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Relation between high levels of myeloperoxidase in the culprit artery and microvascular obstruction, infarct size and reverse remodeling in ST-elevation myocardial infarction.

ABSTRACT: To better understand the role of myeloperoxidases (MPO) in microvascular obstruction (MO) phenomenon and infarct size (IS) using cardiac magnetic resonance (CMR) data in patients with acute myocardial infarction (AMI).40 consecutive patients classified according to the median level of MPO in the culprit artery. A CMR study was performed during the week following AMI and at 6 months, with late gadolinium enhancement sequences.Persistent MO was observed in the same proportion (50 vs. 65%, p = 0.728) between the low vs. high MPO group levels. However, the extent of the microvascular obstruction was significantly greater in the high-MPO group (6 (0-9) vs.16.5 (0-31), p = 0.027), together with a greater infarct size, and a trend towards a lower left ventricular ejection fraction (LVEF) (p = 0.054) at one week. CMR data at 6 months showed that reverse systolic remodeling was two fold more present in the low-MPO group (p = 0.058). Interestingly, the extent of MO (8.5 (6.5-31) vs. 4.1 (3-11.55), p = 0.042) and IS remained significantly greater (24.5 (9.75-35) vs. 7.5 (2.5-18.75), p = 0.022) in the high-MPO group. Moreover, MPO in the culprit artery appeared to correlate positively with MPO in non-culprit arteries and serum, and with troponin levels and peak CK.This patient-based study revealed in patients after AMI that high MPO levels in the culprit artery were associated with more severe microvascular obstruction and greater IS. These findings may provide new insights pathophysiology explanation for the adverse prognostic impact of MO.

SUBMITTER: Stamboul K

PROVIDER: S-EPMC5509133 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:BackgroundFailed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors.MethodsIMR (n = 288) and CFR (n = 283; mean age [SD], 60 [12] years) were measured acutely using guide wire-based thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death or first heart failure hospitalization was independently adjudicated (median follow-up 845 days).ResultsMyocardial hemorrhage and microvascular obstruction occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and CFR were associated with microvascular pathology (none vs. microvascular obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median [interquartile range], IMR: 17 [12.0-33.0] vs. 17 [13.0-39.0] vs. 37 [21.0-63.0], P < 0.001; CFR: 1.7 [1.4-2.5] vs. 1.5 [1.1-1.8] vs. 1.4 [1.0-1.8], P < 0.001), whereas thrombolysis in myocardial infarction blush grade was not. IMR was a multivariable associate of changes in left ventricular end-diastolic volume (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09 [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for these outcomes as <50% ST-segment resolution on the ECG.ConclusionsIMR is more closely associated with microvascular pathology, left ventricular remodeling, and health outcomes than the angiogram or CFR.Trial registrationNCT02072850.FundingA British Heart Foundation Project Grant (PG/11/2/28474), the National Health Service, the Chief Scientist Office, a Scottish Funding Council Senior Fellowship, a British Heart Foundation Intermediate Fellowship (FS/12/62/29889), and a nonfinancial research agreement with Siemens Healthcare.

Project description:Background Despite optimized medical management and techniques of primary percutaneous coronary intervention, a substantial proportion of patients with ST-segment-elevation myocardial infarction (STEMI) display significant microvascular damage. Thrombotic microvascular obstruction (MVO) has been implicated in the pathogenesis of microvascular and subsequent myocardial damage attributed to distal embolization and microvascular platelet plugging. However, there are only scarce data regarding the effect of platelet reactivity on MVO. Methods and Results We prospectively evaluated 105 patients in 2 distinct periods (2012-2013 and 2016-2018) who presented with first ST-segment-elevation myocardial infarction and underwent primary percutaneous coronary intervention. All patients were treated with dual antiplatelet therapy (DAPT). Blood samples were analyzed for platelet reactivity, and cardiac magnetic resonance imaging scans were evaluated for late gadolinium enhancement and MVO. DAPT suboptimal response was defined as hyporesponsiveness to either aspirin or P2Y12 receptor inhibitor agents and demonstrated in 31 patients (29.5%) of the current cohort. Suboptimal platelet response to DAPT was associated with a significantly greater extent of MVO when expressed as a percentage of the left ventricular mass, left ventricular scar, and the number of myocardial left ventricular segments showing MVO (P<0.01 for each). Adjusted multivariable logistic regression model revealed that suboptimal response to DAPT is significantly associated with both greater late gadolinium enhancement (P<0.01) and MVO extent (odds ratio, 3.7 [95% CI, 1.3-10.5]; P=0.01). Patients with a greater extent of MVO were more likely to sustain major adverse cardiovascular events at a 1-year follow-up (37% versus 11%; P<0.01). Conclusions In patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, platelet reactivity in response to DAPT is a key predictor of the extent of both myocardial and microvascular damage.

Project description:Background Invasive measures of microvascular resistance in the culprit coronary artery have potential for risk stratification in acute ST-segment-elevation myocardial infarction. We aimed to investigate the pathological and prognostic significance of coronary thermodilution waveforms using a diagnostic guidewire. Methods and Results Coronary thermodilution was measured at the end of percutaneous coronary intervention, (PCI) and contrast-enhanced cardiac magnetic resonance imaging (MRI) was intended on day 2 and 6 months later to assess left ventricular (LV) function and pathology. All-cause death or first heart failure hospitalization was a pre-specified outcome (median follow-up duration 1469 days). Thermodilution recordings underwent core laboratory assessment. A total of 278 patients with acute ST-segment elevation myocardial infarction EMI (72% male, 59±11 years) had coronary thermodilution measurements classified as narrow unimodal (n=143 [51%]), wide unimodal (n=100 [36%]), or bimodal (n=35 [13%]). Microvascular obstruction and myocardial hemorrhage were associated with the thermodilution waveform pattern ( P=0.007 and 0.011, respectively), and both pathologies were more prevalent in patients with a bimodal morphology. On multivariate analysis with baseline characteristics, thermodilution waveform status was a multivariable associate of microvascular obstruction (odds ratio [95% confidence interval]=5.29 [1.73, 16.22];, P=0.004) and myocardial hemorrhage (3.45 [1.16, 10.26]; P=0.026), but the relationship was not significant when index of microvascular resistance (IMR) >40 or change in index of microvascular resistance (5 per unit) was included. However, a bimodal thermodilution waveform was independently associated with all-cause death and hospitalization for heart failure (odds ratio [95% confidence interval]=2.70 [1.10, 6.63]; P=0.031), independent of index of microvascular resistance>40, ST-segment resolution, and TIMI (Thrombolysis in Myocardial Infarction) Myocardial Perfusion Grade. Conclusions The thermodilution waveform in the culprit coronary artery is a biomarker of prognosis and may be useful for risk stratification immediately after reperfusion therapy.

Project description:BackgroundThe success of coronary reperfusion therapy in ST-segment-elevation myocardial infarction (MI) is commonly limited by failure to restore microvascular perfusion.Methods and resultsWe performed a prospective cohort study in patients with reperfused ST-segment-elevation MI who underwent cardiac magnetic resonance 2 days (n=286) and 6 months (n=228) post MI. A serial imaging time-course study was also performed (n=30 participants; 4 cardiac magnetic resonance scans): 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value of <20 ms. Microvascular obstruction was assessed with late gadolinium enhancement. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥20% at 6 months. Cardiovascular death or heart failure events post discharge were assessed during follow-up. Two hundred forty-five patients had evaluable T2* data (mean±age, 58 [11] years; 76% men). Myocardial hemorrhage 2 days post MI was associated with clinical characteristics indicative of MI severity and inflammation. Myocardial hemorrhage was a multivariable associate of adverse remodeling (odds ratio [95% confidence interval]: 2.64 [1.07-6.49]; P=0.035). Ten (4%) patients had a cardiovascular cause of death or experienced a heart failure event post discharge, and myocardial hemorrhage, but not microvascular obstruction, was associated with this composite adverse outcome (hazard ratio, 5.89; 95% confidence interval, 1.25-27.74; P=0.025), including after adjustment for baseline left ventricular end-diastolic volume. In the serial imaging time-course study, myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. The amount of hemorrhage (median [interquartile range], 7.0 [4.9-7.5]; % left ventricular mass) peaked on day 2 (P<0.001), whereas microvascular obstruction decreased with time post reperfusion.ConclusionsMyocardial hemorrhage and microvascular obstruction follow distinct time courses post ST-segment-elevation MI. Myocardial hemorrhage was more closely associated with adverse outcomes than microvascular obstruction.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850.

Project description:ObjectivesThis study sought to determine the incidence and prognostic significance of persistent iron in patients post-ST-segment elevation myocardial infarction (STEMI).BackgroundThe clinical significance of persistent iron within the infarct core after STEMI complicated by acute myocardial hemorrhage is poorly understood.MethodsPatients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction]). Cardiac magnetic resonance imaging including T2* (observed time constant for the decay of transverse magnetization seen with gradient-echo sequences) mapping was performed at 2 days and 6 months post-STEMI. Myocardial hemorrhage or iron was defined as a hypointense infarct core with T2* signal <20 ms.ResultsA total of 203 patients (age 57 ± 11 years, n = 158 [78%] male) had evaluable T2* maps at 2 days and 6 months post-STEMI; 74 (36%) patients had myocardial hemorrhage at baseline, and 44 (59%) of these patients had persistent iron at 6 months. Clinical associates of persistent iron included heart rate (p = 0.009), the absence of a history of hypertension (p = 0.017), and infarct size (p = 0.028). The presence of persistent iron was associated with worsening left ventricular (LV) end-diastolic volume (regression coefficient: 21.10; 95% confidence interval [CI]: 10.92 to 31.27; p < 0.001) and worsening LV ejection fraction (regression coefficient: -6.47; 95% CI: -9.22 to -3.72; p < 0.001). Persistent iron was associated with the subsequent occurrence of all-cause death or heart failure (hazard ratio: 3.91; 95% CI: 1.37 to 11.14; p = 0.011) and major adverse cardiac events (hazard ratio: 3.24; 95% CI: 1.09 to 9.64; p = 0.035) (median follow-up duration 1,457 days [range 233 to 1,734 days]).ConclusionsPersistent iron at 6 months post-STEMI is associated with worse LV and longer-term health outcomes. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).

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Relation between high levels of myeloperoxidase in the culprit artery and microvascular obstruction, infarct size and reverse remodeling in ST-elevation myocardial infarction.

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