Extent Of Microvascular Obstruction Research Articles

Prognostic value of multiparametric cardiac magnetic resonance after revascularized STEMI

Abstract Despite early revascularization of STEMI through angioplasty, the prognosis following STEMI remains poor for a non-negligible percentage of patients (1). In this setting, multiple imaging parameters have demonstrated their prognostic value. The aim of the present study is to evaluate which of these parameters are the most potent predictors of events following revascularized STEMI. Methods A prospective observational study was conducted, including a cohort of revascularized STEMI patients and who underwent cardiac MRI during the first week. The protocol included cardiac functional analysis and with b-SSFP sequences for evaluation of volumes, mass, ejection fraction and also circumferential and radial strain with feature tracking. STIR sequences were used to assess edema and salvaged myocardium, IR-FGE sequences were employed for evaluation of necrosis size and microvascular obstruction. Intra-infarct hemorrhage assessment was performed using T2* mapping sequences as previosly described (2,3,4) . A semi-automatic analysis was conducted, considering as microvascular obstruction segments with hypointensity in the infarct core and as segments with hemorrhage those with a T2* less than 20 ms. The association of imaging parameters with cardiovascular events in the first year following STEMI was studied using ROC curves. Variables with significant association were analyzed using a multivariate logistic regression model. Results Ninety-four patients with a mean age of 63 (SD 13) years were included. Nine of them had cardiovascular events in the first year and two of them died. The relative extent of necrosis and microvascular obstruction, minimal radial strain, left ventricular ejection fraction (LVEF) and indexed left ventricular end- systolic volume (ILVESV) showed significant association with cardiovascular events after STEMI. Variables with significant association were entered into a multivariate predictive model, revealing that the extent of microvascular obstruction (OR: 1.9, p=0.02) and the left ventricular end-systolic volume (OR: 1.04, p<0.01) are the only independent predictors of cardiovascular events following STEMI. Conclusion Although multiple imaging parameters have shown prognostic value after STEMI, the ILVESV and the extent of microvascular obstruction are the only independent predictors of events following STEMI.Multiparametric cardiac MR in STEMIAREA UNDER ROC CURVE OF CMR PARAMETERS

Microcirculatory resistance after primary percutaneous coronary intervention predicts residual myocardial damage: a post hoc analysis from the CLEVER-ACS trial

Abstract Introduction Coronary microvascular dysfunction has been associated with adverse cardiovascular events following acute myocardial infarction. This study evaluates the role of the angiography-derived index of microcirculatory resistance (angio-IMR) in predicting myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and Methods In this post hoc analysis of the Controlled Level Everolimus in Acute Coronary Syndromes (CLEVER-ACS) trial, the associations between post-PCI angio-IMR of infarct-related coronary arteries (IRAs) and infarct size, microvascular obstruction (MVO), and left ventricle ejection fraction (LVEF) at 30 days as assessed with cardiac magnetic resonance (CMR) imaging were investigated. High post-PCI angio-IMR value was defined as a value >40 U. In non-IRAs angio-IMR was measured before the IRA-PCI. Results A total of 52 IRAs and 94 non-IRAs of 52 patients were included in the analysis. Post-PCI Angio-IMR was 41.5 (IQR 28.5–55.7) U in IRAs and pre-PCI Angio-IMR was 43.7 (31.7–54.0) U in non-IRAs (p = 0.70). Patients with high post-PCI angio-IMR (52%) exhibited a larger myocardial infarct size (36.0 [23.0–52.5] g vs. 14.5 [6.50–26.5] g, p < 0.001) and a lower LVEF (46.5 [39.5–49.5] % vs. 55.0 [48.0–61.4] %, p = 0.002) at 30 days as compared to those with low post-PCI angio-IMR values. Post-PCI angio-IMR correlated with myocardial infarct size (r = 0.45, p = 0.001) and extent of MVO (r = 0.40, p = 0.004) at 30 days. Post-PCI angio-IMR predicted myocardial infarct size (AUC = 0.78 [0.65–0.92], p = 0.001) and extent of MVO (AUC = 0.74 [0.60–0.89], p = 0.009) at 30 days. Conclusion In patients with STEMI undergoing PCI, post-PCI angio-IMR was identified as independent predictor of myocardial infarct size and extent of MVO at 30 days. The assessment of post-PCI angio-IMR values may represent a novel tool for early risk stratification of patients with STEMI.Central illustration

Assessment of microvascular occlusion in re-perfused myocardial infarction patients using cardiac magnetic resonance

Abstract Background and objective Primary percutaneous coronary intervention (PPCI) is the gold standard for myocardial reperfusion in ST-segment elevation myocardial infarction (STEMI). Numerous studies have shown that thrombus aspiration can prevent distal embolization, reducing the risk of microvascular obstruction (MVO). Cardiac magnetic resonance (CMR) is considered the gold standard for evaluation of MVO. The aim of this study is to evaluate the efficacy of thrombus aspiration as adjunctive technique to primary PCI, in reducing incidence and extent of MVO in STEMI patients evaluated by CMR. Methods Ninety-three patients with heavy thrombus burden were enrolled in this study, sixty-five met our inclusion criteria. Aspiration thrombectomy followed by PCI was done for thirty-one patients (aspiration group) and conventional PCI, without aspiration thrombectomy, was done for thirty-four patients (conventional group). Primary end points were occurrence and extent of microvascular obstruction (MVO) evaluated by cardiac magnetic resonance (CMR). Results The incidence of microvascular obstruction (MVO) was significantly higher in conventional group (18 patients, 52.9%) when compared with aspiration group (7 patients, 22.6%) (p-value = 0.012). Moreover, significant difference existed between studied groups as regard MVO extent. In aspiration group, MVO extended to > 4 segments in 3 patients (9.7%) while in conventional group, MVO extended to > 4 segments in 13 patients (38.2%) (p-value = 0.012). Conclusion Aspiration thrombectomy as adjunctive technique to PCI in STEMI population maintains the integrity of coronary microvasculature and reduces both incidence and extent of MVO.

The distribution and mass index of epicardial adipose tissue were correlated with microvascular obstruction formation in patients with ST-segment elevation myocardial infarction

Abstract Introduction Epicardial adipose tissue (EAT), refers to a metabolically active fat depot between the visceral pericardium and the outer margin of the myocardium. EAT has gradually emerged as a novel target for risk stratification of coronary artery disease due to its distinctive location and multifaceted metabolic properties. Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) is identified as an independent risk factor for poor prognosis in patients with acute myocardial infarction. However, the clinical implications of EAT in MVO formation in patients with ST-segment elevation myocardial infarction (STEMI) remain unclear. Recently, cardiac magnetic resonance (CMR) has emerged as the gold standard technique to detect the extent of MVO and evaluate EAT parameters. Purpose This study aimed to evaluate the correlation between EAT accumulation and MVO occurrence detected by CMR in STEMI patients. Methods A total of 129 STEMI patients who underwent pPCI successfully were enrolled. Clinical characteristics including demographic characteristics, cardiovascular risk factors, laboratory data and angiographic parameters were recorded from each patient by 1 trained physician. All patients underwent CMR within 1 week following pPCI to evaluate infarct size, MVO volume and EAT distribution. All CMR data were transferred to Q-MASS MR 8.1 imaging system (Medis, Leiden, The Netherlands) and interpreted twice by 2 expert radiologists who were blinded to the angiographic and clinical data of patients. Results Compared to STEMI patients without MVO, STEMI patients with MVO presented with higher peak troponin T levels, increase of neutrophil lymphocyte ratio (NLR) and C-reactive protein (CRP), larger infarct size and compromised left ventricular ejection fraction. Total EAT volume, EAT mass index, left atrioventricular EAT volume, left atrioventricular EAT mass index and thickness of EAT in the left atrioventricular groove were unanimously associated with the occurrence of MVO. The left atrioventricular EAT mass index in STEMI patients with MVO were significantly larger than that in STEMI patients without MVO (24.72±5.049 g/m2 vs 18.63±3.670 g/m2, P<0.001). Multivariate logistic regression analysis demonstrated that NLR, peak troponin T levels and left atrioventricular EAT mass index were independent predictors of MVO. LV EAT mass index showed a robust and independent relationship with MVO formation and a cutoff value >21.5192 g/m2 predicted the presence of MVO with a sensitivity and specificity of 79.5% and 80.4%, respectively. Conclusions Left atrioventricular EAT mass index is an independent predictor of MVO. Measurement of EAT using CMR could be used for risk stratification and might be a promising target in developing new therapies to reduce myocardial reperfusion injury in patients with STEMI.

Glycoprotein IIb/IIIa Inhibitors in Acute Myocardial Infarction and Angiographic Microvascular Obstruction: The REVERSE-FLOW Trial.

Glycoprotein (GP) IIb/IIIa inhibitors are recommended in acute myocardial infarction (AMI) for bailout treatment in case of angiographic microvascular obstruction (MVO), also termed no-reflow phenomenon, after percutaneous coronary intervention (PCI) with, however, lacking evidence (class IIa, level C). The investigator-initiated, international, multicenter REVERSE-FLOW trial randomized 120 patients with AMI and Thrombolysis In Myocardial Infarction flow grade ≤2 after primary PCI to optimal medical therapy with or without GP IIb/IIIa inhibitor. The primary endpoint was infarct size (%LV) assessed by cardiac magnetic resonance (CMR). Secondary endpoints included CMR-derived MVO and 30-day adverse clinical events. The trial is registered with ClinicalTrials.gov: NCT02739711. The population was predominantly male (76.7%) with a median age of 66 years and ST-elevation myocardial infarction in 73.3% of patients. Clinical and angiographic characteristics were well balanced between the cohorts. Patients in the treatment group (n=62) received eptifibatide (n=41) or tirofiban (n=21). Infarct size assessed by CMR imaging was similar in both study groups (25.4% of left ventricular mass [LV] vs. 25.2%LV; p=0.386). However, the number of patients with evidence of CMR-derived MVO (74.5% vs. 92.2%; p=0.017) and the extent of MVO (2.1%LV vs. 3.4%LV; p=0.025) were significantly reduced in the GP IIb/IIIa inhibitor group compared to controls. Thirty-day outcome showed an increased bleeding risk after GP IIb/IIIa inhibitor administration restricted to non-life-threatening bleedings (22.6% vs. 6.9%; p=0.016) without differences in all-cause mortality (4.8% vs. 3.4%; p=0.703). Bailout GP IIb/IIIa inhibition in AMI patients with angiographic MVO failed to reduce the primary endpoint infarct size but decreased CMR-derived MVO and led to an increase in non-fatal bleeding events.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

Microvascular recovery with ultrasound in myocardial infarction post-PCI trial.

Persistent microvascular obstruction (MVO) after successful percutaneous coronary intervention (PCI) in acute ST segment elevation myocardial infarction (STEMI) has been well-described. MVO predicts lack of recovery of left ventricular function and increased mortality. Sonothrombolysis utilizing diagnostic ultrasound induced cavitation of commercially available microbubble contrast has been effective at reducing infarct size and improving left ventricular ejection fraction (LVEF) when performed both pre- and post-PCI. However, the effectiveness of post-PCI sonothrombolysis alone after successful PCI has not been demonstrated. A prospective randomized controlled trial was performed in 50 consecutive consenting patients with anterior STEMI who underwent a continuous microbubble infusion immediately following successful PCI. Intermittent high mechanical index (MI) impulses were applied only in the sonthrombolysis group. Delayed enhancement magnetic resonance imaging (MRI) was performed at 48h and again at 6-8weeks to assess for differences in infarct size, LVEF, and MVO. There were no differences between groups in age, gender, and cardiovascular risk factors. Significant (>2 segments) MVO following successful PCI was observed in 66% of patients. Although sonothrombolysis reduced the extent of MVO acutely, there were no differences in infarct size, LVEF, or extent of MVO by MRI at 48h. Twenty-eight patients returned for a follow up MRI at 6-8weeks. LVEF improved only in the sonothrombolysis group (∆LVEF 7.81±4.57% with sonothrombolysis vs. 1.77±7.02% for low MI only, p=.011). Post-PCI sonothrombolysis had minimal effect on reducing myocardial infarct size but improved left ventricular systolic function in patients with acute anterior wall STEMI.

Association of stress hyperglycemia ratio with left ventricular function and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a 3.0 T cardiac magnetic resonance study.

Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio (SHR). Impaired left ventricular function and microvascular obstruction (MVO) diagnosed using cardiac magnetic resonance (CMR) have also been proven to be linked to poor prognosis in patients with AMI and aid in risk stratification. However, there have been no studies on the correlation between fasting SHR and left ventricular function and MVO in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Therefore, this study aimed to investigate the additive effect of fasting SHR on left ventricular function and global deformation in patients with ASTEMI and to explore the association between fasting SHR and MVO. Consecutive patients who underwent CMR at index admission (3-7 days) after primary percutaneous coronary intervention (PPCI) were enrolled in this study. Basic clinical, biochemical, and CMR data were obtained and compared among all patients grouped by fasting SHR tertiles: SHR1: SHR < 0.85; SHR2: 0.85 ≤ SHR < 1.01; and SHR3: SHR ≥ 1.01. Spearman's rho (r) was used to assess the relationship between fasting SHR and left ventricular function, myocardial strain, and the extent of MVO. Multivariable linear regression analysis was performed to evaluate the determinants of left ventricular function and myocardial strain impairment in all patients with AMI. Univariable and multivariable regression analyses were performed to investigate the correlation between fasting SHR and the presence and extent of MVO in patients with AMI and those with AMI and diabetes mellitus (DM). A total of 357 patients with ASTEMI were enrolled in this study. Left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI) were significantly lower in SHR2 and SHR3 than in SHR1. Compared with SHR1 and SHR2 groups, left ventricular strain was lower in SHR3, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strains. Fasting SHR were negatively correlated with LVEF, LVGFI, and GRS (r = - 0.252; r = - 0.261; and r = - 0.245; all P<0.001) and positively correlated with GCS (r = 0.221) and GLS (r = 0.249; all P <0.001). Multivariable linear regression analysis showed that fasting SHR was an independent determinant of impaired LVEF, LVGFI, GRS, and GLS. Furthermore, multivariable regression analysis after adjusting for covariates signified that fasting SHR was associated with the presence and extent of MVO in patients with AMI and those with AMI and DM. Fasting SHR in patients with ASTEMI successfully treated using PPCI is independently associated with impaired cardiac function and MVO. In patients with AMI and DM, fasting SHR is an independent determinant of the presence and extent of MVO.

Microvascular Obstruction in Patients With Anterior STEMI Treated With Supersaturated Oxygen

BackgroundSupersaturated oxygen (SSO2) delivered into the left anterior descending coronary artery after percutaneous coronary intervention (PCI) for anterior ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size, but its effects on microvascular obstruction (MVO) are unknown. The aim of this study was to compare MVO in patients with anterior STEMI treated with SSO2 after successful primary PCI from 2 studies (the optimized SSO2 pilot and IC-HOT) with similar patients from 7 randomized trials who underwent primary PCI without SSO2 treatment. MethodsA total of 874 patients with anterior STEMI who underwent MVO assessment using cardiac magnetic resonance imaging within 10 days after primary PCI were included, of whom 90 patients (10.3%) were treated with SSO2. The primary end point was the extent of MVO as a continuous measure in a weighted multivariable model. The secondary end point was the presence of MVO. ResultsSSO2 therapy was independently associated with a lower extent of MVO compared with no SSO2 therapy (coefficient, −1.35; 95% CI, −2.58 to −0.11; P = .03). SSO2 therapy was also associated with a borderline lower risk of any MVO (adjusted odds ratio, 0.56; 95% CI, 0.31-1.00; P = .051). ConclusionsIn the present individual patient data pooled analysis from 9 studies, SSO2 therapy was associated with less MVO after successful primary PCI for anterior STEMI.

Growth differentiation factor-15 as a negative predictor for microvascular obstruction in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

Growth differentiation factor-15 (GDF-15) is an anti-inflammatory cytokine with cardioprotective effects, but circulating GDF-15 concentration predicts adverse cardiovascular outcomes in clinical settings. Microvascular obstruction (MVO) formation contributed to poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI). We aimed to investigate GDF-15 concentration in relation to cardiac magnetic resonance (CMR)-derived MVO in STEMI patients after pPCI, which might help better understand the role of GDF-15 in STEMI. GDF-15 levels at 6h after pPCI and MVO extent at day 5 ± 2 after pPCI were measured in 74 STEMI patients (mean age 60.3 ± 12.8years, 86.5% men). The adjusted association of GDF-15 with MVO was analyzed with MVO treated as a categorized variable (extensive MVO, defined as MVO extent ≥ 2.6% of left ventricular (LV)) and a continuous variable (MVO mass, % of LV), respectively, in multivariate logistic and linear regression models. 41.9% of the patients developed extensive MVO after pPCI. In multivariate analysis, the odds ratio (95% confidential interval (CI)) of each standard deviation (SD) increase in GDF-15 for developing extensive MVO was 0.46 (0.21, 0.82), p = 0.02). Consistently, when MVO was used a continuous variable, each SD increase in GDF-15 was associated with a substantially lower MVO mass (β - 0.42, standard error 0.19, p = 0.03). GDF-15 was a negative predictor for MVO in STEMI patients after pPCI. The observation was consistent with results from experiment studies, suggesting a potential protective effect of GDF-15 against cardiac injury.

Time of day dependent symptom onset is not associated with left ventricular function and myocardial damage after ST-segment elevation myocardial infarction

Abstract Background Circadian processes are suggested to influence ischemic injury in ST-segment elevation myocardial infarction (STEMI). Observational data suspect a circadian dependence of the occurrence of microvascular obstruction (MVO) in patients with STEMI. However, these observations derive from a small sample size and circadian variations in left ventricular function and myocardial damage after STEMI are still a matter of controversy. Purpose We aimed to investigate the association of time of day dependent symptom onset with left ventricular ejection fraction (LVEF), infarct size (IS) and MVO in a large cohort of STEMI patients treated with primary percutaneous coronary intervention (PCI). Methods This observational study investigated acute STEMI patients treated with primary PCI. Cardiac magnetic resonance (CMR) imaging was performed within 1 week after the index event for the determination of left ventricular function and infarct characteristics. The time of symptom onset was used to discriminate patients according to LVEF, IS as well as MVO occurrence and extent over a 24 hours cycle to evaluate circadian behavior. Results In final analysis, 889 acute STEMI patients treated with primary PCI with a delay of 189 [120-315] minutes were included. Median age of the overall cohort was 57 [51-66] years and 17% were female. Median LVEF was 49 [42-55]%, IS assumed 15.5 [8.0-24.7]% of left ventricular myocardial mass (LVMM) and MVO occurred in 57% of STEMI patients. No hourly differences between symptom onset and MVO occurrence (p=0.108), MVO extent (p=0.735), LVEF (p=0.644) and IS (p=0.722) have been evaluated. When comparing 3 hourly segments of symptom onset, no variations in MVO occurrence (p=0.114), MVO extent (p=0.308), LVEF (p=0.547) and IS (p=0.405) were observed. Conclusions No circadian variations in symptom onset and the occurrence and extent of MVO, LVEF and IS were observed in this large cohort of STEMI patients treated with primary PCI. Further research is needed to investigate the complex interplay between circadian processes and ischemic injury in this patient population.

A pilot randomized controlled trial of novel reperfusion method in patients of acute st elevation myocardial infarction during primary percutaneous coronary intervention

Abstract Objectives This study was conducted to explore the feasibility, clinical safety and potential effects of a novel reperfusion method, Volume-Controlled Reperfusion (VCR) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Background Reperfusion injury is associated with larger infarct size (IS) and drawback of long-term overcome. Microvascular obstruction (MVO) as detected on late gadolinium-enhanced cardiovascular magnetic resonance (LGE-CMR) is the most used index for assessment of reperfusion injury. To date, there is no feasible gradual reperfusion method in primary PCI setting. VCR is an original reperfusion method feasible in primary PCI for both accurate gradual reperfusion and intermittent flow. Methods A total of 60 patients with STEMI presenting within 12 h of symptom onset undergoing PPCI were randomized enrolled, 30 patients in VCR group and 30 patients in control group with routine PCI only. VCR was performed with the dual catheter technique, 10ml of artery blood diluted with10ml of heparin saline infused via manual aspiration catheter at speed of 20ml/min for 10 rounds after suspending the antegrade flow using a prophylactic inflated balloon. Then, routine PCI procedure as usual. The primary endpoint was major adverse cardiac events (MACE) during hospitalization, the main second endpoint was the MVO extent difference measured on day 5-7 post-procedure. Results Baseline characteristics were well matched between two groups. No major adverse cardiac events (MACE) found in-hospital or 30 days followed up. There were no complications associated with VCR procedure. 43 patients had LGE-CMR exam (22 in Control group, 21 in VCR group, among them, 14/22 were anterior wall control and 14/21 VCR). There was no significant difference in infarct size, MVO or CMR-LVEF in total patients between VCR and control. However, significant difference in CMR-LVEF was noted between control and VCR anterior wall subgroup (40.53 ± 7.39 vs50.55 ± 7.55; P=0.002), the average of MVO and MVO of infarct size were smaller in VCR group while no significant difference. Conclusions This is the pilot RCT study showed VCR method was feasibility and clinical safe among patients with acute STEMI during PPCI and 30 days followed up, indicated potential attenuate effect in reperfusion injury as well. Staged II study is needed to verify clinical benefit.VCR illustrationLGE-CMR figure

Microvascular Obstruction in Acute Myocardial Infarction, a Potential Therapeutic Target.

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.

Coronary No-Reflow after Primary Percutaneous Coronary Intervention-Current Knowledge on Pathophysiology, Diagnosis, Clinical Impact and Therapy.

Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently, the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.

Impact of Persistent Microvascular Obstruction Late After STEMI on Adverse LV Remodeling: A CMR Study

BackgroundLittle is known about the occurrence and implications of persistent microvascular obstruction (MVO) after reperfused ST-segment elevation myocardial infarction (STEMI). ObjectivesThe authors used cardiac magnetic resonance (CMR) to characterize the impact of persistent MVO on adverse left ventricular remodeling (ALVR). MethodsA prospective registry of 471 STEMI patients underwent CMR 7 (IQR: 5-10) days and 198 (IQR: 167-231) days after infarction. MVO (≥1 segment) and ALVR (relative increase >15% at follow-up CMR) of left ventricular end-diastolic index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were determined. ResultsOne-week MVO occurred in 209 patients (44%) and persisted in 30 (6%). The extent of MVO (P = 0.026) and intramyocardial hemorrhage (P = 0.001) at 1 week were independently associated with the magnitude of MVO at follow-up CMR. Compared with patients without MVO (n = 262, 56%) or with MVO only at 1 week (n = 179, 38%), those with persistent MVO at follow-up (n = 30, 6%) showed higher rates of ALVR-LVEDVI (22%, 27%, and 50%; P = 0.003) and ALVR-LVESVI (20%, 21%, and 53%; P < 0.001). After adjustment, persistent MVO at follow-up (≥1 segment) was independently associated with ΔLVEDVI (relative increase, %) (P < 0.001) and ΔLVESVI (P < 0.001). Compared with a 1:1 propensity score–matched population on CMR variables made up of 30 patients with MVO only at 1 week, patients with persistent MVO more frequently displayed ALVR-LVEDVI (12% vs 50%; P = 0.003) and ALVR-LVESVI (12% vs 53%; P = 0.001). ConclusionsMVO persists in a small percentage of patients in chronic phase after STEMI and exerts deleterious effects in terms of LV remodeling. These findings fuel the need for further research on microvascular injury repair.

Pre-stenting residual thrombotic volume assessed by dual quantitative coronary angiography predicts microvascular obstruction in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Microvascular obstruction (MVO) is a frequent occurrence after primary percutaneous coronary intervention (pPCI), and is associated with adverse left ventricular remodeling and worse clinical outcome. Distal embolization of thrombotic material is one of the most important underlying mechanisms. The aim of this study was to investigate the relation between the thrombotic volume evaluated by dual quantitative coronary angiography (QCA) prior to stenting and the occurrence of MVO as assessed by cardiac magnetic resonance (CMR). Forty-eight patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI and receiving CMR within 7 days from admission were included. Pre-stenting residual thrombus volume at the site of the culprit lesion was measured by applying automated edge detection and video-assisted densitometry techniques (i.e., dual-QCA), and patients were categorized into tertiles of thrombus volume. The presence of delayed-enhancement MVO, as well as its extent (MVO mass), were assessed by CMR. Pre-stenting dual-QCA thrombus volume was significantly greater in patients with MVO than in those without (5.85 mm3 [2.05-16.71] vs. 1.88 mm3 [1.03-6.92], P=0.009). Patients in the highest tertile showed greater MVO mass compared to those in the mid and lowest tertiles (113.3 gr [0.0-203.8] vs. 58.5 g [0.00-144.4] vs. 0.0 g [0.0-60.225], respectively; P=0.031). The best cut-off value of dual-QCA thrombus volume for prediction of MVO was 2.07 mm3 (AUC: 0.720). The addition of dual-QCA thrombus volume to the traditional angiographic indices of no-reflow enhanced the prediction of MVO by CMR (R=0.752). Pre-stenting dual-QCA thrombus volume is associated with the presence and extent of MVO detected by CMR in patients with STEMI. This methodology may aid the identification of patients at higher risk of MVO and guide adoption of preventive strategies.

Impact of persistent MVO late after STEMI on adverse left ventricular remodelling: a CMR study

Abstract Background Despite successful revascularization at the epicardial level, microvascular obstruction (MVO) appears soon after reperfusion in up to 50% of cases. Early MVO has been solidly associated with adverse resulting cardiac structure and heightened risk of future cardiovascular events. Although clinical and experimental studies demostrated the spontaneous repair of MVO, little is known about the occurrence and implications of persistent MVO late after infarction. Purpose We used cardiovascular magnetic resonance (CMR) to characterize the impact of persistent MVO late after reperfused ST-segment elevation myocardial infarction (STEMI) on adverse left ventricular (LV) remodelling (ALVR). Methods A prospective registry of 471 STEMI patients underwent CMR 7 [5–10] and 198 [167–231] days post infarction, and MVO (&amp;gt;1 segment) and ALVR (relative increase &amp;gt;15% at follow-up CMR) of LV end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) were determined. Results One-week MVO occurred in 209 patients (44%) and persisted in 30 of these (6%). Most patients with persistent MVO (22/30, 73%) displayed extensive (&amp;gt;2.5% of LV mass) MVO at 1 week. Compared with patients without MVO (n=262, 56%) or with MVO only at 1 week (n=179, 38%), those with persistent MVO at follow-up (n=30, 6%) showed higher rates of ALVR-LVEDVI (22%, 27%, 50% p=0.003) and ALVR-LVESVI (20%, 21%, 53% p&amp;lt;0.001). After adjustment, the extent (% of LV mass) of MVO at follow-up was independently associated with ΔLVEDVI (relative increase, %) (p=0.01) and ΔLVESVI (p=0.03). Compared to a 1:1 matched population of 30 patients with MVO only at 1 week, patients with persistent MVO more frequently displayed ALVR-LVEDVI (12% vs. 50%, p=0.003) and ALVR-LVESVI (12% vs. 53%, p=0.001). Conclusion MVO persists in a small percentage of patients in chronic phase after STEMI and exerts deleterious effects in terms of LV remodelling. These findings fuel the need for further research on microvascular injury repair. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” [grant numbers PI20/00637, PI15/00531, FI18/00320, and CIBERCV16/11/00486] and by Conselleria de Educaciόn – Generalitat Valenciana (PROMETEO/2021/008).

Índice de resistencia microcirculatoria y obstrucción microvascular en la resonancia magnética cardiaca tras un IAMCEST

Introduction and objectivesThe index of microcirculatory resistance (IMR) measured after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is associated with microvascular obstruction (MVO) and adverse clinical events. To evaluate MVO after successful primary PCI for STEMI without pressure wires or hyperemic agents, we investigated the feasibility and usefulness of functional angiography-derived IMR (angio-IMR). MethodsThe current study included a total of 285 STEMI patients who underwent primary PCI and cardiac magnetic resonance (CMR). Angio-IMR of the culprit vessel after successful primary PCI was calculated using commercial software. MVO, infarct size, and myocardial salvage index were assessed using CMR, which was obtained a median of 3.0 days [interquartile range, 3.0-5.0] after primary PCI. ResultsAmong the total population, 154 patients (54.0%) showed elevated angio-IMR (> 40 U) in the culprit vessel. MVO was significantly more prevalent in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (88.3% vs 32.1%, P <.001). Infarct size, extent of MVO, and area at risk were significantly larger in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (P <.001 for all). Angio-IMR showed a significantly higher discriminatory ability for the presence of MVO than thrombolysis in myocardial infarction flow grade or myocardial blush grade (area under the curve: 0.821, 0.504, and 0.496, respectively, P <.001). ConclusionsAngio-IMR was significantly associated with CMR-derived infarct size, extent of MVO, and area at risk. An elevated angio-IMR (> 40 U) after primary PCI for STEMI was highly predictive of the presence of MVO in CMR.This trial was registered at ClnicalTrialsgov (Identifier: NCT04828681).

Functional angiography-derived index of microcirculatory resistance validated with microvascular obstruction in cardiac magnetic resonance after STEMI

Introduction and objectivesThe index of microcirculatory resistance (IMR) measured after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is associated with microvascular obstruction (MVO) and adverse clinical events. To evaluate MVO after successful primary PCI for STEMI without pressure wires or hyperemic agents, we investigated the feasibility and usefulness of functional angiography-derived IMR (angio-IMR). MethodsThe current study included a total of 285 STEMI patients who underwent primary PCI and cardiac magnetic resonance (CMR). Angio-IMR of the culprit vessel after successful primary PCI was calculated using commercial software. MVO, infarct size, and myocardial salvage index were assessed using CMR, which was obtained a median of 3.0 days [interquartile range, 3.0-5.0] after primary PCI. ResultsAmong the total population, 154 patients (54.0%) showed elevated angio-IMR (> 40 U) in the culprit vessel. MVO was significantly more prevalent in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (88.3% vs 32.1%, P <.001). Infarct size, extent of MVO, and area at risk were significantly larger in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (P <.001 for all). Angio-IMR showed a significantly higher discriminatory ability for the presence of MVO than thrombolysis in myocardial infarction flow grade or myocardial blush grade (area under the curve: 0.821, 0.504, and 0.496, respectively, P <.001). ConclusionsAngio-IMR was significantly associated with CMR-derived infarct size, extent of MVO, and area at risk. An elevated angio-IMR (> 40 U) after primary PCI for STEMI was highly predictive of the presence of MVO in CMR.This trial was registered at ClnicalTrialsgov (Identifier: NCT04828681).

Post-ST-Segment-Elevation Myocardial Infarction Platelet Reactivity Is Associated With the Extent of Microvascular Obstruction and Infarct Size as Determined by Cardiac Magnetic Resonance Imaging.

BackgroundDespite 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 ResultsWe 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).ConclusionsIn 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.