Joey F.A. Ubachs

Myocardium at risk after acute infarction in humans on cardiac magnetic resonance: quantitative assessment during follow-up and validation with single-photon emission computed tomography.

OBJECTIVES Our goal was to validate myocardium at risk on T2-weighted short tau inversion recovery (T2-STIR) cardiac magnetic resonance (CMR) over time, compared with that seen with perfusion single-photon emission computed tomography (SPECT) in patients with ST-segment elevation myocardial infarction, and to assess the amount of salvaged myocardium after 1 week. BACKGROUND To assess reperfusion therapy, it is necessary to determine how much myocardium is salvaged by measuring the final infarct size in relation to the initial myocardium at risk of the left ventricle (LV). METHODS Sixteen patients with first-time ST-segment elevation myocardial infarction received (99m)Tc tetrofosmin before primary percutaneous coronary intervention. SPECT was performed within 4 h and T2-STIR CMR within 1 day, 1 week, 6 weeks, and 6 months. At 1 week, patients were injected with a gadolinium-based contrast agent for quantification of infarct size. RESULTS Myocardium at risk at occlusion on SPECT was 33 +/- 10% of the LV. Myocardium at risk on T2-STIR did not differ from SPECT, at day 1 (29 +/- 7%, p = 0.49) or week 1 (31 +/- 6%, p = 0.16) but declined at week 6 (10 +/- 12%, p = 0.0096 vs. 1 week) and month 6 (4 +/- 11%, p = 0.0013 vs. 1 week). There was a correlation between myocardium at risk demonstrated by T2-STIR at week 1 and myocardium at risk by SPECT (r(2) = 0.70, p < 0.001), and the difference between the methods on Bland-Altman analysis was not significant (-2.3 +/- 5.7%, p = 0.16). Both modalities identified myocardium at risk in the same perfusion territory and in concordance with angiography. Final infarct size was 8 +/- 7%, and salvage was 75 +/- 19% of myocardium at risk. CONCLUSIONS This study demonstrates that T2-STIR performed up to 1 week after reperfusion can accurately determine myocardium at risk as it was before opening of the occluded artery. CMR can also quantify salvaged myocardium as myocardium at risk minus final infarct size.

Cardiovascular magnetic resonance of the myocardium at risk in acute reperfused myocardial infarction: comparison of T2-weighted imaging versus the circumferential endocardial extent of late gadolinium enhancement with transmural projection

BackgroundIn the situation of acute coronary occlusion, the myocardium supplied by the occluded vessel is subject to ischemia and is referred to as the myocardium at risk (MaR). Single photon emission computed tomography has previously been used for quantitative assessment of the MaR. It is, however, associated with considerable logistic challenges for employment in clinical routine. Recently, T2-weighted cardiovascular magnetic resonance (CMR) has been introduced as a new method for assessing MaR several days after the acute event. Furthermore, it has been suggested that the endocardial extent of infarction as assessed by late gadolinium enhanced (LGE) CMR can also be used to quantify the MaR. Hence, we sought to assess the ability of endocardial extent of infarction by LGE CMR to predict MaR as compared to T2-weighted imaging.MethodsThirty-seven patients with early reperfused first-time ST-segment elevation myocardial infarction underwent CMR imaging within the first week after percutaneous coronary intervention. The ability of endocardial extent of infarction by LGE CMR to assess MaR was evaluated using T2-weighted imaging as the reference method.ResultsMaR determined with T2-weighted imaging (34 ± 10%) was significantly higher (p < 0.001) compared to the MaR determined with endocardial extent of infarction (23 ± 12%). There was a weak correlation between the two methods (r2 = 0.17, p = 0.002) with a bias of -11 ± 12%. Myocardial salvage determined with T2-weighted imaging (58 ± 22%) was significantly higher (p < 0.001) compared to myocardial salvage determined with endocardial extent of infarction (45 ± 23%). No MaR could be determined by endocardial extent of infarction in two patients with aborted myocardial infarction.ConclusionsThis study demonstrated that the endocardial extent of infarction as assessed by LGE CMR underestimates MaR in comparison to T2-weighted imaging, especially in patients with early reperfusion and aborted myocardial infarction.

Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

BackgroundPolymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model.MethodsIn anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis.ResultsADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data.ConclusionsADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

Myocardium at risk by magnetic resonance imaging: head-to-head comparison of T2-weighted imaging and contrast-enhanced steady-state free precession.

Aims To determine the myocardial salvage index, the extent of infarction needs to be related to the myocardium at risk (MaR). Thus, the ability to assess both infarct size and MaR is of central clinical and scientific importance. The aim of the present study was to explore the relationship between T2-weighted cardiac magnetic resonance (CMR) and contrast-enhanced steady-state free precession (CE-SSFP) CMR for the determination of MaR in patients with acute myocardial infarction. Methods and results Twenty-one prospectively included patients with first-time ST-elevation myocardial infarction underwent CMR 1 week after primary percutaneous coronary intervention. For the assessment of MaR, T2-weighted images were acquired before and CE-SSFP images were acquired after the injection of a gadolinium-based contrast agent. For the assessment of infarct size, late gadolinium enhancement images were acquired. The MaR by T2-weighted imaging and CE-SSFP was 29 ± 11 and 32 ± 12% of the left ventricle, respectively. Thus, the MaR with T2-weighted imaging was slightly smaller than that by CE-SSFP (−3.0 ± 4.0%; P < 0.01). There was a significant correlation between the two MaR measures (r2= 0.89, P < 0.01), independent of the time after contrast agent administration at which the CE-SSFP was commenced (2–8 min). Conclusion There is a good agreement between the MaR assessed by T2-weighted imaging and that assessed by CE-SSFP in patients with reperfused acute myocardial infarction 1 week after the acute event. Thus, both methods can be used to determine MaR and myocardial salvage at this point in time.

An Improved Method for Automatic Segmentation of the Left Ventricle in Myocardial Perfusion SPECT

This study describes and validates a new method for automatic segmentation of left ventricular mass (LVM) in myocardial perfusion SPECT (MPS) images. This is important for estimating the size of a perfusion defect as percentage of the left ventricle. Methods: A total of 101 patients with known or suspected coronary artery disease underwent both rest and stress MPS and MRI. A new automated algorithm was trained in 20 patients (40 MPS studies) and tested in 81 patients (162 MPS studies). The algorithm, which segmented the left ventricle in the MPS images, is based on Dijkstras algorithm and finds an optimal mid-mural line through the left ventricular wall. From this line, the endocardium and epicardium are identified on the basis of an individually estimated wall thickness and signal intensity. The algorithm was validated by comparing LVM in both stress and rest MPS, with LVM of the manually segmented left ventricle from MRI as the reference standard. For comparison, LVM was quantified using the software quantitative perfusion SPECT (QPS). Results: The mean difference ± SD in LVM between MPS and MRI was lower for the new method (6% ± 15% LVM) than for QPS (18% ± 19% LVM) for both mean difference (P < 0.001) and SD (P = 0.015). Linear regression analysis of LVM, comparing MPS and MRI, yielded R2 = 0.83 using the new method and R2 = 0.80 using QPS. Interstudy variability, measured as the coefficient of variance between rest MPS and stress MPS, was 6% for both the new method and QPS. Both the new algorithm and QPS systematically overestimated LVM in hearts with thin myocardium and underestimated LVM in hearts with thick myocardium. Conclusion: The new segmentation algorithm quantifies LVM with a significantly lower bias and variability than does the commercially available QPS software, when compared to manually segmented LVM by MRI. This makes the new algorithm an attractive method to use for estimating the size of the perfusion defect when expressing it as percentage of the left ventricle. This study shows that inaccurate estimation of wall thickness is the main source of error in automatic segmentation.

The Dipolar ElectroCARdioTOpographic (DECARTO)-like method for graphic presentation of location and extent of area at risk estimated from ST-segment deviations in patients with acute myocardial infarction

A graphic method was developed for presentation of the location and extent of the myocardium at risk in patients with acute myocardial infarction (AMI). This method is based on a mathematical processing of ST-segment deviations of standard 12-lead electrocardiogram following the concept of Titomir and Ruttkay-Nedecky in their dipolar electrocardiotopographic method. The center of the location of the area at risk is given by the spatial orientation of the resultant spatial ST vector, and the extent of the area at risk is derived from the Aldrich score. The areas at risk are projected on a spherical image surface, on which a texture of the anatomical quadrants of the ventricular surface and its coronary artery supply are projected. The method was tested in 10 patients with AMI with single-vessel disease, including 6 patients with an occlusion in the proximal left anterior descending coronary artery (LAD), 3 patients with an occlusion in the right coronary artery, and one patient with occlusion in the left circumflex coronary artery. The estimated areas at risk were compared with myocardial perfusion single photon emission computed tomography. Eight (80%) patients of 10 were correctly localized according to the Aldrich decision rules for the location of AMI. The areas at risk in patients with LAD occlusion correctly localized by the Aldrich score were situated in the anteroseptal and anterosuperior quadrants. In the inferior AMI group, the area at risk was localized in the posterolateral and inferior quadrants. The visual comparison with myocardial perfusion single photon emission computed tomography (SPECT) showed best agreement in patients with LAD involvement. The initial testing showed that this method allows a graphic presentation of estimated area at risk using clinically defined diagnostic rules. The area at risk can be displayed in images that are familiar for clinicians and can be compared with or superimposed on results of other imaging methods used in cardiology.

Semi-automatic segmentation of myocardium at risk in T2-weighted cardiovascular magnetic resonance

BackgroundT2-weighted cardiovascular magnetic resonance (CMR) has been shown to be a promising technique for determination of ischemic myocardium, referred to as myocardium at risk (MaR), after an acute coronary event. Quantification of MaR in T2-weighted CMR has been proposed to be performed by manual delineation or the threshold methods of two standard deviations from remote (2SD), full width half maximum intensity (FWHM) or Otsu. However, manual delineation is subjective and threshold methods have inherent limitations related to threshold definition and lack of a priori information about cardiac anatomy and physiology. Therefore, the aim of this study was to develop an automatic segmentation algorithm for quantification of MaR using anatomical a priori information.MethodsForty-seven patients with first-time acute ST-elevation myocardial infarction underwent T2-weighted CMR within 1 week after admission. Endocardial and epicardial borders of the left ventricle, as well as the hyper enhanced MaR regions were manually delineated by experienced observers and used as reference method. A new automatic segmentation algorithm, called Segment MaR, defines the MaR region as the continuous region most probable of being MaR, by estimating the intensities of normal myocardium and MaR with an expectation maximization algorithm and restricting the MaR region by an a priori model of the maximal extent for the user defined culprit artery. The segmentation by Segment MaR was compared against inter observer variability of manual delineation and the threshold methods of 2SD, FWHM and Otsu.ResultsMaR was 32.9 ± 10.9% of left ventricular mass (LVM) when assessed by the reference observer and 31.0 ± 8.8% of LVM assessed by Segment MaR. The bias and correlation was, -1.9 ± 6.4% of LVM, R = 0.81 (p < 0.001) for Segment MaR, -2.3 ± 4.9%, R = 0.91 (p < 0.001) for inter observer variability of manual delineation, -7.7 ± 11.4%, R = 0.38 (p = 0.008) for 2SD, -21.0 ± 9.9%, R = 0.41 (p = 0.004) for FWHM, and 5.3 ± 9.6%, R = 0.47 (p < 0.001) for Otsu.ConclusionsThere is a good agreement between automatic Segment MaR and manually assessed MaR in T2-weighted CMR. Thus, the proposed algorithm seems to be a promising, objective method for standardized MaR quantification in T2-weighted CMR.

Myocardium at risk can be determined by ex vivo T2-weighted magnetic resonance imaging even in the presence of gadolinium: comparison to myocardial perfusion single photon emission computed tomography

AIMS Determination of the myocardium at risk (MaR) and final infarct size by cardiac magnetic resonance imaging (CMR) enables calculation of salvaged myocardium in acute infarction. T2-weighted imaging is performed prior to the administration of gadolinium, since gadolinium affects T2 tissue properties. This is, however, difficult in an ex vivo model since gadolinium must be administered for determination of infarct size by CMR. We aimed to test the ability of ex vivo T2-weighted imaging to assess MaR using myocardial perfusion single photon emission computed tomography (SPECT) as reference and to investigate whether MaR could be assessed by ex vivo T2-weighted imaging after injection of gadolinium. Materials and methods In 18 domestic pigs, the left anterior descending artery was occluded for either 30 or 40 min, followed by 4 h of reperfusion. After explantation of the hearts, myocardial perfusion SPECT and T2-weighted imaging were performed for determination of MaR, either with or without gadolinium. Infarct size was determined by T1-weighted imaging and by triphenyl tetrazolium chloride (TTC) staining. RESULTS T2-weighted imaging agreed with myocardial perfusion SPECT, both with and without gadolinium (r(2)= 0.70, P < 0.01) with a bias of 2.6 ± 5.1% (P = 0.04). Infarct size was 15.4 ± 5.3 and 22.1 ± 5.6% with TTC and T1-weighted imaging, respectively (P = 0.008) in nine pigs who had both infarct measures. CONCLUSION T2-weighted CMR imaging can be used to determine MaR in an ex vivo experimental model, both with and without the presence of gadolinium. Thus, CMR alone can be used to assess myocardial salvage in experimental studies.

Location of myocardium at risk in patients with first-time ST-elevation infarction: comparison among single photon emission computed tomography, magnetic resonance imaging, and electrocardiography

BACKGROUND The amount of myocardium at risk (MaR) during acute coronary occlusion and the duration of occlusion are important determinants of final infarct size. The main goal of early reperfusion therapy is to salvage ischemic myocardium, thereby preserving left ventricular function. The aims of the present study were to test the feasibility of developing polar plot representations of MaR, for perfusion single photon emission computed tomography (SPECT), regional wall thickening by magnetic resonance imaging (MRI), and distribution of ST-segment changes. A second aim was to test the hypothesis that these different modalities display similar localization of the MaR in patients with reperfused first-time myocardial infarction. METHODS Eleven patients with first-time myocardial infarction with ST-elevation received (99m)Tc tetrofosmin before primary percutaneous coronary intervention, SPECT imaging within 3 hours, and cardiac MRI of the left ventricle within 24 hours. The results for SPECT, MRI, and electrocardiogram (ECG) were developed into polar plots, and two expert observers designated the culprit coronary artery as assessed by angiography. RESULTS The perfusion SPECT, MRI wall thickening, and ST changes are presented in side-by-side polar plots. In total, the culprit artery, based on the location of the MaR, was correctly designated in 91%, 82%, and 91% of cases by SPECT, MRI, and ECG, respectively. CONCLUSIONS Polar representation for localization of the MaR by SPECT perfusion, MRI wall thickening, and ECG ST-segment deviation is feasible. All 3 modalities have the potential to be used for indirect visual designation of the culprit artery in patients with first-time acute coronary occlusion.

Cardiac magnetic resonance for assessment of ST-elevation and non-ST-elevation myocardial infarction.

When a patient shows signs of an acute coronary occlusion, the main goal of treatment is to restore blood flow to the ischemic myocardium to minimize the extent of myocardial infarction. The potential benefit of acute revascularization for cellular and functional recovery, quality of life, and prognosis, might be lost within hours after occlusion since with increasing duration of ischemia, myocardial necrosis will evolve within the ischemic myocardium in a wavefront manner from the endocardial borders of the myocardium towards the epicardium. Current clinical guidelines recommend that patients with signs of acute coronary occlusion undergo percutaneous coronary intervention within 90 minutes. In the acute setting, we still rely on the electrocardiogram to decide whether a patient has to be transported to a hospital capable of performing percutaneous coronary intervention (PCI) (i.e. ST-elevation myocardial infarction). In case of Non-ST-elevation myocardial infarction (NSTEMI), the time delay to reperfusion is often based on the clinical situation and the Global Registry of Acute Coronary Events (GRACE). In the study published in this issue of JECG, Sarafoff et al. report a study to clarify the association of electrocardiographic STEMI and NSTEMI with the size and transmural extent of myocardial necrosis. Two hundred twenty patients with acute myocardial infarction who successfully underwent PCI on the day of admission were studied at 5–7 days by cardiac magnetic resonance imaging (CMR). The contrast enhanced CMR images were assessed for transmural myocardial infarction, based on a 17-segment model. The authors found that the infarct size was significantly larger in STEMI patients compared to NSTEMI patients (25.2 vs. 14.2% of the LV). Furthermore, 63% of the STEMI population and 27% of the NSTEMI population had at least one segment with transmural infarction. This study provides in-vivo confirmation of the pathophysiological differences between different types of acute myocardial infarction, where the infarct size with STEMI is larger than the infarct size by NSTEMI. The study is a welcome addition to what is already known. The population in the current study has a similar sample size as the study by Hombach et al. The results are also in agreement with a study by Plein et al. that STEMI patients had more often transmural infarction. There are some limitations to the study. There are a few important factors influencing the development of necrosis, being the duration of ischemia, preconditioning, collateral flow, and size of the ischemic region. With regards to the duration of ischemia, Sarafoff et al report a time delay of 333 minutes from onset of symptoms to PCI for the STEMI group, whereas for the NSTEMI group this is 635 minutes. Although a significant difference in infarct size was found between the two groups, the presented values of infarct size are not an exact representation of the comparison of the two groups due to the difference in time to reperfusion. Furthermore, there might be an absence of myocardial infarction on the CMR images if early reperfusion is accomplished, referred to as aborted infarction. With regards to the size of the ischemic region, it is generally accepted that NSTEMI represents subendocardial ischemia and STEMI transmural ischemia. Hence, it is to be expected that the ischemic region in STEMI patients represents a larger portion of the left ventricle as compared to NSTEMI patients and therefore have a larger infarct size, depending on the above mentioned factors. Additional data on myocardial ischemia in correlation to infarct size with regards to STEMI and NSTEMI would have been favoured. Thus, as Sarafoff et al. state, it seems that ischemic myocardial injury that results in either ST-elevation or a nonST-elevation pattern seems to be more complex than a simple all or none condition reflecting morphological transmurality.