http://repub.eur.nl/res/aut/36929/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37657/ 2012-09-18T00:00:00Z 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. http://repub.eur.nl/res/pub/35028/ 2012-01-01T00:00:00Z 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. http://repub.eur.nl/res/pub/28300/ 2010-04-01T00:00:00Z Background: Measuring the rate of clearance of carbon-11 labelled acetate from myocardium using positron emission tomography (PET) is an accepted technique for noninvasively assessing myocardial oxygen consumption. Initial myocardial uptake of [11C]acetate, however, is related to myocardial blood flow (MBF) and several tracer kinetic models for quantifying MBF using [11C]acetate have been proposed. The objective of this study was to assess these models. Methods: Eighteen healthy subjects and 18 patients with hypertrophic cardiomyopathy (HCM) were studied under baseline conditions with [11C]acetate and [15O]water. Four previously reported methods, including single- and multi-tissue compartment models, were used to calculate MBF from the measured [11C]acetate rate of influx K1and the (previously) reported relationship between K1and MBF. These MBF values were then compared with those derived from corresponding [15O]water studies. Results: For all models, correlations between [11C]acetate and [15O]water-derived MBF ranged from .67 to .86 (all P < .005) in the control group and from .73 to .85 (all P < .001) in the HCM group. Two out of four models systematically underestimated perfusion with [11C]acetate, whilst the third model resulted in an overestimation. The fourth model, based on a simple single tissue compartment model with spillover, partial volume and recirculating metabolite corrections, resulted in a regression equation with a slope of near unity and an Y-intercept of almost zero (controls, K1= .74[MBF] 1 .09, r = .86, SEE = .13, P < .001 and HCM, K1= .89[MBF] 1 .03, r = .85, SEE = .12, P < .001). Conclusion: [11C]acetate enables quantification of MBF in fairly good agreement with actual MBF in both healthy individuals and patients with HCM. A single tissue compartment model with standardized correction for recirculating metabolites and with corrections for partial volume and spillover provided the best results. Copyright http://repub.eur.nl/res/pub/28613/ 2010-04-01T00:00:00Z Purpose: Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO2), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). Methods: Twenty patients with HCM (12 men, mean age: 55.2 ± 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 ± 10 years) were studied with [11C]acetate PET to assess MVO2. CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. Results: Between study groups, MVO2(controls: 0.12 ± 0.04 ml•min-1•g-1, HCM: 0.13 ± 0.05 ml•min-1•g-1, p = 0.64) and EW (controls: 9,139 ± 2,484 mmHg•ml, HCM: 9,368 ± 2,907 mmHg•ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 ± 21 g, HCM: 200 ± 76 g, p < 0.001) and MEE was decreased in HCM patients (controls: 35 ± 8%, HCM: 21 ± 10%, p < 0.001). MEE was related to stroke volume (SV), LV outflow tract gradient, NH2-terminal pro-brain natriuretic peptide (NT-proBNP) and serum free fatty acid levels (all p < 0.05). Multivariate analysis revealed that SV ( = 0.74, p < 0.001) and LVM ( = -0.43, p = 0.013) were independently related to MEE. Conclusion: HCM is characterized by unaltered MVO2, impaired EW generation per gram of myocardial tissue and subsequent deteriorated myocardial efficiency. Mechanical external efficiency could independently be predicted by SV and LVM. http://repub.eur.nl/res/pub/26935/ 2009-02-01T00:00:00Z The molecular understanding of diseases has been accelerated in recent years, producing many new potential therapeutic targets. A noninvasive delivery system that can target specific anatomical sites would be a great boost for many therapies, particularly those based on manipulation of gene expression. The use of microbubbles controlled by ultrasound as a method for delivery of drugs or genes to specific tissues is promising. It has been shown by our group and others that ultrasound increases cell membrane permeability and enhances uptake of drugs and genes. One of the important mechanisms is that microbubbles act to focus ultrasound energy by lowering the threshold for ultrasound bioeffects. Therefore, clear understanding of the bioeffects and mechanisms underlying the membrane permeability in the presence of microbubbles and ultrasound is of paramount importance. http://repub.eur.nl/res/pub/30463/ 2008-02-05T00:00:00Z Objective: This study was a pilot trial to determine safety and feasibility of intracoronary infusion of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction (MI). Background: Studies reporting the effect of MBMC therapy on improvement of left ventricular (LV) function have shown variable results. The HEBE trial is a large multicenter, randomized trial that currently enrolls patients. Prior to this trial we performed a pilot study. Methods: Twenty-six patients with a first acute MI were prospectively enrolled in eight centers. Bone marrow aspiration was performed at a median of 6 days after primary PCI (interquartile range, 5-7 days). MBMC were isolated by gradient centrifugation and were infused intracoronary the same day. All patients underwent magnetic resonance imaging before cell infusion and after 4 months. Clinical events were assessed up to 12 months. Results: Within 10 hr after bone marrow aspiration, 246 ± 133 × 106MBMC were infused, of which 3.9 ± 2.3 × 106cells were CD34+. In one patient, this procedure was complicated by local dissection. LV ejection fraction significantly increased from 45.0 ± 6.3% to 47.2 ± 6.5% (P = 0.03). Systolic wall thickening in dysfunctional segments at baseline improved with 0.9 ± 0.7 mm (P < 0.001). Infarct size decreased 37% from 17.8 ± 8.2 to 11.2 ± 4.2 gram (P < 0.001). During 12-month follow-up, 3 additional revascularizations were performed and an ICD was implanted in one patient, 3 weeks after PCI. Conclusion: In patients with acute MI, intracoronary infusion of MBMC is safe in a multicenter setting. At 4-month follow-up, a modest increase in global and regional LV function was observed, with a concomitant decrease in infarct size. http://repub.eur.nl/res/pub/29632/ 2008-02-01T00:00:00Z Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH2-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 ± 0.97 vs. 2.93 ± 0.64 ml·min-1·g-1, P < 0.05). In contrast to controls (1.38 ± 0.15 to 1.25 ± 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 ± 0.11 to 0.88 ± 0.18, P < 0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P < 0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients. Copyright http://repub.eur.nl/res/pub/36259/ 2007-08-01T00:00:00Z Objective: We sought to assess mitral annular (MA) size and function in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) using real-time 3-dimensional (3D) echocardiography (RT3DE). Methods: The study included 30 patients with HCM, 20 patients with DCM, and 30 control subjects. RT3DE measurements included end-systolic and end-diastolic MA area (MAA) (MAA3D), MA diameter3D, MA fractional area change (MAFAC), and MA fractional shortening. In subgroup of 50 patients, magnetic resonance imaging (MRI) was used for MAAMRIand MA diameterMRImeasurement. Results: End-diastolic MAA3Dwas larger in HCM than in control group (P < .0001). Higher MAFAC and MA fractional shortening were present in HCM than in control group (P = .001 and P = .006, respectively). End-systolic and end-diastolic MAA3Din DCM were higher than in HCM and control groups (P < .0001). Lower MAFAC and MA fractional shortening were present in DCM than in HCM and control groups (P < .0001). MAFAC correlated well with left ventricular function in control subjects (r = 0.94, P < .0001), whereas correlation was less in DCM (r = 0.53, P = .02) and HCM (r = 0.42, P < .01). RT3DE and MRI measurements were comparable. Conclusion: RT3DE assessment of MA size and function in control subjects and patients with cardiomyopathy is accurate and well correlated with MRI.