Matthew M.Y. Lee

Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS–NSTEMI randomized trial

Aim We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care. Methods and results We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (−0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups. Conclusion In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness.

Reducing Personal Exposure to Particulate Air Pollution Improves Cardiovascular Health in Patients with Coronary Heart Disease

Background: Air pollution exposure increases cardiovascular morbidity and mortality and is a major global public health concern. Objectives: We investigated the benefits of reducing personal exposure to urban air pollution in patients with coronary heart disease. Methods: In an open randomized crossover trial, 98 patients with coronary heart disease walked on a predefined route in central Beijing, China, under different conditions: once while using a highly efficient face mask, and once while not using the mask. Symptoms, exercise, personal air pollution exposure, blood pressure, heart rate, and 12-lead electrocardiography were monitored throughout the 24-hr study period. Results: Ambient air pollutants were dominated by fine and ultrafine particulate matter (PM) that was present at high levels [74 μg/m3 for PM2.5 (PM with aerodynamic diamater <2.5 µm)]. Consistent with traffic-derived sources, this PM contained organic carbon and polycyclic aromatic hydrocarbons and was highly oxidizing, generating large amounts of free radicals. The face mask was well tolerated, and its use was associated with decreased self-reported symptoms and reduced maximal ST segment depression (–142 vs. –156 μV, p = 0.046) over the 24-hr period. When the face mask was used during the prescribed walk, mean arterial pressure was lower (93 ± 10 vs. 96 ± 10 mmHg, p = 0.025) and heart rate variability increased (high-frequency power: 54 vs. 40 msec2, p = 0.005; high-frequency normalized power: 23.5 vs. 20.5 msec, p = 0.001; root mean square successive differences: 16.7 vs. 14.8 msec, p = 0.007). However, mask use did not appear to influence heart rate or energy expenditure. Conclusions: Reducing personal exposure to air pollution using a highly efficient face mask appeared to reduce symptoms and improve a range of cardiovascular health measures in patients with coronary heart disease. Such interventions to reduce personal exposure to PM air pollution have the potential to reduce the incidence of cardiovascular events in this highly susceptible population.

Adenosine : Physiology, Pharmacology, and Clinical Applications

Adenosine is a ubiquitous extracellular signaling molecule with essential functions in human physiology. Due to the widespread expression of adenosine receptors, it has far-reaching effects across many different organ systems. With a prominent role in the cardiovascular system, it has been extensively studied for both its therapeutic and diagnostic abilities. One of the key areas of use is in the coronary circulation whereby adenosine produces a hyperemic response. An important target of adenosine is the coronary microcirculation whereby adenosine acts as a prominent vasodilator with many of the beneficial effects of adenosine reflected in its capacity to affect the microvessels. Adenosine also has an important role in the pre-conditioned state and also in the attenuation of ischemia-reperfusion injury. This review examines the physiology, pharmacology, and therapeutic applications of adenosine in the human cardiovascular system and provides a brief overview of important aspects of the adenosine-cardiac interaction. It also examines the role of adenosine in the coronary hyperemic response and discusses the use of adenosine for this purpose. After recent concerns about the use of adenosine, a discussion regarding safety of this drug is provided. A brief review of novel agents used to initiate coronary hyperemia is also provided.

Assessment of Fractional Flow Reserve in Patients With Recent Non–ST-Segment–Elevation Myocardial Infarction Comparative Study With 3-T Stress Perfusion Cardiac Magnetic Resonance Imaging

Background—The use of fractional flow reserve (FFR) in acute coronary syndromes is controversial. The British Heart Foundation Fractional Flow Reserve Versus Angiography in Guiding Management to Optimize Outcomes in Non-ST-Elevation Myocardial Infarction (FAMOUS-NSTEMI) study (NCT01764334) has recently demonstrated the safety and feasibility of FFR measurement in patients with non–ST-segment–elevation myocardial infarction. We report the findings of the cardiac magnetic resonance (CMR) substudy to assess the diagnostic accuracy of FFR compared with 3.0-T stress CMR perfusion. Methods and Results—One hundred six patients with non–ST-segment–elevation myocardial infarction who had been referred for early invasive management were included from 2 centers. FFR was measured in all major patent epicardial coronary arteries with a visual stenosis estimated at ≥30%, and if percutaneous coronary intervention was performed, an FFR assessment was repeated. Myocardial perfusion was assessed with stress perfusion CMR at 3 T. The mean age was 56.7±9.8 years; 82.6% were men. Mean time from FFR evaluation to CMR was 6.1±3.1 days. The mean±SD left ventricular ejection fraction was 58.2±9.1%. Mean infarct size was 5.4±7.1%, and mean troponin concentration was 5.2±9.2 &mgr;g/L. There were 34 fixed and 160 inducible perfusion defects. There was a negative correlation between the number of segments with a perfusion abnormality and FFR (r=−0.77; P<0.0001). The overall sensitivity, specificity, positive predictive value, and negative predictive value for an FFR of ⩽0.8 were 91.4%, 92.2%, 76%, and 97%, respectively. Diagnostic accuracy was 92%. The positive and negative predictive values of FFR for flow-limiting coronary artery disease (FFR⩽0.8) in patients with non–ST-segment–elevation myocardial infarction (n=21) who underwent perfusion CMR before invasive angiography were 92% and 93%, respectively. Receiver operating characteristic analysis indicated that the optimal cutoff value of FFR for demonstrating reversible ischemia on CMR was ⩽0.805 (area under the receiver operating characteristic curve, 0.94 [0.9–0.99]; P<0.0001). Conclusions—FFR in patients with recent non–ST-segment–elevation myocardial infarction showed high concordance with myocardial perfusion in matched territories as revealed by 3.0-T stress perfusion CMR. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02073422.

Diagnostic accuracy of 3.0-T magnetic resonance T1 and T2 mapping and T2-weighted dark-blood imaging for the infarct-related coronary artery in Non-ST-segment elevation myocardial infarction

Background Patients with recent non–ST‐segment elevation myocardial infarction commonly have heterogeneous characteristics that may be challenging to assess clinically. Methods and Results We prospectively studied the diagnostic accuracy of 2 novel (T1, T2 mapping) and 1 established (T2‐weighted short tau inversion recovery [T2W‐STIR]) magnetic resonance imaging methods for imaging the ischemic area at risk and myocardial salvage in 73 patients with non–ST‐segment elevation myocardial infarction (mean age 57±10 years, 78% male) at 3.0‐T magnetic resonance imaging within 6.5±3.5 days of invasive management. The infarct‐related territory was identified independently using a combination of angiographic, ECG, and clinical findings. The presence and extent of infarction was assessed with late gadolinium enhancement imaging (gadobutrol, 0.1 mmol/kg). The extent of acutely injured myocardium was independently assessed with native T1, T2, and T2W‐STIR methods. The mean infarct size was 5.9±8.0% of left ventricular mass. The infarct zone T1 and T2 times were 1323±68 and 57±5 ms, respectively. The diagnostic accuracies of T1 and T2 mapping for identification of the infarct‐related artery were similar (P=0.125), and both were superior to T2W‐STIR (P<0.001). The extent of myocardial injury (percentage of left ventricular volume) estimated with T1 (15.8±10.6%) and T2 maps (16.0±11.8%) was similar (P=0.838) and moderately well correlated (r=0.82, P<0.001). Mean extent of acute injury estimated with T2W‐STIR (7.8±11.6%) was lower than that estimated with T1 (P<0.001) or T2 maps (P<0.001). Conclusions In patients with non–ST‐segment elevation myocardial infarction, T1 and T2 magnetic resonance imaging mapping have higher diagnostic performance than T2W‐STIR for identifying the infarct‐related artery. Compared with conventional STIR, T1 and T2 maps have superior value to inform diagnosis and revascularization planning in non–ST‐segment elevation myocardial infarction. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02073422.

Thrombus aspiration during myocardial infarction.

To the Editor: In the Thrombus Aspiration in ST-Segment Elevation Myocardial Infarction (STEMI) in Scandinavia (TASTE) trial, Frobert et al. (Oct. 24 issue)1 report that routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI), as compared with PCI alone, did not reduce 30-day mortality in the study patients. Aspiration thrombectomy during primary PCI is recommended to reduce the coronary thrombus burden in clinical practice.2 Accordingly, we call into question the TASTE trial design. First, given the open inclusion criteria, many patients who had no or minimal evidence of thrombus on initial angiography of the target (or culprit) vessel would have been included in the study. In such circumstances, aspiration thrombectomy may have no value and may cause harm (e.g., vessel dissection). Second, balloon angioplasty may cause clot embolization and microvascular obstruction and thus limit the benefit of concomitant aspiration thrombectomy. In the TASTE trial,3 the use of balloon angioplasty before or after thrombectomy or the use of direct stenting was not described. Third, the sample size was based on the rates of cardiac death at 30 days in the Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS).4 However, the primary outcome in the TASTE study was all-cause mortality at 30 days, which raises the question of whether the study was underpowered for its primary outcome. Given these reservations, we are very concerned that the negative results of this study may militate against the appropriate use of thrombectomy in high-risk patients with STEMI.

79 Diagnostic Accuracy of Myocardial Fractional Flow Reserve for Reversible Perfusion Abnormalities in Patients with Recent Non-ST Elevation Myocardial Infarction

Background Myocardial fractional flow reserve (FFR) has uncertain validity in patients with recent myocardial infarction and the use of FFR in this setting is controversial. We performed a prospective study to assess the diagnostic accuracy of FFR in patients with a recent non-ST segment myocardial infarction (NSTEMI). Methods NSTEMI patients who had been referred for early invasive management were included. FFR was measured in all major patent epicardial coronary arteries with a visual stenosis estimated at ≥30% severity. Where clinically appropriate, an FFR assessment following PCI was also performed. Patients were scheduled for a stress perfusion 3T MRI following discharge from hospital.In a subsetof patients MRI was performed prior to coronary angiography/PCI. Baseline stress (I.V. adenosine 140 µg/kg/min) and rest perfusion MRI images were analysed side-by-side using dedicated software (Argus Dynamic Signal, Siemens, Erlangen, Germany). The stress and rest perfusion scans were viewed simultaneously, areas of hypoperfusion were assigned to coronary territories using the American Heart Association coronary arterial segment model. The analyses were performed independently by two observers who were blinded to the FFR results. In each patient, the coronary artery territories with abnormal perfusion were recorded. In cases of disagreement between observers, a third blinded observer adjudicated. Results 106 NSTEMI patients (mean age 56.7 ± 9.8 years, 82.6% male) were included. The mean time between the FFR evaluation and MRI was 5.8 ± 3.1 days. The mean ± SD left ventricular ejection fraction was 58.2 ± 9.1%. Mean infarct size was 5.4 ± 7.1% and mean troponin was 5.2 ± 9.2 g/L. A total of 1696 segments were available for analysis. 34 segments were excluded from the analysis due to problematic image quality so 1664 segments were finally included.Of these, 824 segments were available for comparison with FFR. 156 coronary arteries were assessed 92 in the infarct-related arteries and 64 in the non-infarct-related arteries. Of these, 28(17.1%) and 33(21.1%) arteries had an FFR ≤ 0.75 and ≤0.80, respectively. There was a negative correlation between the number of ischaemic segments and FFR (r = -0.79, 0 < 0.0001).The sensitivity, specificity, PPV and NPV for FFR ≤ 0.8 was 91.17%, 95.7%, 91.2% and 95.7% respectively. ROC analysis defined the optimal FFR cut off value for identification of reversible ischaemia on MRI to be ≤0.8 (AUC 0.94 (0.89–0.99), p < 0.0001). An FFR ≤ 0.8 was associated with a sensitivity of 88.6% and a specificity of 94%. Conclusion FFR measured in patients with recent NSTEMI has a high level of accuracy for inducible perfusion abnormalities revealed by 3T stress MRI, a non-invasive reference method.

Microvascular complications in diabetes patients with heart failure and reduced ejection fraction-insights from the Beta-blocker Evaluation of Survival Trial

The role of microvascular complications in the risk conferred by diabetes in heart failure with reduced ejection fraction (HFrEF) is unknown.

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov).