Robin Nijveldt

Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results.

AbstractDuring the last decennium, the role of bone marrow mononuclear cells (BMMC) has been underscored in the healing process after acute myocardial infarction (AMI). Although these cells improve left ventricular recovery after AMI in experimental studies, results from large-scale randomised trials investigating BMMC therapy in patients with AMI have shown contradictory results. To address this issue the HEBE study was designed, a multicentre, randomised trial, evaluating the effects of intracoronary infusion of BMMCs and the effects of intracoronary infusion of peripheral blood mononuclear cells after primary percutaneous coronary intervention. The primary endpoint of the HEBE trial is the change in regional myocardial function in dysfunctional segments at four months relative to baseline, based on segmental analysis as measured by magnetic resonance imaging. The results from the HEBE trial will provide detailed information about the effects of intracoronary BMMC therapy on post-infarct left ventricular recovery. In addition, further analysis of the data and material obtained may provide important mechanistic insights into the contribution of BMMCs to natural recovery from AMI as well as the response to cell therapy. This may significantly contribute to the development of improved cell-based therapies, aiming at optimising post-infarct recovery and preventing heart failure. (Neth Heart J n2008;16:436-9.)

Early Electrocardiographic Findings and MR Imaging-Verified Microvascular Injury and Myocardial Infarct Size

OBJECTIVESnThis study investigated early electrocardiographic findings in relation to left ventricular (LV) function, extent and size of infarction, and microvascular injury in patients with acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI).nnnBACKGROUNDnThe electrocardiogram (ECG) is the most used and simplest clinical method to evaluate the risk for patients immediately after reperfusion therapy for acute MI. ST-segment resolution and residual ST-segment elevation have been used for prognosis in acute MI, whereas Q waves are related to outcome in chronic MI. We hypothesized that the combination of these electrocardiographic measures early after primary PCI would enhance risk stratification.nnnMETHODSnWe prospectively included 180 patients with a first acute ST-segment elevation MI to assess ST-segment resolution, residual ST-segment elevation, and number of Q waves using the 12-lead ECG acquired on admission and 1 h after successful PCI. The ECG findings were related to LV function, infarction size and transmurality, and microvascular injury as assessed with cine and gadolinium-enhanced cardiac magnetic resonance 4 +/- 2 days after reperfusion therapy.nnnRESULTSnResidual ST-segment elevation (beta = -2.00, p = 0.004) and the number of Q waves (beta = -1.66, p = 0.005) were independent ECG predictors of LV ejection fraction. Although the number of Q waves was the only independent predictor of infarct size (beta = 2.01, p < 0.001) and transmural extent of infarction (beta = 0.60, p < 0.001), residual ST-segment elevation was the only independent predictor of microvascular injury (odds ratio: 19.1, 95% confidence interval: 2.4 to 154, p = 0.005) in multivariable analyses. The ST-segment resolution was neither associated with LV function, infarct size, or transmurality indexes, nor with microvascular injury in multivariable analysis.nnnCONCLUSIONSnIn patients after successful coronary intervention for acute MI, residual ST-segment elevation and the number of Q waves on the post-procedural ECG offer valuable complementary information on prediction of myocardial function and necrosis and its microvascular status.

Pathological Q Waves in Myocardial Infarction in Patients Treated by Primary PCI

OBJECTIVESnIn the present study, we investigated the association of pathological Q waves with infarct size. Furthermore, we investigated whether Q-wave regression was associated with improvement of left ventricular ejection fraction (LVEF), infarct size, and left ventricular dimensions in ST-segment elevation myocardial infarction (STEMI) patients with early Q-wave formation compared with patients without or persistent pathological Q waves.nnnBACKGROUNDnThe criteria for pathological Q waves after acute myocardial infarction (MI) have changed over the years. Also, there are limited data regarding correlation of Q-wave regression and preservation of LVEF in patients with an initial Q-wave MI.nnnMETHODSnStandard 12-lead electrocardiograms (ECGs) were recorded in 184 STEMI patients treated with primary percutaneous coronary intervention (PCI). ECGs were recorded before and following PCI, as well as at 1, 4, 12, and 24 months of follow-up. An ECG was scored as Q-wave MI when it showed Q waves in 2 or more contiguous leads according to the 4 readily available clinical definitions used over the years: classic criteria, Thrombolysis In Myocardial Infarction criteria, and 2000 and 2007 consensus criteria. Cardiac magnetic resonance (CMR) examination was performed at 4 ± 2 days after reperfusion and repeated after 4 and 24 months. Contrast-enhanced CMR was performed at baseline and 4 months.nnnRESULTSnThe classic ECG criteria showed strongest correlation with infarct size as measured by CMR. The incidence of Q-wave MI according to the classic criteria was 23% 1 h after PCI. At 24 months of follow-up, 40% of patients with initial Q-wave MI displayed Q-wave regression. Patients with a Q-wave MI had larger infarct size and lower LVEF on baseline CMR (24 ± 10% LV mass and 37 ± 8%, respectively) compared with patients with non-Q-wave MI (17 ± 9% LV mass, p < 0.01, and 45 ± 8%, p < 0.001, respectively). Patients with Q-wave regression displayed significantly larger LVEF improvement in 24 months (9 ± 11%) as compared with both persistent Q-wave MI (2 ± 8%) as well as non-Q-wave MI (3 ± 8%, p = 0.04 for both comparisons).nnnCONCLUSIONSnAssociation of Q waves with infarct size is strongest when using the classic Q-wave criteria. Q-wave regression is associated with the largest improvement of LVEF as assessed with CMR.

Cell Therapy in Reperfused Acute Myocardial Infarction Does Not Improve the Recovery of Perfusion in the Infarcted Myocardium: A Cardiac MR Imaging Study

PURPOSEnTo investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI).nnnMATERIALS AND METHODSnIn this HEBE trial substudy, which was approved by the institutional review board (trial registry number ISRCTN95796863), the authors assessed the effects of intracoronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test.nnnRESULTSnAt baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P < .001 for all), with equal distribution among treatment groups. These interregional differences persisted at follow-up (P < .001 for all). No difference in perfusion recovery was found between the three treatment groups for any region.nnnCONCLUSIONnAfter revascularization of ST-elevation MI, cell therapy does not augment the recovery of resting perfusion in either the MI core or border zone.

Predictive value of tissue Doppler imaging for left ventricular ejection fraction, remodelling, and infarct size after percutaneous coronary intervention for acute myocardial infarction

AIMSnTo investigate in ST-elevation myocardial infarction (STEMI) patients the value of tissue Doppler imaging (TDI) for an early estimation of the extent of myocardial salvage, left ventricular (LV) remodelling, and residual LV ejection fraction (LVEF).nnnMETHODS AND RESULTSnIn 50 STEMI patients hospitalized for primary percutaneous coronary intervention (PCI), we investigated whether TDI can predict LVEF, infarct size, and LV remodelling as measured by magnetic resonance imaging (MRI) at 4 months post-MI. TDI was assessed within 24 h after MI with colour-coded TDI. Systolic and diastolic velocities from the six basal myocardial segments derived from three standard apical windows were averaged as a measure of global longitudinal velocity (i.e. Sm-6 and Em-6/Am-6, respectively). Sm-6 was shown to be a significant predictor of LVEF at 4 months. In addition, Sm-6 was a significant predictor of infarct size. No significant correlations were found between Sm-6 and LV remodelling. In addition, Sm-6 appeared to be a valuable clinical tool for identification of patients with LVEF > 40% or LVEF < 40% with acceptable positive predictive values.nnnCONCLUSIONnSm-6 is a significant predictor of post-MI LVEF and infarct size as measured by MRI. In contrast, TDI-derived velocities do not predict LV remodelling.

Unsuspected chronic traumatic aortic pseudoaneurysm : what to do about it. Late post-traumatic aortic pseudoaneurysm

A 59-year-old man with multiple risk factors for coronary artery disease who had been in a motor vehicle accident 30 years earlier presented with new-onset angina pectoris. During cardiac catheterization, an ill-defined dense area was noted in the mediastinum. Chest radiography showed an area of calcification around the proximal descending aorta. Cardiovascular magnetic resonance imaging demonstrated a pseudoaneurysm of the proximal descending thoracic aorta. Due to the typical location (aortic isthmus), the pseudoaneurysm was thought to be the result of deceleration injury sustained by the patient in the previous motor vehicle accident. The present manuscript discusses the natural history and management options of an uncommon consequence of traumatic aortic injury: chronic posttraumatic aortic pseudoaneurysm.

The influence of microvascular injury on native T1 and T2* relaxation values after acute myocardial infarction: implications for non-contrast-enhanced infarct assessment

ObjectivesNative T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI). We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI.MethodsForty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE. T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium.ResultsAverage T1 in the MI core was higher than in the MI border zone and remote myocardium. However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02). MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, p<0.001).ConclusionThe presence of MVI profoundly affects MOLLI-measured native T1 values. T2* mapping suggested that this may be the result of intramyocardial haemorrhage. These findings have important implications for the interpretation of native T1 values shortly after AMI.Key points• Microvascular injury after acute myocardial infarction affects local T1 and T2* values.• Infarct zone T1 values are lower if microvascular injury is present.• T2* mapping suggests that low infarct T1 values are likely haemorrhage.• T1 and T2* values are complimentary for correctly assessing post-infarct myocardium.

Value and limitations of electromechanical endocardial mapping in the assessment of global and regional left ventricular function and transmural extent of infarction: a comparison with cardiovascular magnetic resonance.

AIMSnTo determine the relation between electromechanical endocardial mapping (EEM) and cardiac magnetic resonance (CMR) derived functional and viability parameters in patients with a large myocardial infarction.nnnMETHODS AND RESULTSnForty-two patients with a large ST-elevation myocardial infarction underwent both EEM and CMR four months after primary percutaneous coronary intervention. EEM was performed to assess linear local shortening (LLS), unipolar voltage (UV) and bipolar voltage (BV). CMR cine imaging was performed to determine left ventricular global volumes, ejection fraction and regional function. Late gadolinium enhancement was used to assess size and transmural extent of infarction. Average LLS, UV and BV differed significantly between normal and dysfunctional segments (9.8 vs. 7.3, 11.8 vs. 9.7 and 3.3 vs. 2.8 for LLS, UV and BV respectively; p<0.001 for LLS and UV, p=0.006 for BV). In addition, average LLS, UV and BV, differed significantly between non-, subendocardial and transmural enhanced segments (10.8 vs. 8.8 vs. 5.0, 12.3 vs. 10.5 vs. 9.5 and 3.5 vs. 3.0 vs. 2.3 for LLS, UV and BV, respectively, p<0.001 for all variables). Although regional EEM data showed reasonable correlation with CMR, specific cut-off values for EEM parameters could not be established.nnnCONCLUSIONSnEEM may be helpful in determining both the regional function and the transmural extent of infarction in patients with a large myocardial infarction. However, correlation with CMR parameters was moderate and exact cut-off values for EEM parameters could not be established. Further development of this potentially very useful modality is needed before it can be advocated for exact border-zone endocardial injection.

Comparison of strain imaging techniques in CRT candidates: CMR tagging, CMR feature tracking and speckle tracking echocardiography

Parameters using myocardial strain analysis may predict response to cardiac resynchronization therapy (CRT). As the agreement between currently available strain imaging modalities is unknown, three different modalities were compared. Twenty-seven CRT-candidates, prospectively included in the MARC study, underwent cardiac magnetic resonance (CMR) imaging and echocardiographic examination. Left ventricular (LV) circumferential strain was analysed with CMR tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). Basic strain values and parameters of dyssynchrony and discoordination obtained with CMR-FT and STE were compared to CMR-TAG. Agreement of CMR-FT and CMR-TAG was overall fair, while agreement between STE and CMR-TAG was often poor. For both comparisons, agreement on discoordination parameters was highest, followed by dyssynchrony and basic strain parameters. For discoordination parameters, agreement on systolic stretch index was highest, with fair intra-class correlation coefficients (ICC) (CMR-FT: 0.58, STE: 0.55). ICC of septal systolic rebound stretch (SRSsept) was poor (CMR-FT: 0.41, STE: 0.30). Internal stretch factor of septal and lateral wall (ISFsep–lat) showed fair ICC values (CMR-FT: 0.53, STE: 0.46), while the ICC of the total LV (ISFLV) was fair for CMR-FT (0.55) and poor for STE (ICC: 0.32). The CURE index had a fair ICC for both comparisons (CMR-FT: 0.49, STE 0.41). Although comparison of STE to CMR-TAG was limited by methodological differences, agreement between CMR-FT and CMR-TAG was overall higher compared to STE and CMR-TAG. CMR-FT is a potential clinical alternative for CMR-TAG and STE, especially in the detection of discoordination in CRT-candidates.