Defining microvascular injury in acute myocardial infarction and response after cell therapy using cardiovascular magnetic resonance imaging

Rossum, A.C. van [Promotor]Beek, A.M. [Copromotor]Nijveldt, R. [Copromotor

Long-term left ventricular remodelling after revascularisation for ST-segment elevation myocardial infarction as assessed by cardiac magnetic resonance imaging

Objective Left ventricular remodelling following a ST-segment elevated myocardial infarction (STEMI) is an adaptive response to maintain the cardiac output despite myocardial tissue loss. Limited studies have evaluated long term ventricular function using cardiac magnetic resonance imaging (CMR) after STEMI. Methods Study population consisted of 155 primary percutaneous coronary intervention treated first STEMI patients. CMR was performed at 4±2 days, 4 months and 24 months follow-up. Patients were treated with beta-blockers, ACE-inhibitors or AT-II-inhibitors, statins and dual antiplatelet according to c

Altered left atrial 4D flow characteristics in patients with paroxysmal atrial fibrillation in the absence of apparent remodeling

The pathophysiology behind thrombus formation in paroxysmal atrial fibrillation (AF) patients is very complex. This can be due to left atrial (LA) flow changes, remodeling, or both. We investigated differences for cardiovascular magnetic resonance (CMR)-derived LA 4D flow and remodeling characteristics between paroxysmal AF patients and patients without cardiac disease. In this proof-of-concept study, the 4D flow data were acquired in 10 patients with paroxysmal AF (age=61 +/- 8 years) and 5 age/gender matched controls (age=56 +/- 1 years) during sinus rhythm. The following LA and LA appendage flow parameters were obtained: flow velocity (mean, peak), stasis defined as the relative volume with velocities<10 cm/s, and kinetic energy (KE). Furthermore, LA global strain values were derived from b-SSFP cine images using dedicated CMR feature-tracking software. Even in sinus rhythm, LA mean and peak flow velocities over the entire cardiac cycle were significantly lower in paroxysmal AF patients compared to controls [(13.12.4 cm/s vs. 16.7 +/- 2.1 cm/s, p=0.01) and (19.3 +/- 4.7 cm/s vs. 26.8 +/- 5.5 cm/s, p=0.02), respectively]. Moreover, paroxysmal AF patients expressed more stasis of blood than controls both in the LA (43.2 +/- 10.8% vs. 27.8 +/- 7.9%, p=0.01) and in the LA appendage (73.3 +/- 5.7% vs. 52.8 +/- 16.2%, p=0.04). With respect to energetics, paroxysmal AF patients demonstrated lower mean and peak KE values (indexed to maximum LA volume) than controls. No significant differences were observed for LA volume, function, and strain parameters between the groups. Global LA flow dynamics in paroxysmal AF patients appear to be impaired including mean/peak flow velocity, stasis fraction, and KE, partly independent of LA remodeling. This pathophysiological flow pattern may be of clinical value to explain the increased incidence of thromboembolic events in paroxysmal AF patients, in the absence of actual AF or LA remodeling.Cardiovascular Aspects of Radiolog

Elevated monocyte-specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon alpha application deteriorates myocardial healing in rats

Monocytes are involved in adverse left ventricular (LV) remodelling following myocardial infarction (MI). To provid

Association of left ventricular flow energetics with remodeling after myocardial infarction: new hemodynamic insights for left ventricular remodeling

Background: Myocardial infarction leads to complex changes in left ventricular (LV) hemodynamics. It remains unknown how four-dimensional acute changes in LV-cavity blood flow kinetic energy affects LV-remodeling.Methods and results: In total, 69 revascularised ST-segment elevation myocardial infarction (STEMI) patients were enrolled. All patients underwent cardiovascular magnetic resonance (CMR) examination within 2 days of the index event and at 3-month. CMR examination included cine, late gadolinium enhancement, and whole-heart four-dimensional flow acquisitions. LV volume-function, infarct size (indexed to body surface area), microvas-cular obstruction, mitral inflow, and blood flow KEi (kinetic energy indexed to end-diastolic volume) charac-teristics were obtained. Adverse LV-remodeling was defined and categorized according to increase in LV end -diastolic volume of at least 10%, 15%, and 20%. Twenty-four patients (35%) developed at least 10%, 17 pa-tients (25%) at least 15%, 11 patients (16%) at least 20% LV-remodeling. Demographics and clinical history were comparable between patients with/without LV-remodeling. In univariable regression-analysis, A-wave KEi was associated with at least 10%, 15%, and 20% LV-remodeling (p = 0.03, p = 0.02, p = 0.02, respectively), whereas infarct size only with at least 10% LV-remodeling (p = 0.02). In multivariable regression-analysis, A-wave KEi was identified as an independent marker for at least 10%, 15%, and 20% LV-remodeling (p = 0.09, p < 0.01, p < 0.01, respectively), yet infarct size only for at least 10% LV-remodeling (p = 0.03).Conclusion: In patients with STEMI, LV hemodynamic assessment by LV blood flow kinetic energetics demon-strates a significant inverse association with adverse LV-remodeling. Late-diastolic LV blood flow kinetic ener-getics early after acute MI was independently associated with adverse LV-remodeling

Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage

AimsLack of gadolinium-contrast wash-in on first-pass perfusion imaging, early gadolinium-enhanced imaging, or late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) imaging after revascularized ST-elevation myocardial infarction (STEMI) is commonly referred to as microvascular obstruction (MVO). Additionally, T2-weighted imaging allows for the visualization of infarct-related oedema and intramyocardial haemorrhage (IMH) within the infarction. However, the exact histopathological correlate of the contrast-devoid core and its relation to IMH is unknown.Methods and resultsIn eight Yorkshire swine, the circumflex coronary artery was occluded for 75 min by a balloon catheter. After 7 days, CMR with cine imaging, T2-weighted turbospinecho, and LGE was performed. Cardiovascular magnetic resonance images were compared with histological findings after phosphotungstic acid-haematoxylin and anti-CD31/haematoxylin staining. These findings were compared with CMR findings in 27 consecutive PCI-treated STEMI patients, using the same scanning protocol. In the porcine model, the infarct core contained extensive necrosis and erythrocyte extravasation, without intact vasculature and hence, no MVO. The surrounding - gadolinium-enhanced - area contained granulation tissue, leucocyte infiltration, and necrosis with morphological intact microvessels containing microthrombi, without erythrocyte extravasation. Areas with IMH (median size 1.92 [0.36-5.25] c

A proinflammatory monocyte response is associated with myocardial injury and impaired functional outcome in patients with ST-segment elevation myocardial infarction: Monocytes and myocardial infarction

Background In patients with ST-segment elevation myocardial infarction (STEMI), the importance of a well-balanced inflammatory reaction has been recognized for years. Monocytes play essential roles in regulating inflammation. Hence, we investigated the association between inflammatory characteristics of monocytes and myocardial injury and functional outcome in patients with STEMI. Methods Using flow cytometry, the levels of classical (CD14(++)CD62L(+)) and nonclassical (CD14(+)CD62L(-)) monocytes were analyzed in peripheral blood in 58 patients with STEMI at a median of 5 days (4-6 days) after primary percutaneous coronary intervention. In addition, the monocytic expression of several surface molecules and formation of monocyte-platelet complexes were measured. All patients underwent cardiovascular magnetic resonance imaging at baseline and 4-month follow-up. Results At baseline, patients with high levels of classical monocytes had impaired left ventricular (LV) ejection fraction (P = .002), larger infarct size (P = .001), and, often, presence of microvascular obstruction (P = .003). At follow-up, high levels of classical monocytes were negatively associated with the regional systolic LV function independent of the transmural extent of infarction. In contrast, positive associations for the levels of nonclassical monocytes were observed. Finally, up-regulation of macrophage 1 by blood monocytes and increased formation of monocyte-platelet complexes were associated with enhanced myocardial injury at baseline and impaired LV function at follow-up. Conclusions This study shows an association between a proinflammatory monocyte response, characterized by high levels of classical monocytes, and severe myocardial injury and poor functional outcome after STEMI. Future studies are required to investigate the biologic nature of this association and therapeutic implications. (Am Heart J 2012;163:57-65.e2.

Doppler-Derived Intracoronary Physiology Indices Predict the Occurrence of Microvascular Injury and Microvascular Perfusion Deficits After Angiographically Successful Primary Percutaneous Coronary Intervention

Background - A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Methods and Results - Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H<inf>2</inf>15O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H<inf>2</inf>15O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). Conclusions - Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow