developed during stable hyperaemia, in 19 cases (prevalence of 18.3% [95% CI: 12.0% to 26.8%]) this value was found before the stabilisation of the hyperaemic state. In such cases, the minimum Pd/Pa ratio stabilised later at a higher level (0.77±0.09 vs. 0.81±0.08, p<0.001) (mean difference, 0.03±0.02, range, 0.01 to 0.10). In terms of dichotomous classification of stenosis severity and if FFRstable had been used to decide on revascularisation, reclassification would have occurred in three (2.9%) cases, all presenting a minimum Pd/Pa ratio ≤0.80 with FFRstable >0.80. CONCLUSIONS: During IV adenosine infusion, the minimum Pd/Pa ratio occurs before the stabilisation of hyperaemia in a significant proportion of cases. While the overall difference between the minimum Pd/Pa ratio and its FFRstable counterpart is small, reclassification of stenosis severity might occur, if choosing between the minimum and stable values of FFR within the same trace.

Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II).

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. BACKGROUND: Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. METHODS: A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. RESULTS: The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. CONCLUSIONS: The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895).

Head-to-head comparison of basal stenosis resistance index, instantaneous wave-free ratio, and fractional flow reserve: diagnostic accuracy for stenosis-specific myocardial ischaemia.

AIMS: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index. METHODS AND RESULTS: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC). Classification agreement with the reference standard was determined according to ROC curve-derived ischaemic cut-off values, as well as according to clinical cut-off values, equivalent to the 0.80 FFR cut-off. Across all stenoses, the discriminative value of BSR and FFR was equivalent (AUC: 0.90 and 0.91, respectively, p=0.46). In the iFR cohort, the discriminative value was equivalent for BSR, iFR, and FFR (AUC: 0.88, 0.84, and 0.88, respectively; p≥0.20 for all). At both ischaemic as well as clinical cut-off values, classification agreement with the reference standard was equivalent for BSR and FFR across all stenoses, as well as for BSR, iFR, and FFR in the iFR cohort. CONCLUSIONS: BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.

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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Impact of hyperaemic microvascular resistance on fractional flow reserve measurements in patients with stable coronary artery disease: insights from combined stenosis and microvascular resistance assessment.

BACKGROUND: Fractional flow reserve (FFR) aims to identify the extent of epicardial disease, but may be obscured by involvement of the coronary microvasculature. We documented the impact of hyperaemic stenosis resistance (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship with myocardial ischaemia in patients with stable coronary artery disease. METHODS AND RESULTS: We evaluated 255 coronary arteries with stenoses of intermediate severity by means of intracoronary pressure and flow measurements to determine FFR, HSR and HMR. Myocardial perfusion scintigraphy (MPS) was performed to identify inducible myocardial ischaemia. In 178 patients, HMR was additionally determined in a reference coronary artery. Target vessel HMR was stratified according to reference vessel HMR tertiles. The diagnostic OR for inducible ischaemia on MPS of a positive compared with a negative FFR was significantly higher only in the presence of a high HMR (at the 0.75 and 0.80 FFR cut-off). Among stenoses with a positive FFR, the prevalence of ischaemia was significantly higher when HMR was high despite equivalent FFR across the HMR groups. This was paralleled by a concomitant significant increase in HSR with increasing HMR across groups. The relation between FFR and HSR (r(2)=0.54, p<0.001) was modulated by the magnitude of HMR, and improved substantially after adjustment for HMR (adjusted-r(2)=0.73, p<0.001), where, for epicardial disease of equivalent severity, FFR increased with increasing HMR. CONCLUSIONS: Identification of epicardial disease severity by FFR is partly obscured by the microvascular resistance, which illustrates the necessity of combined pressure and flow measurements in daily practice.

Functional coronary stenosis severity assessed from the mean pressure gradient-velocity relationship obtained by contrast medium-induced submaximal hyperaemia.

AIMS: First, to establish the diagnostic performance of the pressure gradient at a standardised mean velocity (dPv) as derived from the cycle-averaged stenosis pressure gradient-velocity (dP-v) relationship obtained by administration of adenosine and, second, to determine whether dPv can be assessed from contrast medium-induced submaximal hyperaemia. METHODS AND RESULTS: Distal coronary pressure and velocity were simultaneously recorded in 64 patients during the response to intracoronary injection of adenosine. dPv was assessed at velocities between 20 and 50 cm/s. The pressure gradient at a mean flow velocity of 30 cm/s (dPv30) yielded an excellent diagnostic performance against FFR ≤0.8 (area under the curve 0.96; sensitivity 84%; specificity 96%; accuracy 89%). In a subgroup of 21 patients, measurements were repeated throughout contrast medium-induced reactive hyperaemia. Peak velocity and pressure gradient were lower compared to adenosine, but the course of the corresponding dP-v relationships coincided very well over the common velocity range, with no difference in dPv30. CONCLUSIONS: dPv30 reliably detects functionally significant coronary lesions. It derives from stenosis haemodynamics and can be obtained with submaximal hyperaemia, such as following injection of contrast medium, thereby obviating the maximal vasodilation by adenosine required for FFR or other established hyperaemic parameters of functional stenosis severity.

Assessment of coronary microvascular resistance in the chronic infarcted pig heart.

Pre-clinical studies aimed at treating ischemic heart disease (i.e. stem cell- and growth factor therapy) often consider restoration of the impaired microvascular circulation as an important treatment goal. However, serial in vivo measurement hereof is often lacking. The purpose of this study was to evaluate the applicability of intracoronary pressure and flow velocity as a measure of microvascular resistance in a large animal model of chronic myocardial infarction (MI). Myocardial infarction was induced in Dalland Landrace pigs (n = 13; 68.9 ± 4.1 kg) by a 75-min. balloon occlusion of the left circumflex artery (LCX). Intracoronary pressure and flow velocity parameters were measured simultaneously at rest and during adenosine-induced hyperemia, using the Combowire (Volcano) before and 4 weeks after MI. Various pressure- and/or flow-derived indices were evaluated. Hyperemic microvascular resistance (HMR) was significantly increased by 28% in the infarct-related artery, based on a significantly decreased peak average peak flow velocity (pAPV) by 20% at 4 weeks post-MI (P = 0.03). Capillary density in the infarct zone was decreased compared to the remote area (658 ± 207/mm(2) versus 1650 ± 304/mm(2) , P = 0.017). In addition, arterioles in the infarct zone showed excessive thickening of the alpha smooth muscle actin (αSMA) positive cell layer compared to the remote area (33.55 ± 4.25 µm versus 14.64 ± 1.39 µm, P = 0.002). Intracoronary measurement of HMR successfully detected increased microvascular resistance that might be caused by the loss of capillaries and arteriolar remodelling in the chronic infarcted pig heart. Thus, HMR may serve as a novel outcome measure in pre-clinical studies for serial assessment of microvascular circulation.