Lower Index Of Microcirculatory Resistance Research Articles

The role of arginine vasopressin in the pathophysiology of microvascular dysfunction after ST-elevation myocardial infarction

Abstract Background Coronary microvascular dysfunction (CMD) after ST-elevation myocardial infarction (STEMI), in part due to impaired vasomotor tone, predicts heart failure and mortality at one year. Arginine vasopressin (AVP) may be implicated in CMD as it is released during MI and has known vasoconstrictor effects, but data in humans are lacking. We examined the role of copeptin, a stable plasma surrogate marker of AVP, in humans with STEMI. Methods We included three cohorts. The first cohort prospectively recruited patients presenting with STEMI eligible for primary percutaneous coronary intervention (PPCI) (n= 55). In this cohort, the index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured in the culprit artery at the end of the procedure. The second cohort included 45 patients from a sub-study of the CAPRI trial (Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary PCI; NCT02390674). In this cohort, patients underwent cardiac magnetic resonance (CMR) imaging at one and 12 weeks post-MI, allowing precise measurement of infarct size and microvascular obstruction (MVO), the imaging hallmark of CMD. Both cohorts had serum copeptin measured at four time points. The 3rd cohort included two patients undergoing trans-coronary alcohol ablation of septal hypertrophy (TASH). Serial copeptin measurements were performed in this cohort to assess copeptin release in an induced ischaemia setting. Results One hundred patients were included from both STEMI cohorts. Copeptin levels paralleled AVP plasma levels closely, with mean levels falling in the 24 hours after reperfusion from 92.5 pmol/L to 6.4 pmol/L, and this was mirrored in the TASH patients. Copeptin release wasinversely linked to admission diastolic blood pressure (DBP) (Spearman’s rho r= -0.431, p=0.001), but did not correlate with systolic blood pressure. Copeptin levels at 24 hours were significantly associated with high IMR (r=0.372, p=0.011) and low CFR (r=-0.467, p=0.001). Patients with IMR >40 also had significantly higher mean copeptin concentration at 24 hours than those with lower IMR (19.1 vs 7.1pmol/L, p=0.019, Figure 1). Finally, patients with MVO on early CMR showed a trend towards higher mean copeptin concentration at baseline, although this was not statistically significant. Notably, copeptin levels were not associated with infarct size on either early or late CMR. Conclusions Copeptin, and therefore AVP, is released secondary to acute myocardial ischaemia, particularly in response to reduced coronary perfusion, as evidenced by the inverse correlation with DBP, and normalises by 24 hours. However, evidence of CMD was seen in patients with persistently elevated copeptin at 24 hours, suggesting AVP may contribute to microcirculatory dysfunction. AVP receptor antagonists may represent a novel therapeutic option in patients with STEMI and evidence of microvascular dysfunction.

Predictive Efficacy of the Index of Microcirculatory Resistance for Acute Allograft Rejection and Cardiac Events After Heart Transplantation: A Systematic Review and Meta-Analysis.

In patients treated by heart transplantation, the index of microcirculatory resistance (IMR) has been found to have predictive potential for subsequent acute allograft rejection (AAR) and long-time cardiac events. When consulting related literature, the studies mostly were single-center with small sample sizes. The question of whether IMR can be utilized as a predictive biomarker is becoming increasingly contentious. To confirm the predictive efficacy of IMR, researchers did a systematic review and meta-analysis. From inception to April 2022, PubMed, EMBASE, Cochrane Library, Web of Science, Ovid, ProQuest, and Scopus systematically were searched. The results were presented as pooled ratio rate (RR) with 95% confidence intervals (CI). Assessment of the quality, heterogeneity analyses, and publication bias analysis also were performed. A total of 616 patients were studied in five trials. There were significant differences in subsequent AAR (RR = 4.08; 95% CI: 2.69~6.17; P = 0.000) or long-time cardiac events (RR=2.14; 95% CI: 1.44~3.19; P = 0.000) between IMR-high and IMR-low patients in the forest plots. Patients treated with heart transplantation in the high IMR group had better predictive efficacy than the low IMR group. High IMR could predict the events of subsequent AAR and cardiac events after heart transplantation. This will help reduce the occurrence of adverse events and personalize treatment for patients.

Abstract 10954: Quantification of Myocardial Perfusion Reserve Using a Cardiac-Centered Camera: First Comparison with Invasive Indexes of Coronary Microvascular Disease

Introduction: – The invasive quantification of coronary flow reserve (CFR), the index of microcirculatory resistance (IMR), and fractional flow reserve (FFR) allows to assess coronary physiology. Although semi-conductor (CZT) SPECT myocardial perfusion reserve (MPR) has been previously compared with FFR, there are no data documenting the relationships between CZT SPECT MPR on one hand and CFR and/or IMR on the other hand. We assessed the performances of noninvasive CZT SPECT MPR in comparison with invasively determined FFR, CFR, and IMR. Methods: – Rest and dipyridamole-induced stress myocardial blood flow and MPR were quantified using 99m Tc-SestaMIBI and a Discovery NM 530c camera in 26 patients with suspected or known coronary artery disease who underwent conventional invasive coronary angiography. Thermodilution-derived resting and adenosine-induced hyperemic mean transit times, distal intracoronary pressures, and mean aortic pressures were assessed for the quantification of FFR, CFR, and IMR values. Results: – Only 2/35 vessels presented with a pathological (<0.8) FFR. A moderate yet significant correlation was observed between regional CZT SPECT MPR and CFR (r=0.40, P =.02). The sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT SPECT MPR vs CFR were 69% [44-86%], 94% [74-100%], 91% [65-100%], 77% [56-90%], and 82% [65-93%], respectively. In territories without underlying CAD (n=32), CZT SPECT MPR values were significantly higher in those with CFR≥2 and IMR<25 (negative composite criterion, n=14) than in those with CFR<2 and IMR≥25 (positive composite criterion, n=8, CZT SPECT MPR, 2.6 [2.1-3.6] vs 1.6 [1.2-1.8]), P <.01). Regional CZT SPECT MPR displayed sensitivity, specificity, positive and negative predictive value, and accuracy of 87% [53-99%], 100% [78-100%], 100% [64-100%], 93% [70-99%], and 95% [77-99%] for the diagnosis of a positive composite criterion, respectively. Conclusions: – CZT SPECT MPR presented a moderate, significant correlation with thermodilution CFR and good diagnostic performances for the detection of patients at high risk of cardiovascular events (low CFR and high IMR) in the absence of obstructive CAD.

Coronary Microvascular Dysfunction Assessed by Pressure Wire and CMR After STEMI Predicts Long-Term Outcomes

ObjectivesThis study sought to evaluate the long-term prognostic implications of coronary microvascular dysfunction (CMD) when assessed with both cardiovascular magnetic resonance (CMR) and index of microcirculatory resistance (IMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). BackgroundPost-ischemic CMD can be assessed using the pressure-wire based IMR and/or by the presence of microvascular obstruction (MVO) on CMR. MethodsA total of 198 patients with STEMI underwent IMR and MVO assessment. Patients were classified as follows: Group 1, no significant CMD (low IMR [≤40 U] and no MVO); Group 2, CMD with either high IMR (>40 U) or MVO; Group 3, CMD with both IMR >40 U and MVO. The primary endpoint was the composite of all-cause mortality, diagnosis of new heart failure, cardiac arrest, sustained ventricular tachycardia/fibrillation, and cardioverter defibrillator implantation. ResultsCMD with both high IMR and MVO was present in 23.7% of the cases (Group 3) and CMD with either high IMR or MVO was observed in 40.9% of cases (Group 2). At a median follow-up of 40.1 months, the primary endpoint occurred in 34 (17%) cases. At 1 year of follow-up, Group 3 (hazard ratio [HR]: 12.6; 95% confidence interval [CI]: 1.6 to 100.6; p = 0.017) but not Group 2 (HR: 7.2; 95% CI: 0.9 to 57.9; p = 0.062) had worse clinical outcomes compared with those with no significant CMD in Group 1. However, in the long-term, patients in Group 2 (HR: 4.2; 95% CI: 1.4 to 12.5; p = 0.009) and those in Group 3 (HR: 5.2; 95% CI: 1.7 to 16.2; p = 0.004) showed similar adverse outcomes, mainly driven by the occurrence of heart failure. ConclusionsPost-ischemic CMD predicts a more than 4-fold increase in long-term risk of adverse outcomes, mainly driven by the occurrence of heart failure. Defining CMD by either invasive IMR >40 U or by CMR-assessed MVO showed similar risk of adverse outcomes.

Index of microcirculatory resistance predicts long term cardiac systolic function in patients with STEMI undergoing primary PCI

BackgroundTo evaluate the predictive value of the index of microcirculatory resistance (IMR) for long-term cardiac systolic function after primary percutaneous coronary intervention (pPCI) in patients with acute anterior wall ST-segment elevation myocardial infarction (STEMI).MethodsA total of 53 acute anterior wall STEMI patients were included and followed up within 1-year. IMR was measured to evaluate the immediate intraoperative reperfusion. IMR > 40 U was defined as the high IMR group and ≤ 40 U was defined as the low IMR group. Left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 h, 1 month, 3 months, and 1 year after PCI to analyze the correlation between IMR and cardiac systolic function. Heart failure was estimated according to classification within one year.ResultsThe ratio of TMPG (TIMI myocardial perfusion grade) 3 (85.7% vs. 52%, p = 0.015) and STR (ST-segment resolution) > 70% (82.1% vs. 48%, p = 0.019) were significantly higher in the low IMR group. The LVEF in the low IMR group was significantly higher than that in the high IMR group at 3 months (43.06 ± 2.63% vs. 40.20 ± 2.67%, p < 0.001) and 1 year (44.16 ± 2.40% vs. 40.13 ± 3.48%, p < 0.001). IMR was negatively correlated with LVEF at 3 months (r = − 0.1014, p = 0.0040) and 1 year (r = − 0.1754, p < 0.0001).ConclusionsThe IMR showed significant negative correlation with the LVEF value after primary PCI. The high IMR is a strong predictor of heart failure within 1 year after anterior myocardial infarction.

Risk Stratification Guided by the Index of Microcirculatory Resistance and Left Ventricular End-Diastolic Pressure in Acute Myocardial Infarction.

The index of microcirculatory resistance (IMR) of the infarct-related artery and left ventricular end-diastolic pressure (LVEDP) are acute, prognostic biomarkers in patients undergoing primary percutaneous coronary intervention. The clinical significance of IMR and LVEDP in combination is unknown. IMR and LVEDP were prospectively measured in a prespecified substudy of the T-TIME clinical trial (Trial of Low Dose Adjunctive Alteplase During Primary PCI). IMR was measured using a pressure- and temperature-sensing guidewire following percutaneous coronary intervention. Prognostically established thresholds for IMR (>32) and LVEDP (>18 mm Hg) were predefined. Contrast-enhanced cardiovascular magnetic resonance imaging (1.5 Tesla) was acquired 2 to 7 days and 3 months postmyocardial infarction. The primary end point was major adverse cardiac events, defined as cardiac death/nonfatal myocardial infarction/heart failure hospitalization at 1 year. IMR and LVEDP were both measured in 131 patients (mean age 59±10.7 years, 103 [78.6%] male, 48 [36.6%] with anterior myocardial infarction). The median IMR was 29 (interquartile range, 17-55), the median LVEDP was 17 mm Hg (interquartile range, 12-21), and the correlation between them was not statistically significant (r=0.15; P=0.087). Fifty-three patients (40%) had low IMR (≤32) and low LVEDP (≤18), 18 (14%) had low IMR and high LVEDP, 31 (24%) had high IMR and low LVEDP, while 29 (22%) had high IMR and high LVEDP. Infarct size (% LV mass), LV ejection fraction, final myocardial perfusion grade ≤1, TIMI (Thrombolysis In Myocardial Infarction) flow grade ≤2, and coronary flow reserve were associated with LVEDP/IMR group, as was hospitalization for heart failure (n=18 events; P=0.045) and major adverse cardiac events (n=21 events; P=0.051). LVEDP>18 and IMR>32 combined was associated with major adverse cardiac events, independent of age, estimated glomerular filtration rate, and infarct-related artery (odds ratio, 5.80 [95% CI, 1.60-21.22] P=0.008). The net reclassification improvement for detecting major adverse cardiac events was 50.6% (95% CI, 2.7-98.2; P=0.033) when LVEDP>18 was added to IMR>32. IMR and LVEDP in combination have incremental value for risk stratification following primary percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02257294.

Mechanical and Pharmacological Revascularization Strategies for Prevention of Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction: Analysis from Index of Microcirculatory Resistance Registry Data.

Objectives We aimed to identify mechanical and pharmacological revascularization strategies correlated with the index of microcirculatory resistance (IMR) in ST-elevation myocardial infarction (STEMI) patients. Background Microvascular dysfunction (MVD) after STEMI is correlated with infarct size and poor long-term prognosis, and the IMR is a useful analytical method for the quantitative assessment of MVD. However, therapeutic strategies that can reliably reduce MVD remain uncertain. Methods Patients with STEMI who underwent primary percutaneous coronary intervention (PCI) were enrolled. The IMR was measured with a pressure sensor/thermistor-tipped guidewire immediately after primary PCI. High IMR was defined as values ≥66th percentile of IMR in enrolled patients (IMR > 30.9 IU). Results A total of 160 STEMI patients were analyzed (high IMR = 54 patients). Clinical factors for Killip class (P=0.006), delayed hospitalization from symptom onset (P=0.004), peak troponin-I level (P=0.042), and multivessel disease (P=0.003) were associated with high IMR. Achieving final thrombolysis in myocardial infarction myocardial perfusion grade 3 tended to be associated with low IMR (P=0.119), whereas the presence of distal embolization was significantly associated with high IMR (P=0.034). In terms of therapeutic strategies that involved adjusting clinical and angiographic factors associated with IMR, preloading of third-generation P2Y12 inhibitors correlated with reducing IMR value (β = −10.30, P < 0.001). Mechanical therapeutic strategies including stent diameter/length, preballoon dilatation, direct stenting, and thrombectomy were not associated with low IMR value (all P > 0.05), and postballoon dilatation was associated with high IMR (β = 8.30, P=0.020). Conclusions In our study, mechanical strategies were suboptimal in achieving myocardial salvage. Preloading of third-generation P2Y12 inhibitors revealed decreased IMR value, indicative of MVD prevention.

Long-term Patient Prognostication by Coronary Flow Reserve and Index of Microcirculatory Resistance: International Registry of Comprehensive Physiologic Assessment.

Background and ObjectivesRecent guideline recommends evaluation using of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with functionally insignificant stenosis. We evaluated clinical implications of CFR and IMR in patients with high fractional flow reserve (FFR) and deferred revascularization.MethodsA total of 867 patients (1,152 vessels) consigned to deferred revascularization who underwent comprehensive physiologic assessments were enrolled. Patients with high FFR (>0.80) were categorized by CFR (≤2) and IMR (≥23 U). Clinical outcome was assessed by patient-oriented composite outcome (POCO), a composite of any death, myocardial infarction (MI), and revascularization at 5 years.ResultsPatients with low CFR (≤2) showed significantly greater risk of POCO than those with high CFR (>2) in both high-FFR (p=0.024) and low-FFR (p=0.034) groups. In patients with high FFR, those with low CFR and high IMR (overt microvascular disease) displayed the greatest risk of POCO overall (p=0.015), surpassing those with high CFR and low IMR (HR, 2.873; 95% CI, 1.476–5.594; p=0.002) and showing significantly greater risk of cardiac death or MI (HR, 5.662; 95% CI, 1.984–16.154; p=0.001). Overt microvascular disease was independently associated with POCO in the high-FFR population (HR, 2.282; 95% CI, 1.176–4.429; p=0.015).ConclusionAmong patients with deferred revascularization, those with low CFR showed significantly greater risk of POCO than those with high CFR, regardless of FFR. In patients with high FFR, those with overt microvascular disease showed significantly greater risk of POCO and cardiac death or MI at 5-year, compared with the others.Trial RegistrationClinicalTrials.gov Identifier: NCT03690713

Functional classification discordance in intermediate coronary stenoses between fractional flow reserve and angiography-based quantitative flow ratio

BackgroundMeasurement of the contrast-flow quantitative flow ratio (cQFR) is a novel method for rapid computational estimation of fractional flow reserve (FFR). Discordance between FFR and cQFR has not been completely...

Physiologic Characteristics and Clinical Outcomes of Patients With Discordance Between FFR and iFR

ObjectivesThis study evaluated the physiologic characteristics of discordant lesions between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) and the prognosis at 5 years. BackgroundFFR or iFR have been standard methods for assessing the functional significance of coronary artery stenosis. However, limited data exist about the physiologic characteristics of discordant lesions and the prognostic implications resulting from these lesions. MethodsA total of 840 vessels from 596 patients were classified according to iFR and FFR; high iFR–high FFR (n = 580), low iFR–high FFR (n = 40), high iFR–low FFR (n = 69), and low iFR–low FFR (n = 128) groups, which were compared with a control group (n = 23). The differences in coronary circulatory indices including the coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and resistance reserve ratio (RRR) (resting distal arterial pressure × mean transit time / hyperemic distal arterial pressure × hyperemic mean transit time), which reflect the vasodilatory capacity of coronary microcirculation, were compared. Patient-oriented composite outcomes (POCO) at 5 years including all-cause death, any myocardial infarction, and any revascularization were compared among patients with deferred lesions. ResultsIn the low iFR–high FFR group, CFR, RRR, and IMR measurements were similar to the low iFR–low FFR group: CFR 2.71 versus 2.43 (p = 0.144), RRR 3.36 versus 3.68 (p = 0.241), and IMR 18.51 versus 17.38 (p = 0.476). In the high iFR–low FFR group, the CFR, RRR, and IMR measurements were similar to the control group: CFR 2.95 versus 3.29 (p = 0.160), RRR 4.28 versus 4.00 (p = 0.414), and IMR 17.44 versus 17.06 (p = 0.818). Among the 4 groups, classified by iFR and FFR, CFR and RRR were all significantly different, except for IMR. However, there were no significant differences in the rates of POCO, regardless of discordance between the iFR and FFR. Only the low iFR–low FFR group had a higher POCO rate compared with the high iFR–high FFR group (adjusted hazard ratio: 2.46; 95% confidence interval: 1.17 to 5.16; p = 0.018). ConclusionsDifferences in coronary circulatory function were found, especially in the vasodilatory capacity between the low iFR–high FFR and high iFR–low FFR groups. FFR–iFR discordance was not related to an increased risk of POCO among patients with deferred lesions at 5 years. (Clinical, Physiological and Prognostic Implication of Microvascular Status;NCT02186093; Physiologic Assessment of Microvascular Function in Heart Transplant Patients; NCT02798731)

Index of microcirculatory resistance-guided therapy with pressure-controlled intermittent coronary sinus occlusion improves coronary microvascular function and reduces infarct size in patients with ST-elevation myocardial infarction: the Oxford Acute Myocardial Infarction - Pressure-controlled Intermittent Coronary Sinus Occlusion study (OxAMI-PICSO study).

The Oxford Acute Myocardial Infarction PICSO (OxAMI-PICSO) study aimed to assess the efficacy of index of microcirculatory resistance (IMR)-guided therapy with pressure-controlled intermittent coronary sinus occlusion (PICSO) in anterior ST-elevation myocardial infarction (STEMI). Patients with anterior STEMI treated with primary percutaneous coronary intervention (pPCI) were enrolled. Pre-stenting IMR was measured and PICSO treatment delivered if pre-stenting IMR was >40. No PICSO treatment was considered in patients with a pre-stenting IMR ≤40. The control group was derived from a historical cohort of STEMI patients with pre-stenting IMR >40 enrolled in the observational OxAMI study. IMR was measured after completion of pPCI in all patients and within 48 hours in PICSO patients and controls. Cardiac magnetic resonance imaging was performed per protocol for infarct size (IS) assessment within 48 hours after pPCI and at six months. A total of 105 patients were enrolled (25 PICSO, 50 controls with pre-stenting IMR >40, 30 with pre-stenting IMR ≤40). Compared to controls, patients treated with PICSO had a lower IMR at 24-48 hours (24.8 [18.5-35.9] vs. 45.0 [32.0-51.3], p<0.001) and lower IS at six months (26.0% [20.2-30.0] vs. 33.0% [28.0-37.0], p=0.006). An IMR-guided treatment with PICSO in anterior STEMI is feasible and may be associated with reduced IS and improved microvascular function.

Influence of Microcirculatory Dysfunction on Angiography-Based Functional Assessment of Coronary Stenoses

ObjectivesThe authors sought to evaluate the influence of coronary microcirculatory dysfunction (CMD) on the diagnostic performance of the quantitative flow ratio (QFR). BackgroundFunctional angiographic assessment of coronary stenoses based on fluid dynamics, such as QFR, constitutes an attractive alternative to fractional flow reserve (FFR). However, it is unknown whether CMD affects the reliability of angiography-based functional indices. MethodsFFR and the index of microcirculatory resistance (IMR) were measured in 300 vessels (248 patients) as part of a multicenter international registry. QFR was calculated at a blinded core laboratory. Vessels were classified into 2 groups according to microcirculatory status: low IMR (<23 U), and high IMR (≥23 U, CMD). The impact of CMD on the diagnostic performance of QFR, as well as on incremental value of QFR over quantitative angiography, was assessed using FFR as reference. ResultsPercent diameter stenosis (%DS) and FFR were similar in low- and high-IMR groups (%DS 51 ± 12% vs. 53 ± 11%; p = 0.16; FFR 0.80 ± 0.11 vs. 0.81 ± 0.11; p = 0.23, respectively). In the overall cohort, classification agreement (CA) between QFR and FFR and diagnostic efficiency of QFR (area under the receiver-operating characteristics curve [AUC]) were high (CA: 88%; AUC: 0.93 [95% confidence interval (CI): 0.90 to 0.96]). However, when assessed according to microcirculatory status, a significantly lower CA and AUC of QFR were found in the high-IMR group as compared with the low-IMR group (CA: 76% vs. 92%; p < 0.001; AUC: 0.88 [95% CI: 0.79 to 0.94] vs. 0.96 [95% CI: 0.92 to 0.98]; p < 0.05). Compared with angiographic assessment, QFR increased by 0.20 (p < 0.001) and by 0.16 (p < 0.001) the AUC of %DS in low- and high-IMR groups, respectively. Independent predictors of misclassification between QFR and FFR were high IMR and acute coronary syndrome. ConclusionsCMD decreases the diagnostic performance of QFR. However, even in the presence of CMD, QFR remains superior to angiography alone in ascertaining functional stenosis severity.

Coronary Flow Reserve and Microcirculatory Resistance in Patients With Intermediate Coronary Stenosis

BackgroundThe prognostic impact of microvascular status in patients with high fractional flow reserve (FFR) is not clear. ObjectivesThe goal of this study was to investigate the implications of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients who underwent FFR measurement. MethodsPatients with high FFR (>0.80) were grouped according to CFR (≤2) and IMR (≥23 U) levels: group A, high CFR with low IMR; group B, high CFR with high IMR; group C, low CFR with low IMR; and group D, low CFR with high IMR. Patient-oriented composite outcome (POCO) of any death, myocardial infarction, and revascularization was assessed. The median follow-up was 658 days (interquartile range: 503.8 to 1,139.3 days). ResultsA total of 313 patients (663 vessels) were assessed with FFR, CFR, and IMR. Correlation (r = 0.201; p < 0.001) and categorical agreement (kappa value = 0.178; p < 0.001) between FFR and CFR were modest. Low CFR was associated with higher POCO than high CFR (p = 0.034). There were no significant differences in clinical and angiographic characteristics among groups. Patients with high IMR with low CFR had the highest POCO (p = 0.002). Overt microvascular disease (p = 0.008), multivessel disease (p = 0.033), and diabetes mellitus (p = 0.033) were independent predictors of POCO. Inclusion of a physiological index significantly improved the discriminant function of a predictive model (relative integrated discrimination improvement 0.467 [p = 0.037]; category-free net reclassification index 0.648 [p = 0.007]). ConclusionsCFR and IMR improved the risk stratification of patients with high FFR. Low CFR with high IMR was associated with poor prognosis. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093)

The Index of Microcirculatory Resistance as a Predictor of Echocardiographic Left Ventricular Performance Recovery in Patients With ST-Elevation Acute Myocardial Infarction Undergoing Successful Primary Angioplasty.

This study aims to evaluate the relationship between IMR (Index of Microcirculatory Resistance) and the echocardiographic evolution of left ventricular (LV) systolic and diastolic performance after ST-elevation acute myocardial infarction (STEMI), undergoing primary angioplasty (P-PCI). IMR was evaluated immediately after P-PCI. Echocardiograms were performed within the first 24 hours (Echo1) and at 3 months (Echo2): LV volumes, ejection fraction (LVEF), wall motion score index (WMSI), E/é ratio, global longitudinal strain (GLS), and left atrial volume were measured. Forty STEMI patients were divided in 2 groups according to median IMR: Group 1 (IMR < 26), with less microvascular dysfunction, and Group 2 (IMR > = 26), with more microvascular dysfunction. In Echo1 GLS was significantly better in Group 1 (-14.9 vs. -12.9 in Group 2, P = 0.005). However, there were no significant differences between the two groups in LV systolic volume, LVEF and WMS. Between Echo1 and Echo2, there were significant improvements in LVEF (0.48 ± 0.06 vs. 0.55 ± 0.06, P < 0.0001), GLS (-14.9 ± 1.3 vs. -17.3 ± 7.6, P = 0.001), and E/é ratio (9.3 ± 3.4 vs. 8.2 ± 2.0, P = 0.037) in Group 1, but not in Group 2: LVEF (0.49 ± 0.06 vs. 0.50 ± 0.05, P = 0.47), GLS (-12.9 ± 2.4 vs. -14.4 ± 3.2, P = 0.052), and E/é ratio (8.8 ± 2.4 vs. 10.0 ± 4.7, P = 0.18). WMSI improved significantly more in Group 1 (reduction of -17.1% vs. -6.8% in Group 2, P = 0.015). Lower IMR was associated with better myocardial GLS acutely after STEMI, and with a significantly higher recovery of the LVEF, WMSI, E/E' ratio and GLS, suggesting that IMR is an early marker of cardiac recovery, after acute myocardial infarction.

Serial assessment of the index of microcirculatory resistance during primary percutaneous coronary intervention comparing manual aspiration catheter thrombectomy with balloon angioplasty (IMPACT study): a randomised controlled pilot study

ObjectiveUtilising a novel study design, we evaluated serial measurements of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI)...

Clinical and Angiographic Predictors of Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction.

PurposeWe aimed to discover clinical and angiographic predictors of microvascular dysfunction using the index of microcirculatory resistance (IMR) in patients with ST-segment elevation myocardial infarction (STEMI).Materials and MethodsWe enrolled 113 patients with STEMI (age, 56±11 years; 95 men) who underwent primary percutaneous coronary intervention (PCI). The IMR was measured with a pressure sensor/thermistor-tipped guidewire after primary PCI. The patients were divided into three groups based on IMR values: Low IMR [<18 U (12.9±2.6 U), n=38], Mid IMR [18-31 U (23.9±4.0 U), n=38], and High IMR [>31 U (48.1±17.1 U), n=37].ResultsThe age of the Low IMR group was significantly lower than that of the Mid and High IMR groups. The door-to-balloon time was <90 minutes in all patients, and it was not significantly different between groups. Meanwhile, the symptom-onset-to-balloon time was significantly longer in the High IMR group, compared to the Mid and Low IMR groups (p<0.001). In the high IMR group, the culprit lesion was found in a proximal location significantly more often than in a non-proximal location (p=0.008). In multivariate regression analysis, age and symptom-onset-to-balloon time were independent determinants of a high IMR (p=0.013 and p=0.003, respectively).ConclusionOur data suggest that age and symptom-onset-to-balloon time might be the major predictors of microvascular dysfunction in STEMI patients with a door-to-balloon time of <90 minutes.

Low Coronary Microcirculatory Resistance Associated With Profound Hypotension During Intravenous Adenosine Infusion

Intravenous adenosine infusion produces coronary and systemic vasodilatation, generally leading to systemic hypotension. However, adenosine-induced hypotension during stable hyperemia is heterogeneous, and its relevance to coronary stenoses assessment with fractional flow reserve (FFR) remains largely unknown. FFR, coronary flow reserve, and index of microcirculatory resistance were measured in 93 stenosed arteries (79 patients). Clinical and intracoronary measurements were analyzed among tertiles of the percentage degree of adenosine-induced hypotension, defined as follows: %ΔP(a)=-[100-(hyperemic aortic pressure×100/baseline aortic pressure)]. Overall, %ΔP(a) was -13.6±12.0%. Body mass index was associated with %ΔP(a) (r=0.258; P=0.025) and obesity, an independent predictor of profound adenosine-induced hypotension (tertile 3 of %ΔP(a); odds ratio, 3.95 [95% confidence interval, 1.48-10.54]; P=0.006). %ΔP(a) was associated with index of microcirculatory resistance (ρ=0.311; P=0.002), coronary flow reserve (r=-0.246; P=0.017), and marginally with FFR (r=0.203; P=0.051). However, index of microcirculatory resistance (β=0.003; P<0.001) and not %ΔP(a) (β=-0.001; P=0.564) was a predictor of FFR. Compared with tertiles 1 and 2 of %ΔP(a) (n=62 [66.6%]), stenoses assessed during profound adenosine-induced hypotension (n=31 [33.3%]) had lower index of microcirculatory resistance (12.4 [8.6-22.7] versus 20 [15.8-35.5]; P=0.001) and FFR values (0.77±0.13 versus 0.83±0.12; P=0.021), as well as a nonsignificant increase in coronary flow reserve (2.5±1.1 versus 2.2±0.87; P=0.170). The modification of systemic blood pressure during intravenous adenosine infusion is related to hyperemic microcirculatory resistance in the heart. Profound adenosine-induced hypotension is associated with obesity, lower coronary microcirculatory resistance, and lower FFR values.

The randomized physiologic assessment of thrombus aspirtion in patients with ST-segment Elevation acute Myocardial Infarction trial (PATA STEMI)

Background: Routine thrombus aspiration is superior to conventional primary Percutaneous Coronary Intervention (PCI) in terms of improved myocardial perfusion in patients with acute myocardial infarction with ST-segment Elevation (STEMI). However, myocardial perfusion after thrombus aspiration has not been evaluated by a quantitative Index of Microcirculatory Resistance (IMR). Methods: We performed a randomized, controlled clinical trial to evaluate impact of manual thrombus aspiration (the Eliminate aspiration catheter, Terumo Medical Supply, Japan) on microcirculatory resistance after primary PCI in 128 patients with the first STEMI randomly assigned to thrombus aspiration or conventional primary PCI group before coronary angiography. The primary endpoint was defined as a significant reduction of IMR in thrombus aspiration compared to conventional PCI group. Myocardial perfusion grade and resolution of ST-segment elevation were also assessed. Infarct size and left ventricle remodeling were assessed by echocardiographic indices. Results: Manual thrombus aspiration, as compared with conventional PCI, resulted in significantly lower IMR (31.9±21.3 U vs. 47.0±35.8 U, P = 0.0082). Treatment with thrombus aspiration, as compared with conventional PCI, resulted in similar rates of myocardial perfusion grade 0 or 1 (20.8% vs. 29.4%; relative risk, 0.71; 95% CI, 0.38 to 1.30; P=0.26) and complete resolution of ST-segment elevation (59.7% vs. 47.1%; relative risk, 1.27; 95% CI, 0.90 to 1.79, P=0.17). In a multiple regression model with the log-transformed IMR as dependent variable, after adjusting for clinical, angiographic and procedural variables, thrombus aspiration remained a strong independent predictor of lower IMR (27.14 U; 95% CI, 23.79 to 30.95 U, vs. 36.11 U; 95% CI, 30.74 to 42.41 U, P=0.0076). Histopathological examination confirmed successful thrombus aspiration in 89.6% of patients. The results of echocardiographic analysis will be available at the time of the presentation. Conclusions: Manual thrombus aspiration reduces microcirculatory resistance indicating better myocardial perfusion compared to conventional PCI in patients with STEMI.

Acute Effect of Sodium Nitroprusside on Microvascular Dysfunction in Patients Who Underwent Percutaneous Coronary Intervention for Acute ST-segment Elevation Myocardial Infarction

Even in the era of thrombus aspiration and distal protection for ST-segment elevation acute myocardial infarction (STEMI), microvascular dysfunction does exist and improvement of microvascular dysfunction can improve the prognosis and/or left ventricular dysfunction. We evaluated the acute effects of nitroprusside (NTP) on coronary microvascular injury that occurred after primary percutaneous coronary intervention (PCI) for STEMI in 18 patients. The final Thrombolysis in Myocardial Infarction trial (TIMI) flow grade after PCI was 3 in 17 patients and 2 in 1 patient. The index of microcirculatory resistance (IMR) was improved significantly from 76 ± 42 to 45 ± 37 (P = 0.0006) by intracoronary NTP administration. IMR improved to the normal range (IMR < 30) in 9 patients (50%). Higher TIMI flow grade and lower IMR at baseline were observed more frequently in patients whose IMR recovered to normal range after NTP administration. NTP improved the microcirculatory dysfunction at the acute phase in patients who underwent PCI for STEMI and had final TIMI 3 flow in almost all cases.

The Impact of Pravastatin Pre-Treatment on Periprocedural Microcirculatory Damage in Patients Undergoing Percutaneous Coronary Intervention

This study evaluated the effect of pravastatin pre-treatment on post-procedural index of microcirculatory resistance (IMR) values that are introduced for assessing the status of the microcirculation independently of the epicardial area. Pre-treatment with statins decreased the incidence of cardiac enzyme increase after percutaneous coronary intervention (PCI). However, 2 different etiologies, distal embolization of atheroma or ischemia caused by side-branch occlusion, cannot be differentiated by measuring cardiac enzyme levels. Eighty patients with stable angina were randomly assigned to either pravastatin treatment (20 mg/day, n = 40) or no treatment (n = 40) 4 weeks before elective PCI. An intracoronary pressure/temperature sensor-tipped guidewire was used. Thermodilution curves were obtained during maximal hyperemia. The IMR was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time. Creatine kinase-myocardial band and troponin I values were measured at baseline and at 8 and 24 h after PCI. Post-PCI troponin I levels tended to be lower in patients with pravastatin treatment (median: 0.13 [interquartile range (IQR): 0.10 to 0.31] vs. 0.22 [IQR: 0.10 to 0.74] ng/ml, p = 0.1). However, patients with pravastatin treatment had significantly lower IMR than did patients without pravastatin treatment (median: 12.6 [IQR: 8.8 to 18.0] vs. 17.6 [IQR: 9.7 to 33.9], p = 0.007). Multivariate analysis revealed that the lack of pravastatin pre-treatment was the only independent predictor of post-PCI impaired IMR (p = 0.03). Post-PCI measurement of the IMR confirmed that pre-treatment with pravastatin was associated with reduced microvascular dysfunction induced by PCI regardless of side branch occlusions. These data suggest that pre-treatment with statin is desired in patients undergoing elective PCI. (The Impact of Pravastatin Pretreatment on Periprocedural Microcirculatory Damage After Percutaneous Coronary Intervention; UMIN000002885).