Int J Cardiovasc Imaging DOI 10.1007/s10554-014-0430-z

ORIGINAL PAPER

Microvascular obstruction in patients with non-ST-elevation myocardial infarction: a contrast-enhanced cardiac magnetic resonance study Elena Guerra • Martin Hadamitzky • Gjin Ndrepepa • Corinna Bauer • Tareq Ibrahim • Ilka Ott • Karl-Ludwig Laugwitz • Heribert Schunkert Adnan Kastrati



Received: 27 January 2014 / Accepted: 18 April 2014 Ó Springer Science+Business Media Dordrecht 2014

Abstract The aim of the study was to assess the frequency and predictive factors of microvascular obstruction (MVO) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). This study included 190 consecutive patients with NSTEMI who underwent percutaneous coronary intervention (PCI) within 24 h after admission and cardiac magnetic resonance (CMR) imaging, 4.1 days after angiography. MVO was defined using the CMR criteria. MVO was detected 26 of 190 patients (13.8 %). Patients with MVO had higher peak high-sensitivity troponin T, creatine-kinase and creatine kinasemyocardial band levels and higher proportions of those with baseline thrombolysis in myocardial infarction (TIMI) flow grade 0–1, absence of collateral circulation, post-PCI TIMI flow grade \3, myocardial blush grade \3 and angiographic no-reflow than patients without MVO. Patients with MVO had larger initial area at risk [median (25th–75th percentiles), 23.9 % (17.4–33.9 %) vs. 16.1 % (7.8–27.7 %), P = 0.018] and infarct size [11.4 % (6.6–19.2 %) vs. 1.4 % (0–4.7 %) of the left ventricle, P \ 0.001] than patients without MVO. In multivariable analysis, the culprit lesion localization in the circumflex coronary artery [adjusted odds ratio (OR) 13.71, 95 % E. Guerra  M. Hadamitzky  G. Ndrepepa  C. Bauer  I. Ott  H. Schunkert  A. Kastrati (&) Deutsches Herzzentrum Mu¨nchen, Technische Universita¨t, Lazarettstrasse 36, 80636 Munich, Germany e-mail: [email protected] T. Ibrahim  K.-L. Laugwitz 1.Medizinische Klinik rechts der Isar, Technische Universita¨t, Munich, Germany K.-L. Laugwitz  H. Schunkert  A. Kastrati DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany

confidence interval 2.91–64.58, P \ 0.001] and the infarct size [adjusted OR 3.37 (1.80–6.29), P \ 0.001, for each 5 % of the left ventricle] were independently associated with the increased risk for MVO. In patients with NSTEMI undergoing early PCI, the MVO defined by CMR imaging was present in 13.8 % of the patients. The localization of culprit lesion in the circumflex coronary artery and larger infarct size were independently associated with the increased risk for MVO. Keywords Cardiac magnetic resonance imaging  Microvascular obstruction  Non-ST elevation myocardial infarction  No-reflow

Introduction Non ST-elevation acute myocardial infarction (NSTEMI) comprises about one-third of all acute coronary syndromes and it shows a considerable heterogeneity in its clinical manifestation [1]. NSTEMI represents a high-risk condition that is associated with significant subsequent morbidity and mortality. While the 30-days mortality in patients with NSTEMI is significantly lower than in STEMI, this difference narrows at 6 months and disappears at 1 year while the re-infarction rate at 6 months is similar between STEMI and NSTEMI [2, 3]. Thus, risk stratification of patients with NSTEMI to identify patients at increased risk for future adverse events or select those who may benefit mostly from a more aggressive treatment strategy is of considerable clinical interest. For this reason several risk stratification tools have been developed including the thrombolysis in myocardial infarction (TIMI) risk score [4] and the Global Registry of Acute Cardiac Events (GRACE) risk score [5]. However, the prognosis of patients with

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NSTEMI appears to be quite variable even if their risk was stratified by the current risk scores [6]. Although the restoration of epicardial TIMI flow after revascularization at the infarct-related artery is an important predictor of outcome it may be not synonymous with the successful reperfusion since it may not reflect tissue reperfusion [7, 8]. It has been found that a sizeable portion of patients lack perfusion at tissue level despite early recanalization of the epicardial coronary artery and restoration of normal TIMI flow [9] and the terms no-reflow phenomenon or microvascular obstruction (MVO) have been coined to characterize this situation. Many studies have shown that the presence of MVO is strongly associated with adverse LV-remodeling and worse prognosis [10–13]. The majority of studies that have evaluated the predictors of MVO were performed in patients with ST-segment elevation myocardial infarction (STEMI) [14, 15]. Only few studies have assessed the correlates or the impact of MVO in patients with NSTEMI. The studies included rather limited numbers of patients and their findings were controversial [16, 17]. Cardiac magnetic resonance (CMR) is a highly sensitive technique that allows in vivo visualization and quantification of MVO in patients with acute myocardial infarction. Several studies have showed that MRI-determined MVO predicts cardiovascular adverse events including left ventricular remodeling and long-term prognosis [14, 18]. Our study had two objectives: first to assess MVO presence in patients with NSTEMI undergoing an early revascularization with percutaneous coronary intervention (PCI); and, second to investigate the relationship between MVO and clinical, angiographic and other CMR parameters and identify possible predictive factors of MVO in patients with NSTEMI.

Methods Patients This study included 190 consecutive patients with NSTEMI ([18 years of age) who underwent coronary angiography, early PCI (within 24 h after admission) and CMR imaging (median 4.1 days after the coronary angiography). The diagnosis of NSTEMI was based on the presence of typical symptoms of acute coronary syndrome evolving over the last 48 h, without persistent ST-segment elevation on 12-lead electrocardiogram and elevation of high-sensitivity cardiac troponin T (hs-TnT) exceeding the 99th percentile of the reference control group ([0.0014 ng/ml; high-sensitivity troponin T assay, Roche Diagnostics). The main exclusion criteria were: presence of cardiogenic

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shock, acute pericarditis and contraindication to CMR imaging (pacemaker, internal defibrillator or other incompatible intracorporal foreign bodies, creatinine clearance below 50 ml/min, hemodynamic instability for [7 days after infarction and claustrophobia). Patients with previous myocardial infarction or PCI were included if the prior event was located in a territory that was different from the current ischemic event. All patients gave informed consent for coronary angiography, PCI, blood sampling and CMR. The study conforms to the Declaration of Helsinki. PCI (predominantly coronary stenting) was performed as per standard practice. Before PCI procedure, all patients received 325–500 mg of aspirin and a loading dose of 600 mg of clopidogrel. Unfractionated heparin or bivalirudin were used peri-procedurally. Post-PCI antithrombotic therapy included aspirin (80–325 mg/day continuously) and clopidogrel (150 mg/day until discharge but for no longer than 3 days followed by 75 mg/day for C1 month if baremetal stents were implanted and C6 months if drug-eluting stents were used. Other medications were left at the discretion of the patient’s attending physician. Magnetic resonance study CMR was performed on a 1.5-T system (Siemens Avanto, Siemens Medical Solutions, Erlangen, Germany) equipped with a dedicated cardiac phased-array surface coil. For image acquisition, patients were positioned in a supine position, and images were acquired at repeated end-expiratory breath holds with ECG gating. Area at risk was assessed using a T2-weighted turbo spin echo sequence acquired before contrast injection (slice thickness 8 mm; repetition time 2 RR intervals; echo time 99 ms; image matrix 145 9 192). The infarct scar was assessed 15 min after injection of 0.2 mmol/kg body weight of dimeglumingadopentetat (Magnevist, Bayer HealthCare Pharmaceuticals, Berlin, Germany, until June 2009 and Magnograf, Marotrast, Jena, Germany, thereafter) on T1-weighted inversionrecovery turbo fast low-angle shot sequence (slice thickness 8 mm; repetition time 4.0 ms; echo time 1.5 ms; image matrix 175 9 256; flip angle 30°). The inversion time was individually adjusted to null normal myocardium. For both acquisitions, contiguous short-axis slices of the LV from base to apex, as well as 2- and 4-chamber views of the LV, were acquired at the same location. The CMR study was performed 4.1 days [interquartile range (IQR) 3.6–4.9 days] after angiography. For defect quantification, endocardial and epicardial contours were manually traced on each of the short-axis slices by an experienced reader. The defect size was then calculated automatically by comparison with manually marked, healthy remote myocardium and was expressed as the percentage of total LV myocardial volume

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[19]. Area at risk was defined as a region of hyperenhanced myocardium with signal intensity above 2 standard deviations (SD) of healthy remote myocardium as proposed by Friedrich et al. [20]. For infarcted myocardium, the same algorithm was used with a threshold of 6 SD. In consensus with previous studies, a defect was required to have at least 10 contiguous myocardial pixels of increased signal intensity [20–22]. MVO was defined as a dark zone (area of hypoenhancement) within the infarcted myocardium usually located in the subendocardium and showing a variable degree of transmurality. The MVO area was delineated manually, since there is no robust automated detection algorithm available. Care was taken not to miss tissue between the manually delineated and the automatically detected scar areas. MVO was included in the infarct size calculation. Angiographic evaluation Coronary angiography was performed according to standard criteria. Offline analysis of digital angiograms was performed in the core laboratory using an automated edge detection system (CMS, Medis Medical Imaging Systems, Neuen, the Netherlands) by personnel blinded to the clinical and CMR data. The initial and post-procedural blood flow in the infarct-related artery was graded according to the TIMI group criteria [23]. In patients with initial angiographic TIMI flow 0–1, the presence of collateral circulation was quantified according to Rentrop et al. [24]. Angiographic analysis included also TIMIframe count (TFC) [25] before and after the procedure and myocardial blush grade (MBG) defined according to the Zwolle group classification [9]. All angiographic data were analyzed by two experienced cardiologists blinded to the clinical and the CMR results. A culprit lesion was described in the presence of an acute occlusion, intraluminal filling defects (or thrombus), ulcerated plaques with contrast-filled pocket protruding into plaque with or without delayed contrast wash-out, extraluminal contrast, dissection or intraluminal flaps [26]. The angiographic presence of coronary thrombus was defined as a filling defect or clearly reduced contrast density or haziness and lesion irregularity, seen in multiple projections surrounded by contrast and in the absence of calcification, which corresponds to an angiographic thrombus burden C1, according to the classification by Sianos et al. [27]. Angiographic criteria for no re-flow were: angiographic evidence of reopening of occluded coronary artery and successful stent placement with no evidence of flowlimiting residual stenosis (\50 %), dissection, spasm, or apparent thrombus and angiographic documentation of a TIMI flow grade B2, or a TIMI flow grade 3 with a TIMI myocardial perfusion grade (TMPG) 0 or 1, at least 10 min after the end of PCI procedure [7].

Biomarker measurements Blood samples for measurements of hs-TnT (normal limit \0.014 ng/ml), creatine kinase-myocardial band (CK-MB; normal limit \24 U/l) and CK (normal limit \170 U/l) were taken on admission and every 8 h for the first 24 h after the procedure and daily thereafter, until discharge. For each of the biomarkers, peak values were defined. Statistical analysis Data are presented as mean ± SD, median [25th–75th percentiles] or counts (%). The normality of distribution of continuous data was tested with the one-sample Kolmogorov–Smirnov test. Continuous data are compared with Student’s t test or Mann–Whitney U test depending on normality of distribution. The correlation between variables was assessed also by calculating the Spearman’s rank correlation coefficient. Categorical variables were compared with the Chi square test or Fischer’s exact test when expected cell values were\5. Multiple logistic regression model was used to identify the independent correlates of MVO. Baseline clinical variable as age, sex, presence of diabetes, angiographic parameters (culprit lesion localization, percentage of stenosis, TIMI flow before and after the procedure, MBG), infarct size at CMR and CK-MB peak value were entered into the model. All analyses were performed using SPSS statistical package (version 20). A 2-sided P \ 0.05 was considered to indicate statistical significance.

Results Baseline data The study included 190 patients with NSTEMI. Mean age was 65.0 ± 9.6 years and 139 patients (73.2 %) were men. MVO was present in 26 patients (13.8 %). Baseline clinical characteristics of patients with and without MVO are shown in Table 1. According to sex, MVO was present in 16.5 % of men (n = 23) and 5.9 % of women (n = 3; P = 0.058). All markers of myocardial necrosis (peak values of hsTnT, CK and CKMB) showed significant differences among patients with and without MVO, showing more extensive myocardial necrosis among patients with MVO. None of the remaining baseline data differed significantly among patients with or without MVO (Table 1). Angiographic data Angiographic data are shown in Table 2. There were significant differences between groups with and without MVO regarding the location of culprit lesion. Of note, in the group

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Int J Cardiovasc Imaging Table 1 Baseline and laboratory data Characteristic

All patients (n = 190)

Patients with MVO (n = 26)

Patients without MVO (n = 164)

P value

Age (years)

65.0 ± 9.6

62.1 ± 11.7

64.4 ± 11.8

Sex, M (%)

139 (73.2)

23(88.5)

116 (70.7)

0.058

Height (cm)

171.5 ± 7.2

172.6 ± 7.9

171.3 ± 8.9

0.28 0.70

0.87

Weight (kg)

81.3 ± 11.4

83.4 ± 13.1

80.9 ± 14.7

Current smoking, n (%)

57 (30)

12 (48)

45 (28)

0.06

Familial history for CAD, n (%)

63 (33)

8 (3)

55 (34)

0.90

Arterial hypertension, n (%) Hypercholesterolemia, n (%)

144 (76) 110 (58)

19 (76) 13 (50)

125 (76) 97 (59)

0.94 0.46

Diabetes mellitus, n (%)

37 (19)

2 (8)

35 (21)

0.12

Requiring insulin, n (%)

9 (5)

1 (4)

8 (5)

0.85

Previous myocardial infarction, n (%)

20 (10)

3 (11.5)

17 (10.36)

0.86

Previous CABG, n (%)

12 (6)

0 (0)

12 (7.3)

0.15

Previous PCI, n (%)

40 (21)

3 (11.5)

37 (22.6)

0.20

LVEF, %

49.5 ± 9.5

47.9 ± 9.6

49.8 ± 9.5

0.63

Peak hs-TnT (ng/ml)

1.86 ± 1.62

4.19 ± 4.85

1.46 ± 1.91

\0.001

Peak CK (U/l)

927.0 ± 666.9

2,262.5 ± 1,242.3

711.27 ± 670.5

\0.001

Peak CKMB (U/l)

124.0 ± 97.4

295.7 ± 191.9

96.3 ± 119.0

\0.001

Data are mean ± SD or number of patients (%) CABG Coronary artery bypass graft, CAD coronary artery disease, CK creatine kinase, CKMB creatine kinase myocardial band, hs-TnT highsensitivity cardiac troponin T, MVO microvascular obstruction, LVEF left ventricle ejection fraction, M males, PCI percutaneous coronary intervention

with MVO, the culprit lesion most commonly resided in the left circumflex artery (17 patients; 65.4 %). The two groups differed also with respect to percentage stenosis, pre-PCI TIMI flow grade, post-PCI TIMI flow grade, MBG, collateral flow, angiographic presence of no-reflow and pre-PCI TIMI frame count (Fig. 1). Pre-PCI TIMI flow grade 0–1 was found in 19 patients in the MVO group and 75 patients in the group without MVO (73.1 vs. 45.7 %; P \ 0.01). MVO group had a lower proportion of patients with post-PCI TIMI flow grade 3 (73.1 vs. 89.6 %; P = 0.011) and a higher proportion of those with MBG 0–1 (54.1 vs. 15.4 %; P \ 0.001) compared with patients without MVO. Of note, in patients with pre-PCI TIMI flow grade 0–1, only one patient (5.3 %) in the group with MVO had angiographic evidence of collateral circulation (defined as Rentrop grade C2) compared with 30 patients (66.6 %) among patients without MVO (P = 0.001). PCI was performed in 181 patients. PCI was not performed in 9 patients because there was no angiographic evidence of significant stenosis. Two of these patients had diffuse slow flow in coronary angiogram. Coronary stents were implanted in 26 patients with MVO and 155 patients without MVO (100 vs. 94.5 %; P = 0.25). CMR data CMR imaging was performed after a median of 4.1 days (3.6–6.9 days) after coronary angiography. MVO was

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detected 26 of 190 patients with CMR late-gadolinium enhancement (LGE) images (13.8 %). In the entire group of patients, median infarct size was 2.1 % (0–6.9 %) of the left ventricle, and there was no evidence of lategadolinium hyperenhanced myocardium in 51 of 190 patients (26.8 %). Patients with MVO had a significantly larger myocardial edema extension which corresponds to the area at risk [23.9 % (17.4–33.9 %) vs. 16.1 % (7.8–27.7 %) of the left ventricle, P = 0.018] and larger infarct size [11.4 % (6.6–19.2 %) vs. 1.4 % (0–4.7 %) of the left ventricle, P \ 0.001; Fig. 2]. Of the nine patients without significant lesions in the angiogram, five underwent T2 mapping and all showed signs of acute myocardial damage. Two patients had myocardial necrosis (1.7 % and 3.1 % of the left ventricle, respectively). However, none of them had MVO. At the time of CMR imaging, patients with MVO had larger left ventricular end-diastolic (187.6 ± 46.2 vs. 146.7 ± 40.2 ml; P = 0.001) and end-systolic (97.6 ± 39.5 vs. 66.8 ± 35.7 ml; P = 0.002) volumes but no differences in the left ventricular ejection fraction (49.9 ± 9.6 vs. 49.8 ± 9.5 %; P = 0.62). The MVO correlated weakly but significantly with the percentage stenosis in the culprit lesion (r = 0.25; P = 0.002) and the initial area at risk (r = 0.24; P = 0.012). We found that all biomarker peak levels were positively correlated with CMR-defined infarct size

Int J Cardiovasc Imaging Table 2 Angiographic data

Characteristic

All patients (n = 190)

Patients with MVO (n = 26)

Patients without MVO (n = 164)

Left main coronary artery

2 (1.1)

0 (0)

2 (1.21)

Left anterior descending coronary artery

69 (36.3)

7 (26.9)

62 (37.8)

Left circumflex coronary artery

53 (27.9)

17 (65.4)

36 (21.9)

Right coronary artery

57 (30.0)

2 (7.7)

55 (33.6)

No significant stenosis

9 (4.7)

0 (0)

9 (5.5)

Vessel size (mm)

2.8 ± 0.4

2.6 ± 0.5

2.8 ± 0.5

0.06

Percentage stenosis

80.5 ± 20.7

93.4 ± 17.6

78.6 ± 27.9

0.002

\0.001

Location of culprit lesion

Angiographic presence of thrombus

102 (53.7)

18 (69.2)

84 (51.2)

0.09

Multivessel disease

118 (62.1)

17 (65.4)

101 (61.6)

0.71

Pre-PCI TIMI flow grade 0

74 (38.9)

17 (65.4)

57 (34.8)

1

20 (10.5)

2 (7.7)

18 (11.0)

2

47 (24.8)

5 (19.2)

42 (25.6)

3

49 (25.8)

2 (7.7)

47 (28.6)

Pre-PCI TIMI frame count

62.1 ± 34.2

77.5 ± 32.8

59.5 ± 35.8

Collateral blood flow (in TIMI 0–1)*

31 (33.0)

1 (5.3)

30 (66.6)

0.001

Post-PCI TIMI flow grade

MVO Microvascular obstruction, PCI percutaneous coronary intervention * Analyzed only in patients with thrombolysis in myocardial infarction (TIMI) flow 0–1

P value

1 (0.5)

0 (0)

1

3 (1.6)

2 (7.7)

1 (0.6)

2

20 (10.5)

5 (19.2)

15 (9.2)

1 (0.6)

3

166 (87.4)

19 (73.1)

147 (89.6)

Post-PCI TIMI frame count

24.31 ± 9.4

28.75 ± 19.2

23.5 ± 14.8

Myocardial blush grade

(n = 167)

(n = 24)

(n = 143)

0

22 (13.2)

8 (33.3)

14 (9.8)

1

13 (7.8)

5 (20.8)

8 (5.6)

2 3

33 (19.7) 99 (59.3)

4 (16.7) 7 (29.2)

29 (20.3) 92 (64.3)

41 (24.4)

14 (58.3)

27 (18.7)

(P \ 0.001) and this correlation was stronger for CKMB (r = 0.420, P \ 0.001). All 51 patients without evidence of myocardial infarction at CMR had biomarkers level above the upper limit of normal: peak TnT 0.757 ± 0.518 ng/ml; peak CK 464.8 ± 259.6 U/l; peak CKMB 71.8 ± 58.0 U/l. Results of the multivariable analysis The multiple logistic regression was used to identify correlates of MVO (see methods for variables entered into the model). The model identified the culprit lesion localization in the circumflex coronary artery [adjusted odds ratio (OR) 13.71, 95 % confidence interval (CI) 2.91–64.58, P \ 0.001) and the infarct size [adjusted OR 3.37 (1.8–6.29), P \ 0.001 for 5 % of the left ventricle increase infarct size) as independent correlates of MVO.

0.001 0.011

0

Angiographic no reflow

0.017

0.13 \0.001

\0.001

Discussion The present study represents the largest series of patients with NSTEMI in whom MVO after early PCI was assessed by CMR imaging. The main findings may be summarized as follow: First, in patients with NSTEMI undergoing early PCI, MVO determined with CMR was a relatively frequent finding being present in 13.8 % of the cases. Second, the localization of the culprit lesion in the left circumflex coronary artery and larger infarct size are independently associated with increased risk for developing MVO after PCI in patients with NSTEMI. Few studies with limited numbers of patients have used CMR imaging to assess MVO in patients with NSTEMI and their results have been controversial [16, 28]. CMR imaging has been used to investigate MVO and infarct size mostly in patients with STEMI undergoing reperfusion with primary PCI or thrombolysis. In these studies the

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Fig. 1 Angiographic characteristics in patients with and without microvascular obstruction (MVO). The left graph proportions of patients with culprit lesion located in the left circumflex artery (LCA); middle graph proportions of patients with angiographic no-reflow; right graph proportions of patients with myocardial blush grade 0–1

Fig. 2 CMR data in patients with and without microvascular obstruction (MVO). Left graph median infarct size (IS), expressed as percentage of the left ventricle. Right graph median extension of initial area at risk, expressed as percentage of the left ventricle

prevalence of MVO varied from 30 to 70 % [14, 15, 29, 30]. The frequency of MVO in patients with NSTEMI found in our study (close to 14 %) is lower than in patients with STEMI. A study by Mewton et al. [16] that included a small number of patients with NSTEMI reported a 32 % frequency of MVO. In an inhomogeneous group of patients with acute coronary syndromes, Hombach et al. [31] reported a 6 % frequency of MVO in patients with NSTEMI. This variability might be primarily explained by the small numbers of patients in these studies. A recent study by Van Assche et al. [32] investigated the relationship between type of infarction (STEMI vs. NSTEMI), IS, transmurality and infarct age in 266 patients (117 patients with NSTEMI). In patients with NSTEMI the prevalence of

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MVO was 31 %, which appears to be higher than the prevalence of MVO in our study. The exact reasons for the observed differences between the studies regarding MVO prevalence in patients with NSTEMI remain unknown. However, both studies concur regarding to the independent association between the MVO extension and IS. The underlying mechanisms of MVO are complex and not completely understood. Animal models of acute myocardial infarction showed that after 140 min of epicardial coronary artery occlusion, endothelial cells become swelled and in association with red cells, platelets and extravascular compression by swelled myocytes and neutrophils would cause the occlusion of capillary bed [33]. Reperfusion itself may also contribute due to potential reperfusion injury by activated neutrophils amplifying the inflammatory response and by distal embolization of atherosclerotic and/or thrombotic material [34, 35]. Actually there is a controversy about the relationship between angiographic status and the MVO. Experimentally induced MVO was initially described only after transient but complete obstruction (TIMI grade 0) of coronary artery [33] and many clinical studies performed in STEMI patients showed a close relationship between the infarct related artery status at baseline and the MVO [18, 36, 37]. At present it is not clear whether the pathogenesis of MVO is the same in STEMI and NSTEMI patients. Only one study that evaluated the MVO in a homogeneous group of patients with NSTEMI showed no significant correlation between the angiographic presentation and MVO [16]. By showing that the lack of tissue reperfusion (blush grade 0–1) and absence of collateral circulation were associated with increased risk of MVO, our findings suggest the existence of similar mechanisms of MVO in NSTEMI and STEMI patients after PCI. In congruence with other studies, we showed that postPCI TIMI flow was not an independent correlate of MVO. In fact, many prior studies have shown that restoration of optimal epicardial blood flow may not result in optimal restoration of reperfusion at tissue level mostly due to MVO [9, 33, 38]. There are several methods for the assessment of microvasculature including MBG [9], ST resolution [39], myocardial contrast echocardiography [11] and CMR [18]. A number of reports had found that MBG provides prognostic information beyond the standard TIMI flow evaluation [9, 10]. In our study MBG was associated with the increased risk of MVO but the association was not statistically independent. Few studies had investigated the association between angiographic and CMR criteria of MVO and their results have been controversial [40, 41]. Husser et al. [15] and Nijvedlt et al. [42] did not show a significant correlation between angiographic MBG and MVO assessed by CMR while in the study of Porto et al. [43] MBG was the only independent predictor of MVO.

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The discrepancy between studies may be explained by the instability of the acute phase, a more dynamic behavior of the microcirculatory system during the first week in patients with acute coronary syndrome [44] and the time gap between early obtained angiographic parameters and CMR parameters obtained on average 1 week later. A second reason could be that the angiographic parameters were not always estimated by a central core laboratory. Time between gadolinium administration and the delayed enhancement imaging may impact on the frequency and/or extension of MVO. It has been reported that high resolution first-pass perfusion CMR detected MVO more frequently and to a greater extent than either early or LGE CMR methods [29, 45]. However, other studies have suggested that hypoenhanced areas that persist at LGE images ([10 min) have the best prognostic impact compared with early first pass and early delayed enhancement images [46, 47] and that persistent late hypoenhanced regions may represent more severely injured myocardium with overt microvascular injury and as such they may be clinically relevant [48, 49]. We observed that patients with MVO had a higher frequency of the left circumflex artery, as culprit vessel, and interestingly this localization was an independent predictor of MVO. This finding is consistent with prior studies that have reported a higher frequency of circumflex coronary artery as culprit vessel in patients with NSTEMI compared with patients with STEMI [50]. Since MVO is seen as an index of the transmurality of myocardial necrosis, this finding may offer another proof for the existence of transmural myocardial necrosis in patients with left circumflex coronary artery involvement despite the lack of respective electrocardiographic criteria, i.e., ST segment elevation. Apart from showing the capacity of MRI to assess the degree of myocardial ischemic damage in patients with NSTEMI, this finding may offer information that narrows differences between NSTEMI and STEMI especially regarding the promptness of application of reperfusion therapy in patients with NSTEMI. The infarct size as found in our study was significantly smaller than infarct size found in patients with STEMI [14], yet it is in line with studies in patients with NSTEMI [16]. Previous studies, involving patients with STEMI have shown a strong association between infarct size and MVO [15, 42, 51]. Our study confirms this finding in patients with NSTEMI and shows that even small infarct size is independently associated with increased risk for MVO. The presence and the extension of MVO also correlate with myocardial area at risk at T2 mapping, but not independently. Current T2 weighted sequences for edema imaging in CMR are limited by low contrast to noise ratios and motion artifacts. During the last years novel CMR imaging techniques for quantification of acute myocardial injury,

particularly the T1-mapping and T2-mapping, have been developed. A recent study that has compared 4 different non-contrast CMR techniques for quantification of acute myocardial injury (area at risk) with the single-photon emission computed tomography (SPECT) has concluded that the novel T2-mapping techniques correlate best with SPECT size with an optimum at a threshold of 60 ms. Moreover, both T1-mapping with MOLLI and T2-weighted turbospin imaging show similar good correlations, but tend to underestimate the defect size [52]. Previous clinical and experimental studies have reported the existence of a relationship between CMR-defined IS and peak serum levels of myocardial necrosis such as cardiac troponin or CKMB [53, 54]. However, this association seems not to be so robust in patients with NSTEMI having a smaller infarct size and lower levels of serum biomarkers [28]. We found a linear correlation between peak levels of biomarkers of myocardial necrosis and CMR-defined infarct size, even though all 51 patients in our series who had no CMR evidence of myocardial infarction had elevated levels of biomarkers of myocardial necrosis. However, after adjustment in the multivariable analysis, CMR-defined IS but not peak levels of hs-TnT or CKMB was independently associated with increased risk of MVO.

Conclusion The present study showed that in NSTEMI patients treated with early PCI, MVO was a frequent finding being present in 13.8 % of the cases. The localization of the culprit lesion in circumflex coronary artery and larger infarct size were independently associated with increased risk for developing MVO in these patients. Conflict of interest

None.

References 1. Avezum A, Makdisse M, Spencer F, Gore JM, Fox KA, Montalescot G et al (2005) Impact of age on management and outcome of acute coronary syndrome: observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 149:67–73 2. Armstrong PW, Fu Y, Chang WC, Topol EJ, Granger CB, Betriu A et al (1998) Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia: the GUSTO-IIb investigators. Circulation 98:1860–1868 3. Ndrepepa G, Mehilli J, Schulz S, Iijima R, Keta D, Byrne RA et al (2009) Patterns of presentation and outcomes of patients with acute coronary syndromes. Cardiology 113:198–206 4. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J et al (1987) Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen

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5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 76:142–154 Investigators G (2001) Rationale and design of the GRACE (Global Registry of Acute Coronary Events) project: a multinational registry of patients hospitalized with acute coronary syndromes. Am Heart J 141:190–199 Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL et al (2000) Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT investigators. Circulation 101:2557–2567 Ndrepepa G, Alger P, Fusaro M, Kufner S, Seyfarth M, Keta D et al (2011) Impact of perfusion restoration at epicardial and tissue levels on markers of myocardial necrosis and clinical outcome of patients with acute myocardial infarction. EuroIntervention 7:128–135 GUSTO Angiographic Investigators (1993) The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 329:1615–1622 van ‘t Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F, Zwolle Myocardial Infarction Study Group (1998) Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Circulation 97:2302–2306 Ndrepepa G, Tiroch K, Fusaro M, Keta D, Seyfarth M, Byrne RA et al (2010) 5-Year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol 55:2383–2389 Ito H, Maruyama A, Iwakura K, Takiuchi S, Masuyama T, Hori M et al (1996) Clinical implications of the ‘no reflow’ phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation 93:223–228 Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J, Mukawa H et al (2000) Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol 36:1202–1209 Bolognese L, Carrabba N, Parodi G, Santoro GM, Buonamici P, Cerisano G et al (2004) Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation 109:1121–1126 Bogaert J, Kalantzi M, Rademakers FE, Dymarkowski S, Janssens S (2007) Determinants and impact of microvascular obstruction in successfully reperfused ST-segment elevation myocardial infarction. Assessment by magnetic resonance imaging. Eur Radiol 17:2572–2580 Husser O, Bodi V, Sanchis J, Nunez J, Lopez-Lereu MP, Monmeneu JV et al (2013) Predictors of cardiovascular magnetic resonance-derived microvascular obstruction on patient admission in STEMI. Int J Cardiol 166:77–84 Mewton N, Bonnefoy E, Revel D, Ovize M, Kirkorian G, Croisille P (2009) Presence and extent of cardiac magnetic resonance microvascular obstruction in reperfused non-ST-elevated myocardial infarction and correlation with infarct size and myocardial enzyme release. Cardiology 113:50–58 Plein S, Greenwood JP, Ridgway JP, Cranny G, Ball SG, Sivananthan MU (2004) Assessment of non-ST-segment elevation acute coronary syndromes with cardiac magnetic resonance imaging. J Am Coll Cardiol 44:2173–2181 Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP et al (1998) Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 97:765–772

123

19. Thiele H, Kappl MJ, Conradi S, Niebauer J, Hambrecht R, Schuler G (2006) Reproducibility of chronic and acute infarct size measurement by delayed enhancement-magnetic resonance imaging. J Am Coll Cardiol 47:1641–1645 20. Friedrich MG, Abdel-Aty H, Taylor A, Schulz-Menger J, Messroghli D, Dietz R (2008) The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol 51:1581–1587 21. Bondarenko O, Beek AM, Hofman MB, Kuhl HP, Twisk JW, van Dockum WG et al (2005) Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J Cardiovasc Magn Reson 7:481–485 22. Hadamitzky M, Langhans B, Hausleiter J, Sonne C, Kastrati A, Martinoff S et al (2013) The assessment of area at risk and myocardial salvage after coronary revascularization in acute myocardial infarction: comparison between CMR and SPECT. JACC Cardiovasc Imaging 6:358–369 23. TIMI Study Group (1985) The thrombolysis in myocardial infarction (TIMI) trial. Phase I findings. N Engl J Med 312:932–936 24. Rentrop KP, Cohen M, Blanke H, Phillips RA (1985) Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 5:587–592 25. Gibson CM, Cannon CP, Daley WL, Dodge JT Jr, Alexander B Jr, Marble SJ et al (1996) TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 93:879–888 26. Kerensky RA, Wade M, Deedwania P, Boden WE, Pepine CJ (2002) Veterans Affairs Non QWISi-HTI. Revisiting the culprit lesion in non-Q-wave myocardial infarction. Results from the VANQWISH trial angiographic core laboratory. J Am Coll Cardiol 39:1456–1463 27. Sianos G, Papafaklis MI, Serruys PW (2010) Angiographic thrombus burden classification in patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention. J Invasive Cardiol 22:6B–14B 28. Giannitsis E, Steen H, Kurz K, Ivandic B, Simon AC, Futterer S et al (2008) Cardiac magnetic resonance imaging study for quantification of infarct size comparing directly serial versus single time-point measurements of cardiac troponin T. J Am Coll Cardiol 51:307–314 29. Hombach V, Grebe O, Merkle N, Waldenmaier S, Hoher M, Kochs M et al (2005) Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 26:549–557 30. Younger JF, Plein S, Barth J, Ridgway JP, Ball SG, Greenwood JP (2007) Troponin-I concentration 72 h after myocardial infarction correlates with infarct size and presence of microvascular obstruction. Heart 93:1547–1551 31. Hombach V, Merkle N, Kestler HA, Torzewski J, Kochs M, Marx N et al (2008) Characterization of patients with acute chest pain using cardiac magnetic resonance imaging. Clin Res Cardiol 97:760–767 32. Van Assche L, Bekkers S, Senthilkumar A, parker MA, Kim AW, Kim RJ (2011) The prevalence of microvascular obstruction in acute myocardial infarction: importance of ST elevation, infarct size, transmurality and infarct age. J Cardiovasc Magn Reson 13(Suppl 1):P147 33. Kloner RA, Ganote CE, Jennings RB (1974) The ‘‘no-reflow’’ phenomenon after temporary coronary occlusion in the dog. J Clin Invest 54:1496–1508 34. Piana RN, Paik GY, Moscucci M, Cohen DJ, Gibson CM, Kugelmass AD et al (1994) Incidence and treatment of ‘no-reflow’

Int J Cardiovasc Imaging

35. 36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

after percutaneous coronary intervention. Circulation 89:2514–2518 Erbel R, Heusch G (2000) Coronary microembolization. J Am Coll Cardiol 36:22–24 Henriques JP, Zijlstra F, Van‘t Hof AW, de Boer MJ, Dambrink JH, Gosselink M et al (2003) Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation 107:2115–2119 Iwakura K, Ito H, Kawano S, Shintani Y, Yamamoto K, Kato A et al (2001) Predictive factors for development of the no-reflow phenomenon in patients with reperfused anterior wall acute myocardial infarction. J Am Coll Cardiol 38:472–477 Lepper W, Hoffmann R, Kamp O, Franke A, de Cock CC, Kuhl HP et al (2000) Assessment of myocardial reperfusion by intravenous myocardial contrast echocardiography and coronary flow reserve after primary percutaneous transluminal coronary angioplasty [correction of angiography] in patients with acute myocardial infarction. Circulation 101:2368–2374 Schroder R, Dissmann R, Bruggemann T, Wegscheider K, Linderer T, Tebbe U et al (1994) Extent of early ST segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction. J Am Coll Cardiol 24:384–391 Sorajja P, Gersh BJ, Costantini C, McLaughlin MG, Zimetbaum P, Cox DA et al (2005) Combined prognostic utility of ST-segment recovery and myocardial blush after primary percutaneous coronary intervention in acute myocardial infarction. Eur Heart J 26:667–674 Baks T, van Geuns RJ, Biagini E, Wielopolski P, Mollet NR, Cademartiri F et al (2005) Recovery of left ventricular function after primary angioplasty for acute myocardial infarction. Eur Heart J 26:1070–1077 Nijveldt R, Beek AM, Hirsch A, Stoel MG, Hofman MB, Umans VA et al (2008) Functional recovery after acute myocardial infarction: comparison between angiography, electrocardiography, and cardiovascular magnetic resonance measures of microvascular injury. J Am Coll Cardiol 52:181–189 Porto I, Burzotta F, Brancati M, Trani C, Lombardo A, Romagnoli E et al (2007) Relation of myocardial blush grade to microvascular perfusion and myocardial infarct size after primary or rescue percutaneous coronary intervention. Am J Cardiol 99:1671–1673 Bodi V, Sanchis J, Lopez-Lereu MP, Nunez J, Sanz R, Palau P et al (2006) Microvascular perfusion 1 week and 6 months after myocardial infarction by first-pass perfusion cardiovascular magnetic resonance imaging. Heart 92:1801–1807 Mather AN, Lockie T, Nagel E, Marber M, Perera D, Redwood S et al (2009) Appearance of microvascular obstruction on high

46.

47.

48.

49.

50.

51.

52.

53.

54.

resolution first-pass perfusion, early and late gadolinium enhancement CMR in patients with acute myocardial infarction. J Cardiovasc Magn Reson 11:33 Wong DT, Leung MC, Richardson JD, Puri R, Bertaso AG, Williams K et al (2012) Cardiac magnetic resonance derived late microvascular obstruction assessment post ST-segment elevation myocardial infarction is the best predictor of left ventricular function: a comparison of angiographic and cardiac magnetic resonance derived measurements. Int J Cardiovasc Imaging 28:1971–1981 Bekkers SC, Backes WH, Kim RJ, Snoep G, Gorgels AP, Passos VL et al (2009) Detection and characteristics of microvascular obstruction in reperfused acute myocardial infarction using an optimized protocol for contrast-enhanced cardiovascular magnetic resonance imaging. Eur Radiol 19:2904–2912 Nijveldt R, Hofman MB, Hirsch A, Beek AM, Umans VA, Algra PR et al (2009) Assessment of microvascular obstruction and prediction of short-term remodeling after acute myocardial infarction: cardiac MR imaging study. Radiology 250:363–370 Lima JA, Judd RM, Bazille A, Schulman SP, Atalar E, Zerhouni EA (1995) Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI: potential mechanisms. Circulation 92:1117–1125 Xu J, Song YB, Hahn JY, Chang SA, Lee SC, Choe YH et al (2012) Comparison of magnetic resonance imaging findings in non-ST-segment elevation versus ST-segment elevation myocardial infarction patients undergoing early invasive intervention. Int J Cardiovasc Imaging 28:1487–1497 Tzivoni D, Koukoui D, Guetta V, Novack L, Cowing G, Investigators CS (2008) Comparison of troponin T to creatine kinase and to radionuclide cardiac imaging infarct size in patients with ST-elevation myocardial infarction undergoing primary angioplasty. Am J Cardiol 101:753–757 Langhans B, Hendrich E, Scho¨mig A, Martinoff S, Hadamitzky H (2013) Reproducibility of area at risk assessment in acute myocardial infarction by T1- and T2-mapping sequences in cardiac magnetic resonance imaging in comparison to Tc99 m-Sestamibi SPECT. J Cardiovasc Magn Reson 15:P240 Chia S, Senatore F, Raffel OC, Lee H, Wackers FJ, Jang IK (2008) Utility of cardiac biomarkers in predicting infarct size, left ventricular function, and clinical outcome after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 1:415–423 Hallen J, Buser P, Schwitter J, Petzelbauer P, Geudelin B, Fagerland MW et al (2009) Relation of cardiac troponin I measurements at 24 and 48 hours to magnetic resonance-determined infarct size in patients with ST-elevation myocardial infarction. Am J Cardiol 104:1472–1477

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Microvascular obstruction in patients with non-ST-elevation myocardial infarction: a contrast-enhanced cardiac magnetic resonance study.

The aim of the study was to assess the frequency and predictive factors of microvascular obstruction (MVO) in patients with non-ST-segment elevation m...
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