Cardiovascular magnetic resonance characteristics and clinical outcomes of patients with ST-elevation myocardial infarction and no standard modifiable risk factors-A DANAMI-3 substudy.

Introduction: A higher 30-day mortality has been observed in patients with first-presentation ST elevation myocardial infarction (STEMI) who have no standard modifiable cardiovascular risk factors (SMuRFs), i. e., diabetes, hypertension, hyperlipidemia, and current smoker. In this study, we evaluate the clinical outcomes and CMR imaging characteristics of patients with and without SMuRFs who presented with first-presentation STEMI. Methods: Patients from the Third DANish Study of Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction (DANAMI-3) with first-presentation STEMI were classified into those with no SMuRFs vs. those with at least one SMuRF. Results: We identified 2,046 patients; 283 (14%) SMuRFless and 1,763 (86%) had >0 SMuRF. SMuRFless patients were older (66 vs. 61 years, p < 0.001) with more males (84 vs. 74%, p < 0.001), more likely to have left anterior descending artery (LAD) as the culprit artery (50 vs. 42%, p = 0.009), and poor pre-PCI (percutaneous coronary intervention) TIMI (thrombolysis in myocardial infarction) flow ≤1 (78 vs. 64%; p < 0.001). There was no difference in all-cause mortality, non-fatal reinfarction, or hospitalization for heart failure at 30 days or at long-term follow-up. CMR imaging was performed on 726 patients. SMuRFless patients had larger acute infarct size (17 vs. 13%, p = 0.04) and a smaller myocardial salvage index (42 vs. 50%, p = 0.02). These differences were attenuated when the higher LAD predominance and/or TIMI 0-1 flow were included in the model. Conclusion: Despite no difference in 30-day mortality, SMuRFless patients had a larger infarct size and a smaller myocardial salvage index following first-presentation STEMI. This association was mediated by a larger proportion of LAD culprits and poor TIMI flow pre-PCI. Clinical trial registration: clinicaltrials.gov, unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).

Clinical Outcomes in Patients With ST-Segment Elevation MI and No Standard Modifiable Cardiovascular Risk Factors.

BACKGROUND: The author recently reported ∼50% excess early mortality in patients with first-presentation ST-segment elevation myocardial infarction (STEMI) without standard modifiable cardiovascular risk factors (SMuRFs); the cause of this is not clear. OBJECTIVES: The aim of this study was to examine differences in infarct characteristics and clinical outcomes in patients with versus without SMuRFs (dyslipidemia, hypertension, diabetes mellitus, and smoking). METHODS: Individual-level data were pooled from 10 randomized percutaneous intervention (PCI) trials in which infarct size was measured within 1 month by either cardiac magnetic resonance or technetium-99m sestamibi single-photon emission computed tomography imaging. First-presentation STEMI was classified into 2 groups according to the presence or absence of at least 1 SMuRF. RESULTS: Among 2,862 patients, 524 (18.3%) were SMuRF-less. After adjusting for study effect, SMuRF-less patients had more frequent poor pre-PCI flow Thrombolysis In Myocardial Infarction 0/1 compared with patients with at least 1 SMuRF (72.0% vs 64.1%; OR: 1.35; 95% CI: 1.08-1.70). There were no independent associations between the presence or absence of SMuRFs at baseline and infarct size (estimate = -0.35; 95% CI: -1.93 to 1.23), left ventricular ejection fraction (estimate = -0.06; 95% CI: -1.33 to 1.20), or mortality at 30 days (HR: 0.46; 95% CI: 0.19-1.07) and 1 year (HR: 0.74; 95% CI: 0.43-1.29). CONCLUSIONS: First-presentation STEMI patients with no identifiable baseline SMuRFs had a higher risk of Thrombolysis In Myocardial Infarction flow grade 0/1 pre-PCI. However, after adjustment, there were no significant associations between SMuRF-less status and infarct size, left ventricle ejection fraction, or mortality.

Progression of coronary atherosclerosis in patients without standard modifiable risk factors.

BACKGROUND AND AIMS: The outcome of patients with clinical coronary artery disease despite traditional risk factors is poorly understood. METHODS: Clinical characteristics and plaque burden on serial intravascular ultrasonography were compared in patients without (n â€‹= â€‹165) and with (n â€‹= â€‹492) standard modifiable risk factors after matching on age, sex and use of statins from a database of 5823 patients participating in clinical trials of anti-atherosclerotic therapies. RESULTS: Patients without standard modifiable risk factors had lower baseline systolic blood pressure (118 â€‹± â€‹12 vs. 129 â€‹± â€‹17 â€‹mmHg, p â€‹< â€‹0.001), low-density lipoprotein cholesterol (87 â€‹± â€‹21 vs. 104 â€‹± â€‹34 â€‹mg/dl, p â€‹< â€‹0.001), triglycerides [106 vs. 136 â€‹mg/dl, p â€‹< â€‹0.001)] and C-reactive protein [1.5 vs. 2.1 â€‹mg/l, p â€‹= â€‹0.001]. At baseline, patients without modifiable risk factors had a lower percent atheroma volume (35.7 â€‹± â€‹8.6 vs. 38 â€‹± â€‹8.8%, p â€‹= â€‹0.004) and total atheroma volume (174.7 â€‹± â€‹80 vs. 190.9 â€‹± â€‹84 â€‹mm3, p â€‹= â€‹0.03) and less images with calcification (22.2 vs. 26.5%, p â€‹= â€‹0.025). The use of aspirin and statin prior to and during the trials was similar. The use of ACE inhibitors and beta blockers was lower in the no risk factor group prior to and during the trials. The change in percent atheroma volume (-0.2 â€‹± â€‹2.8 vs. -0.1 â€‹± â€‹3.6%, p â€‹= â€‹0.71), total atheroma volume (-5.5 â€‹± â€‹23.4 vs. -3.8 â€‹± â€‹22.7 â€‹mm3, p â€‹= â€‹0.42), and the percentage of patients demonstrating any degree of progression (50.9% vs 45.1%, p â€‹= â€‹0.20) were similar in those without and with standard modifiable risk factors, respectively. CONCLUSION: Patients who develop clinical coronary atherosclerosis without standard modifiable risk factors have similar rates of plaque progression to those with traditional risk factors.

Troponin-positive chest pain with unobstructed coronary arteries: incremental diagnostic value of cardiovascular magnetic resonance imaging.

AIMS: Troponin-positive chest pain patients with unobstructed coronaries represent a clinical dilemma. Cardiovascular magnetic resonance (CMR) imaging has an increasingly prominent role in the assessment of these patients; however, its utility in addition to expert clinical judgement is unclear. We sought to determine the incremental diagnostic value of CMR and the heterogeneity in diagnoses by experienced cardiologists when presented with blinded clinical and investigative data in this population. METHODS AND RESULTS: A total of 125 consecutive patients presenting to a tertiary centre between 2010 and 2014 with cardiac chest pain, elevated troponin (>29 ng/L), and unobstructed coronaries were enrolled and underwent CMR. A panel of three experienced cardiologists unaware of the CMR diagnosis and blinded to each other's assessment provided a diagnosis based on clinical and investigative findings. A consensus panel diagnosis was defined as two or more cardiologists sharing the same clinical diagnosis. Findings were classified into acute myocarditis, Takotsubo cardiomyopathy, acute myocardial infarction (AMI), or indeterminate. CMR provided a diagnosis in 87% of patients. Consensus panel diagnosis and CMR were concordant in 65/125 (52%) patients. There was an only moderate level of agreement between the three cardiologists (k = 0.47, P < 0.05) and a poor level of agreement between the consensus panel and CMR (k = 0.38, P < 0.05) with the most disagreement seen in patients with AMI diagnosed on CMR. CONCLUSION: The clinical diagnosis of patients with non-obstructive coronaries and positive troponin remains a challenge. The concordance between CMR and clinical diagnosis is poor. CMR provides a diagnosis in majority of these patients.

Predictors and outcome of no-reflow post primary percutaneous coronary intervention for ST elevation myocardial infarction.

BACKGROUND: No-reflow (TIMI < 3) during primary PCI (PCI) for STEMI occurs in 11-41% of cases, indicates poor myocardial tissue perfusion, and is associated with a poor outcome. We aimed to determine predictors and 12 month outcomes of patients who developed no-reflow. METHODS: We analysed the PCI database of The Canberra Hospital and identified 781 patients who underwent primary PCI during 2008-2012. Follow-up at 12 months was with letter, phone call and review of hospital records. RESULTS: No-reflow was observed in 189 patients (25%) at the end of the procedure. Patients with no-reflow were older (64 vs. 61 years, p = 0.03). No-reflow patients were more likely to have initial TIMI flow < 3 (89% vs. 79%, p = 0.001), thrombus score ≥ 4 (83% vs. 69%, p = 0.0001), higher use of glycoprotein IIb/IIIa inhibitors (57% vs. 48%, p = 0.03) and longer median symptom to balloon time (223 min vs. 192 min, p = 0.004). No-reflow was an independent predictor of mortality (HR 1.95, CI 1.04-3.59, p = 0.037) during 12 month follow-up. On multivariate analysis, age > 60 years, thrombus score ≥ 4 and symptom to balloon time > 360 min were independent predictors of no-reflow. In 17% of cases of no reflow, it occurred only after stent insertion. CONCLUSIONS: No-reflow occurred in 25% of STEMI patients undergoing primary PCI and was more likely with older age, high thrombus burden and delayed presentation. No-reflow was associated with a higher risk of death at 12 month follow-up.

The effect of coronary artery plaque composition, morphology and burden on Absorb bioresorbable vascular scaffold expansion and eccentricity - A detailed analysis with optical coherence tomography.

AIMS: Suboptimal stent expansion correlates with adverse cardiac events. There is limited information regarding Absorb bioresorbable vascular scaffold (BVS) expansion characteristics. Optical coherence tomography (OCT) allows for high-resolution assessment of plaque morphology, composition and assessment of BVS expansion. This study evaluates coronary plaque composition, morphology and burden and their effect on Absorb BVS expansion using OCT. METHODS AND RESULTS: Two thousand three hundred and thirty four frames totalling 462.6 mm of BVS from twenty OCT-guided BVS implantations were examined. 200 µm longitudinal cross-sections of each BVS were analysed for lumen contours and plaque characteristics. The relationship between each plaque characteristic and scaffold expansion index (SEI) or scaffold eccentricity index (SEC) was analysed by repeated measures ANOVA. Forty-four fibrous and 265 calcific plaques were identified. Lower SEI was significantly (p<0.001) associated with greater calcific plaque (CP) area (mean SEI 78.9% vs. 80.0%), thickness (78.5% vs. 80.4%) and lower CP depth (78.3% vs. 80.2%). Lower SEC was significantly (p<0.001) associated with greater fibrous plaque (FP) area (0.84 vs. 0.85), thickness (0.83 vs. 0.86), arc angle (0.84 vs. 0.85), greater CP area (0.83 vs. 0.86), CP thickness (0.83 vs. 0.86), CP angle (0.84 vs. 0.85) and lower CP depth (0.84 vs. 0.85). Greater FP area was associated with greater SEI (81.0% vs. 80.0%, p<0.001), even after adjustment for target vessel size. Greater FP angle (80.7% vs 78.3%, p<0.001) and quadrants occupied were also associated (80.0% vs 78.5%, p<0.002) with greater SEI. CONCLUSION: BVS expansion and eccentricity are significantly impacted by plaque composition, morphology and burden.

Automated quantification of myocardial salvage in a rat model of ischemia-reperfusion injury using 3D high-resolution magnetic resonance imaging (MRI).

BACKGROUND: Quantification of myocardial "area at risk" (AAR) and myocardial infarction (MI) zone is critical for assessing novel therapies targeting myocardial ischemia-reperfusion (IR) injury. Current "gold-standard" methods perfuse the heart with Evan's Blue and stain with triphenyl tetrazolium chloride (TTC), requiring manual slicing and analysis. We aimed to develop and validate a high-resolution 3-dimensional (3D) magnetic resonance imaging (MRI) method for quantifying MI and AAR. METHODS AND RESULTS: Forty-eight hours after IR was induced, rats were anesthetized and gadopentetate dimeglumine was administered intravenously. After 10 minutes, the coronary artery was re-ligated and a solution containing iron oxide microparticles and Evan's Blue was infused (for comparison). Hearts were harvested and transversally sectioned for TTC staining. Ex vivo MR images of slices were acquired on a 9.4-T magnet. T2* data allowed visualization of AAR, with microparticle-associated signal loss in perfused regions. T1 data demonstrated gadolinium retention in infarcted zones. Close correlation (r=0.92 to 0.94; P<0.05) of MRI and Evan's Blue/TTC measures for both AAR and MI was observed when the combined techniques were applied to the same heart slice. However, 3D MRI acquisition and analysis of whole heart reduced intra-observer variability compared to assessment of isolated slices, and allowed automated segmentation and analysis, thus reducing interobserver variation. Anatomical resolution of 81 µm(3) was achieved (versus ≈2 mm with manual slicing). CONCLUSIONS: This novel, yet simple, MRI technique allows precise assessment of infarct and AAR zones. It removes the need for tissue slicing and provides opportunity for 3D digital analysis at high anatomical resolution in a streamlined manner accessible for all laboratories already performing IR experiments.

Selective inhibition of the master regulator transcription factor Egr-1 with catalytic oligonucleotides reduces myocardial injury and improves left ventricular systolic function in a preclinical model of myocardial infarction.

BACKGROUND: Egr-1 is implicated in the pathogenesis of myocardial ischemia-reperfusion injury. The aim of this study was to ascertain the effectiveness of intracoronary delivery of DNAzyme targeting the transcription factor Egr-1 at reperfusion following experimental myocardial ischemia. METHODS AND RESULTS: Functional DNAzyme targeting Egr-1 or a size-matched scrambled control were delivered via the intracoronary route immediately on reperfusion after 60 minutes' balloon occlusion of the left anterior descending coronary artery in a pig model of myocardial I/R injury (n=7 per treatment group). Heart function and extent of myocardial infarction were determined following intervention by echocardiography and cardiac magnetic resonance imaging, respectively. Hearts were removed and examined for molecular and histological markers of inflammation and apoptosis. Administration of functional DNAzyme led to an overall decrease in the expression of inflammatory markers including intracellular adhesion molecule-1, tissue factor, and complement 3, with associated decreases in the extent of neutrophil infiltration, oxidative damage, and subsequent apoptosis within the infarct border zone. Functional significance was indicated by an increase in salvaged left ventricular myocardium (P=0.012), ejection fraction (P=0.002), and fractional area change (P=0.039) in the functional DNAzyme-treated group compared with the control. CONCLUSIONS: Egr-1 silencing through intracoronary delivery of a targeting DNAzyme at the time of reperfusion following acute myocardial ischemia decreases myocardial inflammation and apoptosis leading to improved cardiac function.

Cardiac magnetic resonance imaging of rapid VCAM-1 up-regulation in myocardial ischemia-reperfusion injury.

Inflammatory response plays an important role in myocardial ischaemia-reperfusion (IR) injury. Up-regulation of vascular cell adhesion molecule-1 (VCAM) contributes to this. We examined the feasibility of using intravenously administered VCAM-MPIO (microparticle iron oxide) to characterize VCAM expression patterns in myocardial IR injury. Myocardial ischemia was simulated by 30 min of transient ligation of the left coronary vessel in rats. Purified, monoclonal, rat-specific, mouse VCAM antibody coupled to MPIO was administered through the tail vein at 3 h post reperfusion and the rats were sacrificed 1 h later. High resolution 3D ex vivo MRI images were acquired at 9.4 Tesla. Extensive foci of signal voids were observed on T2*-weighted gradient-echo sequences, which corresponded to focal deposits of MPIOs observed in histological sections. The spatial density of the signal voids (expressed as a percentage of pixels below a threshold value) was increased in the peri-infarct zone compared with non-infarct zone (32.5 ± 4% vs. 13.9 ± 5%; n = 6; p < 0.05) and was substantially greater than the signal loss due to non-specific binding seen in rats administered IgG control MPIO (2.0 ± 1%; n = 6; p < 0.05). The VCAM-specific MPIO signal was also seen in myocardium and pericardium in segments remote from the IR injury, but not in rats undergoing a sham operation. In conclusion, molecular imaging in a model of myocardial IR injury is possible using high field MRI and VCAM-MPIOs and may provide novel insights beyond those achieved by standard histological and molecular analysis.