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 43U (log-rank test, p 40U(log-rank test, p = 0.02) in predicting the primary endpoint (hazard ratio comparison p = 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.

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Long-Term Clinical Outcomes in Patients With an Acute ST-Segment-Elevation Myocardial Infarction Stratified by Angiography-Derived Index of Microcirculatory Resistance.

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.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).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.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.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). 

A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction.

Objectives Persistently impaired culprit artery flow ( Methods In T-TIME (trial of low-dose adjunctive alTeplase during primary PCI), patients ≤6 hours from onset of ST-elevation myocardial infarction (STEMI) were randomised to placebo, alteplase 10 mg or alteplase 20 mg, administered by infusion into the culprit artery, pre-stenting. In this prespecified, secondary analysis, coronary flow was assessed angiographically at the point immediately before drug administration. Microvascular obstruction, myocardial haemorrhage and infarct size were assessed by cardiovascular magnetic resonance (CMR) at 2–7 days and 3 months. Results TIMI flow was assessed after first treatment (balloon angioplasty/aspiration thrombectomy), immediately pre-drug administration, in 421 participants (mean age 61±10 years, 85% male) and was 3, 2 or 1 in 267, 134 and 19 participants respectively. In patients with TIMI flow ≤2 pre-drug, there was higher incidence of microvascular obstruction with alteplase (alteplase 20 mg (53.1%) and 10 mg (59.5%) combined versus placebo (34.1%); OR=2.47 (95% CI 1.16 to 5.22, p=0.018) interaction p=0.005) and higher incidence of myocardial haemorrhage (alteplase 20 mg (53.1%) and 10 mg (57.9%) combined vs placebo (27.5%); OR=3.26 (95% CI 1.44 to 7.36, p=0.004) interaction p=0.001). These effects were not observed in participants with TIMI 3 flow pre-drug. There were no interactions between TIMI flow pre-drug, alteplase and 3-month CMR findings. Conclusion In patients with impaired culprit artery flow ( Trial registration number NCT02257294.

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Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial.

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.

Adjunctive Intracoronary Fibrinolytic Therapy During Primary Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) is an expanding treatment option for patients with coronary artery disease (CAD). It is considered the default strategy for the unstable presentation of CAD. PCI techniques have evolved over the last 4 decades with significant improvements in stent design, an increase in functional assessment of coronary lesions, and the use of intra-vascular imaging. Nonetheless, the morbidity and mortality related to CAD remain significant. Advances in technology have allowed a better understanding of the nature and progression of CAD. New tools are now available that reflect the pathophysiological changes at the level of the myocardium and coronary atherosclerotic plaque. Certain changes within the plaque would render it more prone to rupture leading to acute vascular events. These changes are potentially detected using novel tools invasively, such as near infra-red spectroscopy, or non-invasively using T2 mapping cardiovascular magnetic resonance imaging (CMR) and 18F-Sodium Fluoride positron emission tomography/ computed tomography. Similarly, changes at the level of the injured myocardium are feasibly assessed invasively using index microcirculatory resistance or non-invasively using T1 mapping CMR. Importantly, these changes could be detected immediately with the opportunity to tailor treatment to those considered at high risk. Concurrently, novel therapeutic options have demonstrated promising results in reducing future cardiovascular risks in patients with CAD. This Review article will discuss the role of these novel tools and their applicability in employing a mechanical and pharmacological treatment to mitigate cardiovascular risk in patients with CAD. 

Novel Applications for Invasive and Non-invasive Tools in the Era of Contemporary Percutaneous Coronary Revascularisation

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...

Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction

This article traces the development of automated electrocardiography from its beginnings in Washington, DC around 1960 through to its current widespread application worldwide. Changes in the methodology of recording ECGs in analogue form using sizeable equipment through to digital recording, even in wearables, are included. Methods of analysis are considered from single lead to three leads to twelve leads. Some of the influential figures are mentioned while work undertaken locally is used to outline the progress of the technique mirrored in other centres. Applications of artificial intelligence are also considered so that the reader can find out how the field has been constantly evolving over the past 50 years.

Julie Kennedy

Papers

Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction

Automated ECG Interpretation—A Brief History from High Expectations to Deepest Networks