Instantaneous unmasking of myocardial hibernation induced by microvascular obstruction.
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ABSTRACT:
SUBMITTER: Bhagwat AR
PROVIDER: S-EPMC5067766 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
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Instantaneous unmasking of myocardial hibernation induced by microvascular obstruction.
Bhagwat Ajit R AR Mukhedkar Sachin M SM
Indian heart journal 20160201
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Project description:Microvascular obstruction (MVO) is a recognised phenomenon following mechanical reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI). Invasive and non-invasive modalities to detect and measure the extent of MVO vary in their accuracy, suggesting that this phenomenon may reflect a spectrum of pathophysiological changes at the level of coronary microcirculation. The importance of detecting MVO lies in the observation that its presence adds incremental risk to patients following STEMI treatment. This increased risk is associated with adverse cardiac remodelling seen on cardiac imaging, increased infarct size, and worse patient outcomes. This review provides an outline of the pathophysiology, clinical implications, and prognosis of MVO in STEMI. It describes historic and novel pharmacological and non-pharmacological therapies to address this phenomenon in conjunction with primary PCI.
| S-EPMC10532390 | biostudies-literature
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.
| S-EPMC4718183 | biostudies-literature
Project description:IntroductionMyocardial hemorrhage (IMH) and persistent microvascular obstruction (MVO) are associated with impaired myocardial recovery and adverse clinical outcomes in STEMI patients. However, their relationship with circulating inflammatory biomarkers is unclear in human patients.Methods and resultsTwenty consecutive patients referred for primary percutaneous coronary intervention of first STEMI were included in a prospective study. Blood sampling was performed at admission, 4, 12, 24, 48 hours, 7 and 30 days after reperfusion for inflammatory biomarker (C reactive protein, fibrinogen, interleukin-6 (IL-6) and neutrophils count) assessment. At seven days, cardiovascular magnetic resonance (CMR) was performed for infarct size, MVO and IMH assessment. Median infarct size was 24.6% Interquartile range (IQR) [12.0-43.5] of LV mass and edema was 13.2% IQR [7.7-36.1] of LV mass. IL-6 reached a peak at H24 (5.6 pg/mL interquartile range (IQR) [2.5-17.5]), CRP at H48 (11.7 mg/L IQR [7.1-69.2]), fibrinogen one week after admission (4.4 g/L IQR [3.8-6.7]) and neutrophils at H12 (9.0 G/L IQR [6.5-12.7]). MVO was present in 11 patients (55% of the study population) and hemorrhage in 7 patients (35%). Patients with IMH had significantly higher IL-6, CRP, fibrinogen, and neutrophils levels compared to patients without IMH. Patients with persistent MVO had significantly higher CRP, fibrinogen and neutrophils level compared to patients without MVO, but identical IL-6 kinetics.ConclusionIn human patients with acute myocardial infarction, intramyocardial hemorrhage appears to have a stronger relationship with inflammatory biomarker release compared to persistent MVO. Attenuating myocardial hemorrhage may be a novel target in future adjunctive STEMI treatments.
| S-EPMC7842962 | biostudies-literature
Project description:Postconditioning and cyclosporine A prevent mitochondrial permeability transition pore opening providing cardioprotection during ischemia/reperfusion. Whether microvascular obstruction is affected by these interventions is largely unknown. Pigs subjected to coronary occlusion for 1 h followed by 3 h of reperfusion were assigned to control (n = 8), postconditioning (n = 9) or cyclosporine A intravenous infusion 10-15 min before the end of ischemia (n = 8). Postconditioning was induced by 8 cycles of repeated 30-s balloon inflation and deflation. After 3 h of reperfusion magnetic resonance imaging, triphenyltetrazolium chloride/Evans blue staining and histopathology were performed. Microvascular obstruction (MVO, percentage of gadolinium-hyperenhanced area) was measured early (3 min) and late (12 min) after contrast injection. Infarct size with double staining was smaller in cyclosporine (46.2 ± 3.1%, P = 0.016) and postconditioning pigs (47.6 ± 3.9%, P = 0.008) versus controls (53.8 ± 4.1%). Late MVO was significantly reduced by cyclosporine (13.9 ± 9.6%, P = 0.047) but not postconditioning (23.6 ± 11.7%, P = 0.66) when compared with controls (32.0 ± 16.9%). Myocardial blood flow in the late MVO was improved with cyclosporine versus controls (0.30 ± 0.06 vs 0.21 ± 0.03 ml/g/min, P = 0.002) and was inversely correlated with late-MVO extent (R(2) = 0.93, P < 0.0001). Deterioration of left ventricular ejection fraction (LVEF) between baseline and 3 h of reperfusion was smaller with cyclosporine (-7.9 ± 2.4%, P = 0.008) but not postconditioning (-12.0 ± 5.5%, P = 0.22) when compared with controls (-16.4 ± 5.5%). In the three groups, infarct size (β = -0.69, P < 0.001) and late MVO (β = -0.33, P = 0.02) were independent predictors of LVEF deterioration following ischemia/reperfusion (R(2) = 0.73, P < 0.001). Despite both cyclosporine A and postconditioning reduce infarct size, only cyclosporine A infusion had a beneficial effect on microvascular damage and was associated with better preserved LV function when compared with controls.
| S-EPMC4342514 | biostudies-literature
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.
| S-EPMC6201480 | biostudies-literature
Project description:BackgroundOwing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship.MethodsFirstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation.ResultsThe increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation.ConclusionsOur work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.
| S-EPMC11227217 | biostudies-literature
Project description:BackgroundIn the process of percutaneous coronary intervention (PCI), patients with ST-segment elevation myocardial infarction (STEMI) may receive large doses of the iodine contrast agent. Some adverse events may be aroused if the patients receive the gadolinium agents. We investigate the association between cine cardiac magnetic resonance (CMR)-based radiomics signature and microvascular obstruction (MVO) in patients with STEMI.MethodsA total of 116 STEMI patients who received continuous CMR within 6 days after PCI were retrospectively included in this study. According to the late gadolinium enhancement (LGE) of CMR, the myocardial infarction (MI) was divided into with and without MVO. Radiomic features were extracted from cine CMR images and the least absolute shrinkage and selectionator operator (LASSO) algorithm was used for features selection and radiomic signatures construction. Binary logistic regression was used to assess association between radiomic signatures and MVO with adjusted for baseline clinical characteristics.ResultsOf 116 patients with STEMI, MI with MVO was found in 50 patients and MI without MVO was found in 66 patients. LASSO regression selected five radiomics features for radiomics signature construction. Logistic regression revealed that radiomics score, high sensitivity C-reactive protein (hs-CRP) and creatine phosphokinases (CPK) were independent risk factors for MVO with odds ratio (OR) of 4.41 (95% CI: 2.26-9.93), 1.018 (95% CI: 1.006-1.034) and 1.0007 (95% CI: 1.0004-1.0012), respectively. Area under curve (AUC) of receiver operating characteristic (ROC) of radiomics score to predict MVO was 0.75 (95% CI: 0.68-0.85).ConclusionsCine CMR-based radiomics signature was an independent predictive factor of MVO in patients with STEMI, which showed the potential of this contrast free radiomics signature to be an imaging biomarker for MVO.
| S-EPMC9096300 | biostudies-literature
Project description:BackgroundThe ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction.Methods and resultsTen dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm x 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1+/-7.2% versus 20.4+/-7.4%, mean difference 0.7%; chronic infarcts 4.15+/-1.93% versus 4.92+/-2.06%, mean difference -0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred approximately 5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow.ConclusionsThe spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.
| S-EPMC3410562 | biostudies-literature
Project description:Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI. Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI. Histology was used to assess iron deposition and to examine relationships between iron content with macrophage infiltration, proinflammatory cytokine synthesis, and matrix metalloproteinase activation. Atomic resolution transmission electron microscopy was used to determine iron crystallinity, and energy-dispersive X-ray spectroscopy was used to identify the chemical composition of the iron composite. PMO with or without reperfusion hemorrhage led to chronic iron deposition, and the extent of this deposition was strongly related to PMO volume (r>0.8). Iron deposits were found within macrophages as aggregates of nanocrystals (≈2.5 nm diameter) in the ferric state. Extent of iron deposits was strongly correlated with proinflammatory burden, collagen-degrading enzyme activity, infarct resorption, and adverse structural remodeling (r>0.5). Crystallized iron deposition from PMO is directly related to proinflammatory burden, infarct resorption, and adverse left ventricular remodeling in the chronic phase of MI in canines. Therapeutic strategies to combat adverse remodeling could potentially benefit from taking into account the chronic iron-driven inflammatory process.
| S-EPMC5703213 | biostudies-literature
Project description:BackgroundMicrovascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE.MethodsPatients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort.ResultsForty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO-), and 314 (41%) segments showed no LGE (i.e., LGE-). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO-, and LGE-) showed an AUC = 0.764 and SCS cut-off value was -11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO- vs. LGE-) AUC = 0.848 and SCS with a cut-off value of -13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%.ConclusionSegmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI.
| S-EPMC9329615 | biostudies-literature