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.

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.

The relation of RAAS activity and endothelin-1 levels to coronary atherosclerotic burden and microvascular dysfunction in chest pain patients.

BACKGROUND AND AIMS: In this study, we investigated whether increased renin angiotensin aldosterone system (RAAS) activation and endothelin-1 levels are related to coronary artery calcium (CAC) score, total plaque volume (TPV), high risk plaque, hyperemic myocardial blood flow (MBF) and coronary microvascular dysfunction (CMD). METHODS: In a prospective, observational, cross-sectional cohort, renin as a marker for RAAS activation and endothelin-1 were measured in peripheral venous blood of 205 patients (64% men; age 58 ± 8.7 years) with suspected coronary artery disease (CAD) who underwent coronary computed tomography angiography (CCTA), [15O]H2O positron emission tomography (PET) perfusion imaging and invasive fractional flow reserve (FFR) measurements. Patients were categorized into three groups based on FFR (≤0.80) and hyperemic MBF <2.3 ml/min/g: [1] obstructive CAD (n = 92), [2] CMD (n = 26) or [3] no or non-obstructive CAD (n = 85). RESULTS: After correction for baseline characteristics, including RAAS inhibiting therapy, renin associated positively with CAC score and TPV, but not with hyperemic MBF (p < 0.01; p = 0.02 and p = 0.23). Patients with high risk plaque displayed higher levels of renin (mean logarithmic renin 1.25 ± 0.43 vs. 1.12 ± 0.35 pg/ml; p = 0.04), but not endothelin-1. Compared to no or non-obstructive CAD patients, renin was significantly elevated in obstructive CAD patients but not in CMD patients (mean logarithmic renin 1.06 ± 0.34 vs. 1.23 ± 0.36; p < 0.01 and 1.06 ± 0.34 vs. 1.16 ± 0.41 pg/ml; p = 0.65). Endothelin-1 did not differ between the three patient groups. CONCLUSIONS: Our report provides evidence that RAAS activity measured by renin concentration is elevated in patients with coronary atherosclerosis and high risk plaque but not in patients with CMD, whereas endothelin-1 is not related to either.

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

OBJECTIVES: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. METHODS: Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. RESULTS: Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm-1.sec-1 vs 4.2 ± 1.7 mmHg.cm-1.sec-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all). CONCLUSIONS: In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio.

OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to ≥70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

Interindividual Variations in the Adenosine-Induced Hemodynamics During Fractional Flow Reserve Evaluation: Implications for the Use of Quantitative Flow Ratio in Assessing Intermediate Coronary Stenoses.

Background Quantitative flow ratio (QFR), a novel functional angiography technique, computes fractional flow reserve (FFR) without pressure wires or adenosine. We investigated interindividual variations in the adenosine-induced hemodynamics during FFR assessment and their influence on QFR diagnostic performance. Methods and Results Patients with coronary stenoses who underwent intracoronary pressure and flow assessment were analyzed. Adenosine-induced hemodynamics during FFR measurement were determined by the percentage change in mean aortic pressure (%ΔPa) and the resistive reserve ratio (RRR). The diagnostic performance of QFR was evaluated and compared in each tertile of %ΔPa and RRR using FFR as reference. A total of 294 vessels (245 patients) were analyzed. Mean FFR was 0.80±0.11. Individuals showed a wide variation in the adenosine response in terms of %ΔPa (ranging from -75% to 43%; median, -9% [interquartile range, -3% to -17%]) and the RRR (ranging from 0.45 to 20.15; median, 3.1 [interquartile range, 2.1-4.9]). No significant differences for diagnostic efficiency of QFR were found between tertiles of %ΔPa (area under the curve for the receiver-operating characteristic analysis, 0.950 in tertile 1, 0.929 in tertile 2, and 0.910 in tertile 3; P=0.270) or between tertiles of the RRR (area under the curve for the receiver-operating characteristic analysis, 0.909 in tertile 1, 0.923 in tertile 2, and 0.959 in tertile 3; P=0.167). The classification agreement between QFR and FFR was not significantly modified by %ΔPa (tertile 1, 89%; tertile 2, 87%; and tertile 3, 86%; P=0.827) or by the RRR (tertile 1, 86%; tertile 2, 85%; and tertile 3, 91%; P=0.398). Conclusions Patients undergoing FFR assessment show large interindividual variations in the magnitude of adenosine-induced hemodynamics. However, such variations do not affect the diagnostic performance of QFR in assessing the functional relevance of observed stenoses.

Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction.

Importance: Percutaneous coronary intervention (PCI) of nonculprit vessels among patients with ST-segment elevation myocardial infarction (STEMI) is associated with improved clinical outcome compared with culprit vessel-only PCI. Fractional flow reserve (FFR) and coronary flow reserve are hyperemic indices used to guide revascularization. Recently, instantaneous wave-free ratio was introduced as a nonhyperemic alternative to FFR. Whether these indices can be used in the acute setting of STEMI continues to be investigated. Objective: To assess the value of hemodynamic indices in nonculprit vessels of patients with STEMI from the index event to 1-month follow-up. Design, Setting, and Participants: This substudy of the Reducing Micro Vascular Dysfunction in Revascularized STEMI Patients by Off-target Properties of Ticagrelor (REDUCE-MVI) randomized clinical trial enrolled 98 patients with STEMI who had an angiographic intermediate stenosis in at least 1 nonculprit vessel. Patient enrollment was between May 1, 2015, and September 19, 2017. After successful primary PCI, nonculprit intracoronary hemodynamic measurements were performed and repeated at 1-month follow-up. Cardiac magnetic resonance imaging was performed from 2 to 7 days and 1 month after primary PCI. Main Outcomes and Measures: The value of nonculprit instantaneous wave-free ratio, FFR, coronary flow reserve, hyperemic index of microcirculatory resistance, and resting microcirculatory resistance from the index event to 1-month follow-up. Results: Of 73 patients with STEMI included in the final analysis, 59 (80.8%) were male, with a mean (SD) age of 60.8 (9.9) years. Instantaneous wave-free ratio (SD) did not change significantly (0.93 [0.07] vs 0.94 [0.06]; P = .12) and there was no change in resting distal pressure/aortic pressure (mean [SD], 0.94 [0.06] vs 0.95 [0.06]; P = .25) from the acute moment to 1-month follow-up. The FFR decreased (mean [SD], 0.88 [0.07] vs 0.86 [0.09]; P = .001) whereas coronary flow reserve increased (mean [SD], 2.9 [1.4] vs 4.1 [2.2]; P < .001). Hyperemic index of microcirculatory resistance decreased and resting microcirculatory resistance increased from the acute moment to follow-up. The decrease in distal pressure from rest to hyperemia was smaller at the acute moment vs follow-up (mean [SD], 10.6 [11.2] mm Hg vs 14.1 [14.2] mm Hg; P = .05). This blunted acute hyperemic response correlated with final infarct size (ρ, -0.29; P = .02). The resistive reserve ratio was lower at the acute moment vs follow-up (mean [SD], 3.4 [1.7] vs 5.0 [2.7]; P < .001). Conclusions and Relevance: In the acute setting of STEMI, nonculprit coronary flow reserve was reduced and FFR was augmented, whereas instantaneous wave-free ratio was not altered. These results may be explained by an increased hyperemic microvascular resistance and a blunted adenosine responsiveness at the acute moment that was associated with infarct size.

Continuous thermodilution to assess absolute flow and microvascular resistance: validation in humans using [15O]H2O positron emission tomography.

AIMS: Continuous thermodilution is a novel technique to quantify absolute coronary flow and microvascular resistance (MVR). Notably, intracoronary infusion of saline elicits maximal hyperaemia, obviating the need for adenosine. The primary aim of this study was to validate continuous thermodilution in humans by comparing invasive measurements to [15O]H2O positron emission tomography (PET). As a secondary goal, absolute flow and MVR were compared between invasive measurements obtained with and without adenosine. METHODS AND RESULTS: Twenty-five patients underwent coronary computed tomography angiography (CCTA), [15O]H2O PET, and invasive assessment. Absolute coronary flow and MVR were measured in the left anterior descending and left circumflex artery using a dedicated infusion catheter and a temperature/pressure sensor-tipped guidewire. Invasive measurements were performed with and without adenosine. In order to compare invasive flow measurements with PET perfusion, subtending myocardial mass of the investigated vessels was derived from CCTA using the Voronoi algorithm. Invasive and non-invasive measurements of adenosine-induced hyperaemic flow and MVR showed strong correlation (r = 0.91; P < 0.001 for flow and r = 0.85; P < 0.001 for MVR) and good agreement [intraclass correlation coefficient (ICC) = 0.90; P < 0.001 for flow and ICC = 0.79; P < 0.001 for MVR]. Absolute flow and MVR also correlated well between measurements with and without adenosine (r = 0.97; P < 0.001 for flow and r = 0.98; P < 0.001 for MVR) and showed good agreement (ICC = 0.96; P < 0.001 for flow and ICC = 0.98; P < 0.001 for MVR). CONCLUSIONS: Continuous thermodilution is an accurate method to measure absolute coronary flow and MVR, which is evidenced by strong agreement with [15O]H2O PET derived flow and resistance. Absolute flow and MVR correlate highly between invasive measurements obtained with and without adenosine, which confirms that intracoronary infusion of room temperature saline elicits steady-state maximal hyperaemia.

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel.

BACKGROUND: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy. METHODS: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month. RESULTS: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.

Fractional flow reserve, instantaneous wave-free ratio, and resting Pd/Pa compared with [15O]H2O positron emission tomography myocardial perfusion imaging: a PACIFIC trial sub-study.

Aims: Guidelines recommend the use of fractional flow reserve (FFR) to guide percutaneous coronary intervention. For this purpose, physiological lesion assessment without adenosine may have a similar diagnostic accuracy as FFR. We aimed to investigate the performances of FFR, resting instantaneous wave-free ratio (iFR), and resting Pd/Pa compared with [15O]H2O positron emission tomography (PET) perfusion imaging. Methods and results: [15O]H2O PET and intracoronary pressure measurements were evaluated in 320 coronary arteries (of which 136 coronary stenoses) in 129 stable patients. The primary analysis consisting of the area-under-the-receiver-operating-characteristic curve for impaired PET hyperaemic myocardial blood flow (MBF) <2.3 mL⋅min-1⋅g-1 in coronary stenoses was 0.78 [95% confidence interval (CI): 0.70-0.85] for FFR, 0.74 (95% CI: 0.66-0.81) for iFR, and 0.75 (95% CI: 0.67-0.82) for Pd/Pa. No significant differences between area-under-the-receiver-operating-characteristic curve were observed for any two indices compared. In a secondary analysis, the diagnostic accuracy compared with impaired PET hyperaemic MBF in coronary stenoses was 72% (95% CI: 64-79%, κ: 0.44) for FFR ≤0.80, 72% (95% CI: 64-80%, κ: 0.44) for iFR ≤0.89, and 70% (95% CI: 62-78%, κ: 0.40) for Pd/Pa ≤0.92. Other secondary analyses included a comparison of physiological indices with PET hyperaemic MBF in all vessels and all of the aforementioned analyses using PET myocardial perfusion reserve as comparator. Statistical testing for the secondary analyses showed results that were consistent with the results of the primary analysis. Conclusion: Fractional flow reserve, iFR, and Pd/Pa showed a similar performance when compared with PET imaging. Our results support the validity of invasive physiological lesion assessment under resting conditions by iFR or Pd/Pa. Trial registration: Sub-study of the PACIFIC trial with clinicaltrials.gov identifier: NCT01521468.

Instantaneous wave-free ratio to guide coronary revascularisation: physiological framework, validation and differences from fractional flow reserve.

Determining the optimal treatment strategy for revascularisation of coronary artery stenosis involves the use of fractional flow reserve (FFR). To improve the low clinical uptake of physiological lesion assessment to guide revascularisation, the instantaneous wave-free period (iFR) was proposed as a simpler alternative to FFR that does not require adenosine administration. iFR is calculated as the ratio of blood pressure distal and proximal to a coronary artery stenosis during the diastolic wave-free period. The wave-free period is a part of the cardiac cycle where generation of new pressure wavefronts does not occur and resting microvascular resistance is relatively minimised. iFR indicates the haemodynamic severity of a stenosis, by assessing the extent to which the epicardial stenosis depletes the microcirculatory, autoregulatory reserve. The introduction of iFR and the potential to assess haemodynamic stenosis severity without the need for administration of potent vasodilators such as adenosine sparked an interesting debate about the fundamentals of human coronary physiology. The outcomes of two randomised clinical trials investigating iFR are pending. These studies are designed to evaluate whether iFR-guided revascularisation is non-inferior to an FFR-guided approach. The purpose of this review article is to discuss the physiological concepts underlying iFR, examine the existing validation studies and discuss the advantages and disadvantages of iFR as compared to FFR.

Reducing Microvascular Dysfunction in Revascularized Patients with ST-Elevation Myocardial Infarction by Off-Target Properties of Ticagrelor versus Prasugrel. Rationale and Design of the REDUCE-MVI Study.

Microvascular injury is present in a large proportion of patients with ST-elevation myocardial infarction (STEMI) despite successful revascularization. Ticagrelor potentially mitigates this process by exerting additional adenosine-mediated effects. This study aims to determine whether ticagrelor is associated with a better microvascular function compared to prasugrel as maintenance therapy after STEMI. A total of 110 patients presenting with STEMI and additional intermediate stenosis in another coronary artery will be studied after successful percutaneous coronary intervention (PCI) of the infarct-related artery. Patients will be randomized to treatment with ticagrelor or prasugrel for 1 year. FFR-guided PCI of the non-infarct-related artery will be performed at 1 month. Microvascular function will be assessed by measurement of the index of microcirculatory resistance (IMR) in the infarct-related artery and non-infarct-related artery, immediately after primary PCI and after 1 month. The REDUCE-MVI study will establish whether ticagrelor as a maintenance therapy may improve microvascular function in patients after revascularized STEMI.

Changes in Coronary Blood Flow After Acute Myocardial Infarction: Insights From a Patient Study and an Experimental Porcine Model.

OBJECTIVES: The aim of this study was to determine the effects of an acute myocardial infarction (AMI) on baseline and hyperemic flow in both culprit and nonculprit arteries. BACKGROUND: An impaired coronary flow reserve (CFR) after AMI is related to worse outcomes. The individual contribution of resting and hyperemic flow to the reduction of CFR is unknown. Furthermore, it is unclear whether currently used experimental models of AMI resemble the clinical situation with respect to coronary flow parameters. METHODS: Intracoronary Doppler flow velocity measurements were obtained in culprit and nonculprit arteries immediately after successfully revascularized ST-segment elevation myocardial infarction (n = 40). Stable patients without obstructive coronary artery disease served as control subjects and were selected by propensity-score matching (n = 40). Similar measurements in an AMI porcine model were taken both before and immediately after 75-min balloon occlusion of the left circumflex artery (n = 11). RESULTS: In the culprit artery, CFR was 36% lower than in matched control subjects (Δ = -0.9; 1.8 ± 0.9 vs. 2.8 ± 0.7; p < 0.001) with consistent observations in swine (Δ = -0.9; 1.5 ± 0.4 vs. 2.4 ± 0.9 for after and before AMI, respectively; p = 0.04). An increased baseline and a decreased hyperemic flow contributed to the reduction in CFR in both patients (baseline flow: Δ = +5 and hyperemic flow: Δ = -7 cm/s) and swine (baseline flow: Δ = +8 and hyperemic flow: Δ = -6 cm/s). Similar changes were observed in nonculprit arteries (CFR: 2.8 ± 0.7 vs. 2.0 ± 0.7 for STEMI patients and control subjects; p < 0.001). CFR significantly correlated with infarct size as a percentage of the left ventricle in both patients (r = -0.48; p = 0.001) and swine (r = -0.61; p = 0.047). CONCLUSIONS: CFR in both culprit and nonculprit coronary arteries decreases after AMI with contributions from both an increased baseline flow and a decreased hyperemic flow. The decreased CFR after AMI in culprit and nonculprit vessels is not a result of pre-existing microvascular dysfunction, but represents a combination of post-occlusive hyperemia, myocardial necrosis, hemorrhagic microvascular injury, compensatory hyperkinesis, and neurohumoral vasoconstriction.

Kinetics of coagulation in ST-elevation myocardial infarction following successful primary percutaneous coronary intervention.

INTRODUCTION: ST-elevated myocardial infarction (STEMI) is most frequently caused by coronary occlusion due to formation of an intracoronary thrombus in reaction to rupture of atherosclerotic plaques. Little is known about kinetics of coagulation markers after STEMI in patients treated according to current guidelines. We aimed to investigate kinetics of important coagulation markers in percutaneous coronary intervention (PCI)-treated STEMI patients. MATERIALS AND METHODS: 60 consecutive PCI-treated STEMI patients were prospectively included. Blood samples were collected immediately after as well as 1, 4 and 7 days following PCI. Samples collected 90 days after PCI served as baseline values. ADAMTS13 activity, VWF (von Willebrand factor) activity, VWF antigen, VWF propeptide, fibrinogen antigen, D-dimer, alpha2-antiplasmin (α2AP), plasmin-alpha2-antiplasmin complex (PAP), prothrombin fragment F1+2 (F1+2), prothrombin time (PT), activated partial thromboplastin time (aPTT), and anti-factor Xa (anti-Xa) were measured. Cardiac magnetic resonance (CMR) was performed at 4-6 and 90 days after PCI in 49 patients and left ventricular ejection fraction (LVEF), infarct size and microvascular injury (MVI) were determined. RESULTS: Immediately after PCI, ADAMTS13 activity, fibrinogen antigen and α2AP levels were significantly decreased and VWF activity, VWF antigen and VWF propeptide levels were significantly elevated, compared to baseline. Individual coagulation markers and different combinations thereof were not related to LVEF or infarct size at 90 days, or the occurrence of MVI at 4-6 days after PCI. CONCLUSION: Coagulation parameters show a very dynamic profile in the early days after STEMI. However, individual coagulation parameters or combinations thereof do not predict CMR-defined LVEF, infarct size or MVI.