Sam Dawkins

How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction?

Aims Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with ST-elevation myocardial infarction (STEMI). An elevated index of microcirculatory resistance (IMR) reflects microvascular function and when measured after PPCI, it can predict an adverse clinical outcome. We measured coronary microvascular function in STEMI patients and compared sequential changes before and after stent implantation. Methods and results In 85 STEMI patients, fractional flow reserve, coronary flow reserve, and IMR were measured using a pressure wire (Certus, St Jude Medical, St Paul, MN, USA) immediately before and after stent implantation. Stenting significantly improved all of the measured parameters of coronary physiology including IMR from 67.7 [interquartile range (IQR): 56.2–95.8] to 36.7 (IQR: 22.7–59.5), P < 0.001. However, after stenting, IMR remained elevated (>40) in 28 (32.9%) patients. In 15 of these patients (17.6% of the cohort), only a partial reduction in IMR occurred and these patients were more likely to be late presenters (pain to wire time >6 h). The extent of jeopardized myocardium [standardized beta: −0.26 (IMR unit/Bypass Angioplasty Revascularization Investigation score unit), P: 0.009] and pre-stenting IMR [standardized beta: −0.34 (IMR unit), P: 0.001] predicted a reduction in IMR after stenting (ΔIMR = post-stenting IMR − pre-stenting IMR), whereas thrombotic burden [standardized beta: 0.24 (IMR unit/thrombus score unit), P: 0.01] and deployed stent volume [standardized beta: 0.26 (IMR unit/mm3 of stent), P: 0.01] were associated with a potentially deleterious increase in IMR. Conclusion Improved perfusion of the myocardium by stent deployment during PPCI is not universal. The causes of impaired microvascular function at the completion of PPCI treatment are heterogeneous, but can reflect a later clinical presentation and/or the location and extent of the thrombotic burden.

CMR Native T1 Mapping Allows Differentiation of Reversible Versus Irreversible Myocardial Damage in ST-Segment-Elevation Myocardial Infarction: An OxAMI Study (Oxford Acute Myocardial Infarction).

Background— CMR T1 mapping is a quantitative imaging technique allowing the assessment of myocardial injury early after ST-segment–elevation myocardial infarction. We sought to investigate the ability of acute native T1 mapping to differentiate reversible and irreversible myocardial injury and its predictive value for left ventricular remodeling. Methods and Results— Sixty ST-segment–elevation myocardial infarction patients underwent acute and 6-month 3T CMR, including cine, T2-weighted (T2W) imaging, native shortened modified look-locker inversion recovery T1 mapping, rest first pass perfusion, and late gadolinium enhancement. T1 cutoff values for oedematous versus necrotic myocardium were identified as 1251 ms and 1400 ms, respectively, with prediction accuracy of 96.7% (95% confidence interval, 82.8% to 99.9%). Using the proposed threshold of 1400 ms, the volume of irreversibly damaged tissue was in good agreement with the 6-month late gadolinium enhancement volume (r=0.99) and correlated strongly with the log area under the curve troponin (r=0.80) and strongly with 6-month ejection fraction (r=−0.73). Acute T1 values were a strong predictor of 6-month wall thickening compared with late gadolinium enhancement. Conclusions— Acute native shortened modified look-locker inversion recovery T1 mapping differentiates reversible and irreversible myocardial injury, and it is a strong predictor of left ventricular remodeling in ST-segment–elevation myocardial infarction. A single CMR acquisition of native T1 mapping could potentially represent a fast, safe, and accurate method for early stratification of acute patients in need of more aggressive treatment. Further confirmatory studies will be needed.

A tool for predicting the outcome of reperfusion in ST-elevation myocardial infarction using age, thrombotic burden and index of microcirculatory resistance (ATI score).

AIMS Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction is difficult to predict. A method to assess the likelihood of a suboptimal response to conventional pharmacomechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI. METHODS AND RESULTS A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) >40 was initially derived in a cohort of 85 STEMI patients (derivation cohort). This score was then tested and validated in three further cohorts of patients (retrospective [30 patients], prospective [42 patients] and external [29 patients]). The ATI score (age [>50=1]; pre-stenting IMR [>40 and <100=1; ≥100=2]; thrombus score [4=1; 5=3]) was highly predictive of a post-stenting IMR >40 in all four cohorts (AUC: 0.87; p<0.001-derivation cohort, 0.84; p=0.002-retrospective cohort, 0.92; p<0.001-prospective cohort and 0.81; p=0.006-external cohort). In the whole population, an ATI score ≥4 presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred in the presence of an ATI score <2. CONCLUSIONS The ATI score appears to be a promising tool capable of identifying patients during PPCI who are at the highest risk of coronary microvascular impairment following revascularisation. This procedural risk stratification has a number of potential research and clinical applications and warrants further investigation.

Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction

Transcriptionally activated monocytes are recruited to the heart after acute myocardial infarction (AMI). After AMI in mice and humans, the number of extracellular vesicles (EVs) increased acutely. In humans, EV number correlated closely with the extent of myocardial injury. We hypothesized that EVs mediate splenic monocyte mobilization and program transcription following AMI. Some plasma EVs bear endothelial cell (EC) integrins, and both proinflammatory stimulation of ECs and AMI significantly increased VCAM-1–positive EV release. Injected EC-EVs localized to the spleen and interacted with, and mobilized, splenic monocytes in otherwise naive, healthy animals. Analysis of human plasma EV-associated miRNA showed 12 markedly enriched miRNAs after AMI; functional enrichment analyses identified 1,869 putative mRNA targets, which regulate relevant cellular functions (e.g., proliferation and cell movement). Furthermore, gene ontology termed positive chemotaxis as the most enriched pathway for the miRNA-mRNA targets. Among the identified EV miRNAs, EC-associated miRNA-126-3p and -5p were highly regulated after AMI. miRNA-126-3p and -5p regulate cell adhesion– and chemotaxis-associated genes, including the negative regulator of cell motility, plexin-B2. EC-EV exposure significantly downregulated plexin-B2 mRNA in monocytes and upregulated motility integrin ITGB2. These findings identify EVs as a possible novel signaling pathway by linking ischemic myocardium with monocyte mobilization and transcriptional activation following AMI.

Metabolomic Profiling in Acute ST‐Segment–Elevation Myocardial Infarction Identifies Succinate as an Early Marker of Human Ischemia–Reperfusion Injury

Background Ischemia–reperfusion injury following ST‐segment–elevation myocardial infarction (STEMI) is a leading determinant of clinical outcome. In experimental models of myocardial ischemia, succinate accumulation leading to mitochondrial dysfunction is a major cause of ischemia–reperfusion injury; however, the potential importance and specificity of myocardial succinate accumulation in human STEMI is unknown. We sought to identify the metabolites released from the heart in patients undergoing primary percutaneous coronary intervention for emergency treatment of STEMI. Methods and Results Blood samples were obtained from the coronary artery, coronary sinus, and peripheral vein in patients undergoing primary percutaneous coronary intervention for acute STEMI and in control patients undergoing nonemergency coronary angiography or percutaneous coronary intervention for stable angina or non‐STEMI. Plasma metabolites were analyzed by targeted liquid chromatography and mass spectrometry. Metabolite levels for coronary artery, coronary sinus, and peripheral vein were compared to derive cardiac and systemic release ratios. In STEMI patients, cardiac magnetic resonance imaging was performed 2 days and 6 months after primary percutaneous coronary intervention to quantify acute myocardial edema and final infarct size, respectively. In total, 115 patients undergoing acute STEMI and 26 control patients were included. Succinate was the only metabolite significantly increased in coronary sinus blood compared with venous blood in STEMI patients, indicating cardiac release of succinate. STEMI patients had higher succinate concentrations in arterial, coronary sinus, and peripheral venous blood than patients with non‐STEMI or stable angina. Furthermore, cardiac succinate release in STEMI correlated with the extent of acute myocardial injury, quantified by cardiac magnetic resonance imaging. Conclusion Succinate release by the myocardium correlates with the extent of ischemia.

The ATI score (age-thrombus burden-index of microcirculatory resistance) determined during primary percutaneous coronary intervention predicts final infarct size in patients with ST-elevation myocardial infarction: a cardiac magnetic resonance validation study

AIMS The age-thrombus burden-index of microcirculatory resistance (ATI) score is a diagnostic tool able to predict suboptimal myocardial reperfusion before stenting, in patients with ST-elevation myocardial infarction (STEMI). We aimed to validate the ATI score against cardiac magnetic resonance imaging (cMRI). METHODS AND RESULTS The ATI score was calculated prospectively in 80 STEMI patients. cMRI was performed within 48 hours in all patients and in 50 patients at six-month follow-up to assess the extent of infarct size (IS%) and microvascular obstruction (MVO%). The ATI score was calculated using age (>50=1 point), pre-stenting index of microcirculatory resistance (IMR) (>40 and <100=1 point; ≥100=2 points) and angiographic thrombus score (4=1 point; 5=3 points). ATI score was closely related to final IS% (ATI.

The influence of coronary plaque morphology assessed by optical coherence tomography on final microvascular function after stenting in patients with ST-elevation myocardial infarction.

Objectives The index of microcirculatory resistance (IMR) provides a reproducible assessment of the status of coronary microvasculature in patients with ST-elevation myocardial infarction (STEMI). Frequency-domain optical coherence tomography (FD-OCT) enables detailed assessment of the morphology of coronary plaque. We sought to determine the influence of the initial culprit coronary plaque anatomy within the infarct-related artery on IMR after stenting in STEMI. Patients and methods In 25 STEMI patients IMR was measured immediately before and after stent implantation. FD-OCT imaging was performed at the same time points and atherothrombotic volume (ATV) before stenting, prolapsed+floating ATV after stenting and &Dgr;ATV was measured using three different strategies. Results There were no relationships between preprocedural IMR and FD-OCT parameters. Prestenting IMR was related only to pain to wire time (P: 0.02). Irrespective of the method adopted, the final IMR was related to prestenting ATV (&rgr;: 0.44, P: 0.03 for method I, &rgr;: 0.48, P: 0.02 for method II and &rgr;: 0.30, P: 0.06 for method III) and &Dgr;ATV (&rgr;: 0.41, P: 0.04 for method II and &rgr;: 0.44, P: 0.03 for method III). Conclusion IMR measured before stenting is independent of the appearances of the culprit coronary plaque within the infarct-related artery. IMR after stenting, and more importantly, the change in IMR after stenting, reflect the degree of distal embolization during stent implantation.

Index of Microcirculatory Resistance at the Time of Primary Percutaneous Coronary Intervention Predicts Early Cardiac Complications: Insights From the OxAMI (Oxford Study in Acute Myocardial Infarction) Cohort

Background Early risk stratification after primary percutaneous coronary intervention (PPCI) for ST‐segment–elevation myocardial infarction is currently challenging. Identification of a low‐risk group may improve triage of patients to alternative clinical pathways and support early hospital discharge. Our aim was to assess whether the index of microcirculatory resistance (IMR) at the time of PPCI can identify patients at low risk of early major cardiac complications and to compare its performance against guideline‐recommended risk scores. Methods and Results IMR was measured using a pressure–temperature sensor wire. Cardiac complications were defined as the composite of cardiac death, cardiogenic shock, pulmonary edema, malignant arrhythmias, cardiac rupture, and presence of left ventricular thrombus either before hospital discharge or within 30‐day follow‐up. In total, 261 patients undergoing PPCI who were eligible for coronary physiology assessment were prospectively enrolled. Twenty‐two major cardiac complications were reported. Receiver operating characteristic curve analysis confirmed the utility of IMR in predicting complications and showed significantly better performance than coronary flow reserve, the Primary Angioplasty in Myocardial Infarction II (PAMI‐II), and Zwolle score (P≤0.006). Low microvascular resistance (IMR ≤40) was measured in 159 patients (61%) of the study population and identified all patients who were free of major cardiac complications (sensitivity: 100%; 95% CI, 80.5–100%). Conclusions IMR immediately at the end of PPCI for ST‐segment–elevation myocardial infarction reliably predicts early major cardiac complications and performed significantly better than recommended risk scores. These novel data have implications for early risk stratification after PPCI.

Improved Coronary Sinus Blood Sampling for Cardiac Research

Background: Coronary sinus (CS) blood sampling is important for measuring metabolites and biomarkers in cardiovascular research, but can be technically challenging. Here we demonstrate the use of the antecubital fossa for CS blood sampling as an alternative to femoral access, and a simple technique of paired venous and CS blood gas analysis for confirmation of valid CS sampling. We also demonstrate improvement in sampling accuracy by using a coronary guide wire to stabilize the sampling catheter in the CS. Methods: Paired blood samples from CS and peripheral vein were collected from patients at the time of primary PCI for acute myocardial infarction. Venous access for CS sampling was via the antecubital vein. Blood gas analysis was used to confirm a true CS sample (pO2[CS]<pO2[v]). CS sampling was carried out with a catheter in the CS (standard technique) or with the addition of a coronary guide wire for stability (modified technique). Results: 108 patients underwent CS and peripheral venous blood sampling. The standard technique for CS sampling was used in 62 patients and the modified technique in 46 patients. Blood gas analysis confirmed a true CS sample in 77% of patients using the standard technique and 100% using the modified technique. Conclusions: CS blood sampling via the antecubital fossa is feasible and safe. Blood gas analysis of paired venous and CS samples can be used to confirm a valid CS sample. A coronary guide wire can be used to stabilise the sampling catheter in the CS, and this increases CS sampling accuracy.

22 Factors associated with poor outcome in patients taken to the catheter lab after out of hospital cardiac arrest

Introduction Out of hospital cardiac arrest (OHCA) represents a common presentation to both the emergency department and the catheter lab. Understanding of the factors associated with poor outcome in this patient group is limited; thus management decisions are challenging. The aim of this analysis was to retrospectively review clinical records for OHCA patients undergoing catheter lab procedures to determine factors associated with poor outcome. Methods Data on patients undergoing coronary angiography and percutaneous coronary intervention (PCI) between January 2009 and May 2015 at a tertiary cardiac centre were retrospectively reviewed. A keyword search was performed on all records to identify relevant procedures and these results were manually reviewed by two authors to confirm they were OHCA cases. Cases were excluded if they initially presented to a different hospital and were later transferred for investigation. Procedure details, discharge summaries, blood results and mortality data were reviewed.Abstract 22 Table 2 Selected prognostic factors associated with 30-day mortality in patients attending the catheter lab following OHCA. Values shown as n (%). For the first row, percentage is of row total, in other rows percentages is that of column total. Item Total Dead Alive P-value All Patients 242 (100.0) 42 (17.4) 200 (82.6) Cardiogenic Shock 57 (23.6) 22 (52.4) 35 (17.5) <0.001 Any PEA (n=228) 25 (11.0) 10 (25.6) 15 (7.9) 0.001 Intubated prior to catheter lab 121 (50.0) 35 (83.3) 86 (43.0) <0.001 ST-Elevation 119 (49.2) 23 (54.8) 96 (48.0) 0.426 Underwent PCI 162 (66.9) 28 (66.7) 134 (67.0) 0.967 Results 27 578 angiogram or PCI procedures were carried out between January 2009 and May 2015; 242 (0.9%) of these were patients presenting with OHCA. Forty-two patients (17.3%) died within 30 days of presentation. Demographic details of this population are shown in Table 1. Univariate analysis revealed that blood gas pH and lactate were strongly correlated with 30 day mortality (p<0.001 and p=0.002 respectively). Other factors associated with 30 day mortality included presentation with cardiogenic shock, intubation pre-hospital or in the emergency department (but not in the ?catheter lab) and the development of pulseless electrical activity (PEA) at any time (table 2). Culprit vessel (p=0.810), ST-elevation at presentation, and age were not significantly associated with 30 day mortality (p=0.426 and p=0.085 respectively). Furthermore, there was no difference in mortality between those who underwent PCI and those who received angiography alone. Conclusion OHCA constituted 0.9% of activity during the period of review. There were significant correlations between 30 day mortality and several biochemical and clinical markers available at presentation. The use of these markers may be of use in triaging patients who are likely to benefit from interventional procedures.Abstract 22 Figure 1 Flow-chart detailing patient identification for this study.Abstract 22 Table 1 Demographic details of patients attending the catheter lab following OHCA. Values shown as mean ± standard deviation or n (%). Item Number of Patients Total OHCA Patients 242 Age (Years) 62.2±13.0 Male 190 (78.5) 30 Day Mortality 42 (17.4) 1 Year Mortality 47 (19.4)Abstract 22 Figure 2 Bar charts showing blood gas pH and lactate against 30-day mortality