Lourens Robbers

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

AIMS Lack 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 RESULTS In 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] cm(3)) and MVO (median size 2.19 [0.40-4.58] cm(3)) showed close anatomic correlation [intraclass correlation coefficient (ICC) 0.85, r = 0.85, P = 0.03]. Of the 27 STEMI patients, 15 had IMH (median size 6.60 [2.49-9.79] cm(3)) and 16 had MVO (median size 4.31 [1.05-7.57] cm(3)). Again, IMH and MVO showed close anatomic correlation (ICC 0.87, r = 0.93, P < 0.001). CONCLUSION The contrast-devoid core of revascularized STEMI contains extensive erythrocyte extravasation with microvascular damage. Attenuating the reperfusion-induced haemorrhage may be a novel target in future adjunctive STEMI treatment.

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.

T1 Mapping Shows Increased Extracellular Matrix Size in the Myocardium Due to Amyloid Depositions

Amyloidosis is a systemic infiltrative disorder in which insoluble protein fibrils are deposited in the extracellular matrix (ECM). The prognosis is predominantly determined by cardiac involvement because the amyloid depositions lead to a restrictive cardiomyopathy. Although endomyocardial biopsy is the gold standard for diagnosing cardiac amyloidosis, the associated risk for complications favors a noninvasive approach by using various cardiac imaging methods, whereas tissue diagnosis is made on a noncardiac biopsy. Accurate diagnosis of cardiac amyloidosis becomes difficult when a secondary cause of myocardial wall thickening (eg, hypertension) is present as well. Cardiac MRI is an excellent tool for assessment of systolic and diastolic function, myocardial thickness, and amyloid deposition with late gadolinium enhancement imaging.1 Late gadolinium enhancement imaging is a qualitative technique, which relies on the presence of normal myocardium to visualize infiltrated, enhanced tissue. Therefore, diffuse deposition of amyloid is difficult to highlight, because regional differences in signal intensities may be absent. T1-mapping is a cardiac MR technique, which allows absolute quantification of T1 values of the myocardium and enables assessment of ECM expansion present in cardiac amyloidosis. A 71-year-old man with a medical history of hypertension presented with suspicion of congestive heart failure. A 12-lead electrocardiography showed atrial fibrillation and low voltages in the …

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 H215O 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 H215O 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. Clinical Trial Registration—URL: http://www.trialregister.nl. Unique identifier: NTR3164.

Left ventricular thrombus formation after acute myocardial infarction as assessed by cardiovascular magnetic resonance imaging

INTRODUCTION Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic echocardiography (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the course of LV thrombi in the modern era of primary PCI. METHODS 200 patients with primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24 months for assessment of clinical status and adverse events. RESULTS On CMR at baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus resolution occurred in 15 patients. Two patients had persistence of LV thrombus on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12 patients. In multivariate analysis, thrombus formation on baseline CMR was independently associated with, baseline infarct size (g) (B=0.02, SE=0.02, p<0.001). Routine TTE had a sensitivity of 21-24% and a specificity of 95-98% compared to CMR for the detection of LV thrombi. Intra- and interobserver variation for detection of LV thrombus were lower for CMR (κ=0.91 and κ=0.96) compared to TTE (κ=0.74 and κ=0.53). CONCLUSION LV thrombus still occurs in a substantial amount of patients after PCI-treated MI, especially in larger infarct sizes. Routine TTE had a low sensitivity for the detection of LV thrombi and the interobserver variation of TTE was large.

Myocardial infarct heterogeneity assessment by late gadolinium enhancement cardiovascular magnetic resonance imaging shows predictive value for ventricular arrhythmia development after acute myocardial infarction

AIMS The aim of this study was to assess the association between the proportions of penumbra-visualized by late gadolinium enhanced cardiovascular magnetic resonance imaging (LGE-CMR)-after acute myocardial infarction (AMI) and the prevalence of ventricular tachycardia (VT). METHODS One-hundred and sixty-two AMI patients, successfully, treated by primary percutaneous coronary intervention (PCI) underwent LGE-CMR after a median of 3 days (3-4) and 24-h Holter monitoring after 1 month. With LGE-CMR, the total amount of enhanced myocardium was quantified and divided into an infarct core (>50% of maximal signal intensity) and penumbra (25-50% of maximal signal intensity). With Holter monitoring, the number of VTs (≥4 successive PVCs) per 24 h was measured. RESULTS The mean total enhanced myocardium was 31 ± 11% of the left ventricular mass. The % penumbra accounted for 39 ± 11% of the total enhanced area. In 29 (18%) patients, Holter monitoring showed VT, with a median of 1 episode (1-3) in 24 h. A larger proportion of penumbra within the enhanced area increased the risk of VTs [OR: 1.06 (95% CI: 1.02-1.10), P = 0.003]. After multivariate logistic regression analysis, the presence of ventricular fibrillation before primary PCI [OR: 5.60 (95% CI: 1.54-20.29), P = 0.01] and the proportional amount of penumbra within the enhanced myocardium [OR: 1.06 (95% CI: 1.02-1.10), P = 0.04] were independently associated with VT on Holter monitoring. CONCLUSION Larger proportions of penumbra in the subacute phase after AMI are associated with increased risk of developing VTs. Quantification of penumbra size may become a useful future tool for risk stratification and ultimately for the prevention of ventricular arrhythmias.

Impaired Hyperemic Myocardial Blood Flow Is Associated With Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Background—Risk stratification for ventricular arrhythmias (VAs) is important to refine selection criteria for primary prevention implantable cardioverter defibrillator therapy. Impaired hyperemic myocardial blood flow (MBF) is associated with increased mortality rate in ischemic and nonischemic cardiomyopathy, which may be attributed to electric instability inducing VAs. The aim of this pilot study was to assess whether hyperemic MBF impairment may be related with VA inducibility in patients with ischemic cardiomyopathy. Methods and Results—Thirty patients with ischemic cardiomyopathy referred for primary prevention implantable cardioverter defibrillator implantation were prospectively included (26 men; 65±8 years old; left ventricular ejection fraction, 29±6%). [15O]H2O positron-emission tomography was performed to quantify resting MBF, hyperemic MBF, and coronary flow reserve. Left ventricular dimensions, function, and scar burden were assessed with cardiovascular magnetic resonance imaging. An electrophysiological study was performed to test VA inducibility. Positive electrophysiological study patients (n=12) showed reduced hyperemic MBF (1.25±0.30 versus 1.66±0.38 mL·min−1·g−1; P<0.01) and coronary flow reserve (1.59±0.49 versus 2.12±0.48; P<0.01) compared with electrophysiological study negative patients (n=18). In electrophysiological study positive patients, the number of scar segments >75% transmurality was higher (P<0.05), although scar size and border zone did not differ. Receiver-operating characteristic curve analysis indicated that impaired hyperemic MBF (area under the curve, 0.84; 95% confidence intervals [0.69–0.99]) and coronary flow reserve (area under the curve, 0.77; 95% confidence intervals [0.57–0.96]) were associated with VA inducibility. Conclusions—In this pilot study, impaired hyperemic MBF and coronary flow reserve were associated with VA inducibility in patients with ischemic cardiomyopathy. These results are hypothesis generating for a potential role of quantitative positron-emission tomography perfusion imaging in risk stratification for VAs.

Long term outcome after mononuclear bone marrow or peripheral blood cells infusion after myocardial infarction

Objectives This study reports the long-term follow-up of the randomised controlled HEBE trial. The HEBE study is a multicentre trial that randomised 200 patients with large first acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention to either intracoronary infusion of bone marrow mononuclear cells (BMMCs) (n=69), peripheral blood mononuclear cells (PBMCs) (n=66) or standard therapy (n=65). Methods In addition to 3–5 days, and 4 months after AMI, all patients underwent cardiac MRI after 2 years. A follow-up for 5 years after AMI was performed to assess clinical adverse events, including death, myocardial reinfarction and hospitalisation for heart failure. Results Of the 200 patients enrolled, 9 patients died and 12 patients were lost to follow-up at 5 years after AMI. BMMC group showed less increase in LV end-diastolic volume (LVEDV) (3.5±16.9 mL/m2) compared with (11.2±19.8 mL/m2, p=0.03) in the control group, with no difference between the PBMC group (9.2±20.9 mL/m2) and controls (p=0.69). Moreover, the BMMC group showed a trend for decrease in LV end systolic volume (−1.8±15.0 mL/m2) as compared with controls (3.0±16.3 mL/m2, p=0.07), with again no difference between PBMC (3.3±18.8 mL/m2) and controls (p=0.66). The combined endpoint of death and hospitalisation for heart failure was non-significantly less frequent in the BMMC group compared with the control group (n=4 vs n=1, p=0.20), with no difference between PBMC and controls (n=6 vs n=4, p=0.74). The composite endpoint of death or recurrent myocardial infarction was significantly higher in the PBMC group compared with controls (14 patients vs 3 patients, p=0.008), with no difference between the BMMC group and controls (2 vs 3 patients, p=0.67). Conclusions Long-term follow-up of the HEBE trial showed that increase in LVEDV was lower in the BMMC group. This study supports the long-term safety of intracoronary BMMC therapy. However, major clinical cardiovascular adverse events were significantly more frequent in the PBMC group. Trial registration number The Netherlands Trial Register #NTR166 (http://www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org).

Kinetics of coagulation in ST-elevation myocardial infarction following successful primary percutaneous coronary intervention.

INTRODUCTION ST-elevated myocardial infarction (STEMI) is most frequently caused by coronary occlusion due to formation of an intracoronary thrombus in reaction to rupture of atherosclerotic plaques. Little is known about kinetics of coagulation markers after STEMI in patients treated according to current guidelines. We aimed to investigate kinetics of important coagulation markers in percutaneous coronary intervention (PCI)-treated STEMI patients. MATERIALS AND METHODS 60 consecutive PCI-treated STEMI patients were prospectively included. Blood samples were collected immediately after as well as 1, 4 and 7 days following PCI. Samples collected 90 days after PCI served as baseline values. ADAMTS13 activity, VWF (von Willebrand factor) activity, VWF antigen, VWF propeptide, fibrinogen antigen, D-dimer, alpha2-antiplasmin (α2AP), plasmin-alpha2-antiplasmin complex (PAP), prothrombin fragment F1+2 (F1+2), prothrombin time (PT), activated partial thromboplastin time (aPTT), and anti-factor Xa (anti-Xa) were measured. Cardiac magnetic resonance (CMR) was performed at 4-6 and 90 days after PCI in 49 patients and left ventricular ejection fraction (LVEF), infarct size and microvascular injury (MVI) were determined. RESULTS Immediately after PCI, ADAMTS13 activity, fibrinogen antigen and α2AP levels were significantly decreased and VWF activity, VWF antigen and VWF propeptide levels were significantly elevated, compared to baseline. Individual coagulation markers and different combinations thereof were not related to LVEF or infarct size at 90 days, or the occurrence of MVI at 4-6 days after PCI. CONCLUSION Coagulation parameters show a very dynamic profile in the early days after STEMI. However, individual coagulation parameters or combinations thereof do not predict CMR-defined LVEF, infarct size or MVI.

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 current international guidelines. Results Mean left ventricular ejection fraction (LVEF) at baseline was 44%±8%. Twenty-one per cent of the study population had an increase of more than 5.0% after 4 months of follow-up and 21% of the cohort had a decrease of more than 5.0%. Patients with long-term LVEF deterioration have significantly larger end-systolic volumes than patients with improvement of LVEF (61±23 mL/m2 compared with 52±21 mL/m2, p=0.02) and less wall thickening in the remote zone. Patients with LVEF improvement had significantly greater improvement in wall thickening in the infarct areas and in the non-infarct or remote zone. Conclusion Contrary to previous studies, we demonstrate that myocardial remodelling after STEMI is a long-term process. Long-term LVEF deterioration is characterised by an increase in end-systolic volume and less wall thickening in the remote zones. Patients with LVEF improvement exhibit an increase in left ventricular wall thickening both in the infarct as well as in the remote zones. Trial registration The HEBE study is registered in The Netherlands Trial Register #NTR166 (www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (https://c-d-qn9pqajji.sec.amc.nl).