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Diagram showing patient recruitment, randomization, and flow through the T-TIME physiology substudy. CMR indicates cardiovascular magnetic resonance; STEMI, ST-segment-elevation myocardial infarction; T-TIME, A Trial of LowDose Adjunctive Alteplase During Primary PCI.
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Background
Impaired microcirculatory reperfusion worsens prognosis following acute ST ‐segment–elevation myocardial infarction. In the T‐ TIME (A Trial of Low‐Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low‐dose, intracoronary alteplase (...
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Background
We systematically reviewed trials comparing different reperfusion strategies for ST‐segment–elevation myocardial infarction and used multivariate network meta‐analysis to compare outcomes across these strategies.
Methods and Results
We identified 31 contemporary trials in which patients with ST‐segment–elevation myocardial infarction we...
Citations
... In this case, the terms "no-reflow" or "MVO" are used as synonyms. There is a correlation between TIMI evaluated angiographically and the MVO size measured by magnetic resonance imaging (MRI) [10,11]. In a study of patients with AMI and PCI it was found that the duration of cardiac ischemia and infarct size are major determinant of severe MVO [12][13][14][15]. ...
... The intramyocardial hemorrhage (IMH) area was 3.8% of LV mass in patients with STEMI and MVO after PCI [11]. Currently, the assessment of MVO often uses both angiography and MRI (Table 1, Ref. [5,7,[9][10][11][12][13][14][16][17][18]). However, in recent years, investigators increasingly favor MRI as a more accurate method of assessing MVO. ...
... However, in recent years, investigators increasingly favor MRI as a more accurate method of assessing MVO. Angiographic parameters are more variable ( Table 2, Ref. [5,7,[9][10][11]18,[23][24][25][26][27][28][29][30][31][32][34][35][36]38,39,43,44,71]). Sardu et al. [72] found that prediabetes promotes the disorder of acetylcholine-induced coronary vasodilation and major adverse cardiac events in patients with non-obstructive coronary stenosis. ...
... There was no effect of alteplase at either dose on microvascular obstruction as measured on CMR imaging [47]. There was no difference in bleeding events, cardiac death, hospitalization for heart failure or MACE events measured at one year [48]. The ICE-T-TIMI-49 study randomized STEMI patients to a volume matched bolus of IC TNK (4 mg) (n = 20) or saline placebo (n = 20) before and following PPCI. ...
... The largest such study, T-TIME, randomized 440 patients with proximal or mid vessel occlusion in a 1:1:1 fashion to IC delivery of alteplase (20 mg), alteplase (10 mg) or placebo immediately after reperfusion and prior to stent implantation. There was no effect of alteplase at either dose on microvascular obstruction, cardiac death, hospitalization for heart failure or MACE measured at one year [48]. ...
Introduction:
Large thrombus burden in patients with ST elevation myocardial infarction (STEMI) is associated with higher rates of distal embolization, no-reflow phenomenon, abrupt closure, stent thrombosis, major adverse cardiovascular events (MACE), and mortality. Intracoronary (IC) thrombolytic agents are theoretically attractive as an adjunct to primary percutaneous coronary intervention (PPCI) as they activate endogenous fibrinolysis which results in degradation of the cross-linked fibrin matrix in coronary thrombus.
Areas covered:
We reviewed published studies reporting on intraprocedural anti-thrombus strategies used during PPCI including randomized controlled trials and observational studies.
Expert opinion:
Published studies are limited by small sample size and heterogeneity due to variation in indication, inclusion criteria, thrombolytic agent, dose, delivery mechanisms, antiplatelet and anticoagulant regimen, timing in regard to reperfusion, PCI techniques and endpoints. Despite these limitations, data are consistent that IC administration of thrombolytic agents at low doses is associated with low rates of bleeding and vascular complications. While there is currently no compelling data demonstrating a benefit to the routine use of IC thrombolytic therapy in patients with STEMI, there is suggestive data that IC thrombolysis may have benefit in selected patients.
... They represented no reduction in microvascular obstruction as well as an insignificant decrease in the incidence of major adverse cardiovascular events including cardiac death, nonfatal MI, and unplanned hospitalization for heart failure 13 . Similarly, the investigation by Maznyczka and colleagues on STEMI patients who were allocated to three groups of placebo, low dose (10 mg), and high dose (20 mg) alteplase declared no difference in microvascular myocardial function considering TIMI score, index of microcirculatory resistance, and resistive reserve ratio measured immediately after PPCI 20 . Those who oppose this strategy have reversal theories. ...
... It is reported that in most patients with STEMI the vasodilatory capacity of the microvascular coronary bed is blunted and consequently the response of coronary microcirculation to adenosine is often minimal or incomplete. (12,13). In this regard, we have recently described the non-hyperaemic version of IMR angio -NH IMR angio , and shown it retains its diagnostic reliability in most patients with STEMI (14). ...
... As a confirmation of this hypothesis, in our cohort, the median value of RRRa dedicated index to express the vasodilatory capacity of the coronary microcirculation-was 1.7. This value is suggestive of a depressed coronary microvascular vasodilatory capacity in this cohort of patients with STEMI, a finding consistent with previous reports (12,13). This depressed vasodilatory capacity can explain why, particularly in patients with STEMI, a non-hyperaemic index such as NH IMR angio retains some diagnostic accuracy in identifying microvascular injury (14). ...
Aims
Despite the prognostic value of coronary microvascular dysfunction (CMD) in patients with ST-segment-elevation myocardial infarction (STEMI), its assessment with pressure-wire-based methods remains limited due to cost, technical and procedural complexities. The non-hyperaemic angiography-derived index of microcirculatory resistance (NH IMRangio) has been shown to reliably predict microvascular injury in patients with STEMI. We investigated the prognostic potential of NH IMRangio as a pressure-wire and adenosine-free tool.
Methods and Results
NH IMRangio was retrospectively derived on the infarct-related artery at completion of primary percutaneous coronary intervention (pPCI) in 262 prospectively recruited STEMI patients. Invasive pressure-wire-based assessment of the index of microcirculatory resistance (IMR) was performed. The combination of all-cause mortality, resuscitated cardiac arrest and new heart failure was the primary endpoint.
NH IMRangio showed good diagnostic performance in identifying CMD (IMR >40U); AUC 0.78 (95%CI: 0.72-0.84, p<0.0001) with an optimal cut-off at 43U. The primary endpoint occurred in 38 (16%) patients at a median follow-up of 4.2 (2.0-6.5) years. On survival analysis, NH IMRangio >43U (log-rank test, p<0.001) was equivalent to an IMR >40U(log-rank test, p=0.02) in predicting the primary endpoint (hazard ratio comparison p-value=0.91). NH IMRangio >43U was an independent predictor of the primary endpoint(adjusted HR 2.13, 95%CI: 1.01-4.48, p=0.047).
Conclusion
NH IMRangio is prognostically equivalent to invasively measured IMR and can be a feasible alternative to IMR for risk stratification in patients presenting with STEMI.
Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41–50 % of patients with ST-segment elevation myocardial infarction and PCI and is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO, which is associated with infarct size, the duration of ischemia, and myocardial edema. However, there is no conclusive evidence that the latter plays an important role in the development of MVO. There is evidence that platelets, inflammation, Ca2+ overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell dysfunction in MVO formation in patients with AMI and PCI remains under question. It is unclear whether nitric oxide production is decreased in patients with MVO. It was obtained only indirect evidence on the involvement of inflammation in the development of MVO. The role of reactive oxygen species, necroptosis and pyroptosis in the pathogenesis of MVO is also not studied. The participation of thromboxane A2, vasopressin, and prostacyclin in the formation of MVO is unknown. It was not obtained conclusive evidence on the involvement of coronary artery spasm in the development of MVO. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type Ca2+-channel blockers improves coronary blood flow in patients with MVO.
Background
Microvascular obstruction (MVO) is an independent predictor of adverse cardiac events after ST‐elevation myocardial infarction (STEMI). The Index of Microcirculatory Resistance (IMR) may be a useful marker of MVO, which could simplify the care pathway without the need for Cardiac Magnetic Resonance (CMR). We assessed whether the IMR can predict MVO in STEMI patients.
Methods and Results
We conducted a systematic review and meta‐analysis, including articles where invasive IMR was performed post primary percutaneous coronary intervention (PCI) in addition to MVO assessment with cardiac MRI. We searched PubMed, Scopus, Embase, and Cochrane databases from inception until January 2023. Baseline characteristics, coronary physiology and cardiac MRI data were extracted by two independent reviewers. The random‐effects model was used to pool the data. Among 15 articles identified, nine articles ( n = 728, mean age 61, 81% male) contained IMR data stratified by MVO. Patients with MVO had a mean IMR of 41.2 [95% CI 32.4−50.4], compared to 25.3 [18.3−32.2] for those without. The difference in IMR between those with and without MVO was 15.1 [9.7−20.6]. Meta‐regression analyses demonstrated a linear relationship between IMR and TIMI grade ( β = 0.69 [0.13−1.26]), as well as infarct size ( β = 1.18 [0.24−2.11]) or ejection fraction at 6 months ( β = −0.18 [−0.35 to −0.01]).
Conclusion
In STEMI, patients with MVO had 15‐unit higher IMR than those without. IMR also predicts key prognostic endpoints such as infarct size, MVO, and long‐term systolic function.
Background and aims:
No-reflow (NR), where the coronary artery is patent after treatment of ST-elevation myocardial infarction (STEMI) but tissue perfusion is not restored, is associated with worse outcomes. We aimed to investigate the relationship between autoantibodies activating endothelin-1 receptor type A (ETAR-AAs) and NR after primary percutaneous coronary intervention (PPCI) in STEMI.
Methods:
We studied 50 patients (age 59 ± 11 years, 40 males) with STEMI who underwent PPCI within 6 h after the onset of symptoms. Blood samples were obtained from all patients within 12 h following PPCI for ETAR-AA level measurement. The seropositive threshold was provided by the manufacturer (>10 U/ml). NR was assessed by cardiac magnetic resonance imaging (MVO, microvascular obstruction). As a control group, 40 healthy subjects matched for age and sex were recruited from the general population.
Results:
MVO was observed in 24 patients (48%). The prevalence of MVO was higher in patients with ETAR-AAs seropositivity (72% vs. 38%, p = 0.03). ETAR-AAs were higher in patients with MVO (8.9 U/mL (interquartile range [IQR] 6.8-16.2 U/mL) vs. 5.7 U/mL [IQR 4.3-7.7 U/mL], p = 0.003). ETAR-AAs seropositivity was independently associated with MVO (OR 3.2, 95% CI 1.3-7.1; p = 0.03). We identified ≥6.74 U/mL as the best cut-off for prediction of MVO (sensitivity 79%; specificity 65%; NPV 71%; PPV 74%; accuracy 72%).
Conclusions:
The ETAR-AAs seropositivity is associated with NR in STEMI patients. These findings may open up new options in the management of myocardial infarction even if confirmation in a larger trial is needed.
Aims
We set out to further develop reflectance spectroscopy for the characterisation and quantification of coronary thrombi. Additionally, we explore the potential of our approach for use as a risk stratification tool by exploring the relation of reflectance spectra to indices of coronary microvascular injury.
Methods and results
We performed hyperspectral imaging of coronary thrombi aspirated from 306 patients presenting with ST-segment elevation acute coronary syndrome (STEACS). Spatially resolved reflected light spectra were analysed using unsupervised machine learning approaches. Invasive [index of coronary microvascular resistance (IMR)] and non-invasive [microvascular obstruction (MVO) at cardiac magnetic resonance imaging] indices of coronary microvascular injury were measured in a sub-cohort of 36 patients. The derived spectral signatures of coronary thrombi were correlated with both invasive and non-invasive indices of coronary microvascular injury. Successful machine-learning-based classification of the various thrombus image components, including differentiation between blood and thrombus, was achieved when classifying the pixel spectra into 11 groups. Fitting of the spectra to basis spectra recorded for separated blood components confirmed excellent correlation with visually inspected thrombi. In the 36 patients who underwent successful thrombectomy, spectral signatures were found to correlate well with the index of microcirculatory resistance and microvascular obstruction; R ² : 0.80, p < 0.0001, n = 21 and R ² : 0.64, p = 0.02, n = 17, respectively.
Conclusion
Machine learning assisted reflectance spectral analysis can provide a measure of thrombus composition and evaluate coronary microvascular injury in patients with STEACS. Future work will further validate its deployment as a point-of-care diagnostic and risk stratification tool for STEACS care.
Objectives
This study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure.
Background
A cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI).
Methods
The Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score.
Results
There were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score.
Conclusions
This noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).
Despite routinely restoring epicardial coronary patency, with primary percutaneous coronary intervention (PCI), microvascular obstruction affects approximately half of patients and confers an adverse prognosis. There are no evidence-based treatments for microvascular obstruction. A key contributor to microvascular obstruction is distal embolisation and microvascular thrombi. Adjunctive intracoronary fibrinolytic therapy may reduce thrombotic burden, potentially reducing distal embolisation of atherothrombotic debris to the microcirculation. In this review, the evidence from published randomised trials on the effects of adjunctive intracoronary fibrinolytic therapy during primary PCI is critically appraised, the ongoing randomised trials are described, and conclusions are made from the available evidence. Clinical uncertainties, to be addressed by future research, are highlighted.
