Time course of functional recovery after revascularization of hibernating myocardium: a contrast-enhanced cardiovascular magnetic resonance study.

AIMS: We sought to evaluate the relation between long-term functional outcome after revascularization in patients with chronic ischaemic left ventricular (LV) dysfunction and baseline extent of myocardial fibrosis. METHODS AND RESULTS: Thirty-five patients underwent cine and delayed contrast-enhanced cardiovascular magnetic resonance (deCMR) for the quantitative assessment of regional and global LV functions and segmental extent of hyperenhancement (SEH). Function was assessed 1 month before and 3, 6, and 24 +/- 12 months after revascularization, and temporal changes were related to baseline extent of hyperenhancement. The likelihood of functional improvement was inversely related to the SEH during the entire follow-up: at the end of the study period, segments with 1-25, 26-50, 51-75, and 76-100% SEH were 2, 5, 11, and 86 times, respectively, less likely to have functional improvement than segments without hyperenhancement (multilevel analysis, P < 0.001). Although improvement continued over the whole study period in all SEH groups, the time course was significantly more delayed in segments with more extensive hyperenhancement at baseline (multilevel analysis, P < 0.001). CONCLUSION: In patients with chronic ischaemic LV dysfunction, improvement of dysfunctional but viable myocardium can be considerably delayed. Both the likelihood and the time course of long-term functional improvement are related to the baseline amount of scar, as visualized by deCMR.

Evaluation of global left ventricular function and mechanical dyssynchrony in patients with an asymptomatic left bundle branch block: a real-time 3D echocardiography study.

BACKGROUND: A left bundle branch block (LBBB) affects both global left ventricular (LV) function and mechanical dyssynchrony. The aim was to evaluate global LV function and mechanical dyssynchrony with real-time 3D echocardiography (RT3DE), in asymptomatic LBBB patients, healthy volunteers and patients with symptomatic heart failure (HF) and a LBBB. Furthermore, the relation between presence or absence of symptoms of HF and mechanical dyssynchrony was investigated. METHODS: RT3DE was performed in 61 consecutive patients: 16 healthy volunteers, 22 patients with an asymptomatic LBBB and 23 patients with symptomatic HF and a LBBB. Global LV function and the systolic dyssynchrony index (SDI) were measured. RESULTS: In healthy volunteers, mean LV ejection fraction was 54 +/- 5%, in asymptomatic LBBB patients 50 +/- 9%, and in HF patients 29 +/- 9%. SDI was 5.6 +/- 3.6%, 7.3 +/- 3.2% and 12.8 +/- 4.8% for healthy volunteers, asymptomatic LBBB patients and HF patients respectively. SDI differed significantly between HF patients and both other groups. A cut-off value for SDI for presence of symptoms of HF was 10.8%. CONCLUSION: Asymptomatic LBBB patients have more depressed global LV function than healthy volunteers have; patients with symptoms of HF and a LBBB have severe global LV dysfunction. Asymptomatic LBBB patients have an intermediate mechanical dyssynchrony; HF patients with a LBBB have the most severe mechanical dyssynchrony. A substantial amount of mechanical dyssynchrony might be accompanied by the presence of symptoms of HF.

Low-intensity ultrasound-exposed microbubbles provoke local hyperpolarization of the cell membrane via activation of BK(Ca) channels.

Ultrasound (US) contrast agents have gained wide interest in gene therapy as many researchers reported increased membrane permeability and transfection efficiency by sonoporation in the presence of US contrast agents. We recently demonstrated an increase in cell membrane permeability for Ca2+ in rat cardiomyoblast (H9c2) cells insonified in the presence of microbubbles. In the present study, we specifically investigated whether US-exposed microbubbles have an effect on the cell membrane potential and whether Ca2+-dependent potassium (BK(Ca)) channels are involved. We particularly focused on local events where the microbubble was in contact with the cell membrane. H9c2 cells were cultured on US transparent membranes. US exposure consisted of bursts with a frequency of 1 MHz with a peak-to-peak pressure of 0.1 or 0.5 MPa. Pulse repetition frequency was set to 20 Hz, with a duty cycle of 0.2%. Cells were insonified during 30 s in the presence of Sonovue(trade mark) microbubbles. The membrane potential was monitored during US exposure using the fluorescent dye di-4-aminonaphtylethenylpyridinium (di-4-ANEPPS). The experiments were repeated in the presence of iberiotoxin (100 nM), a specific inhibitor of BK(Ca) channels. Surprisingly, despite the previously reported Ca(2+) influx, we found patches of hyperpolarization of the cell membrane, as reflected by local increases in di-4-ANEPPS mean intensity of fluorescence (MIF) to 118.6 +/- 2.5% (p < 0.001, n = 267) at 0.1 MPa and 125.7 +/- 5.9% (p < 0.001, n = 161) at 0.5 MPa at t = 74 s, respectively, compared with "no US" (100.3 +/- 3.4%, n = 52). This hyperpolarization was caused by the activation of BK(Ca) channels, as iberiotoxin completely prevented hyperpolarization. (MIF(t74) = 100.6 +/- 1.4%; p < 0.001, n = 267) and 0.5 MPa (MIF(t74) = 88.8 +/- 2.0%; p< 0.001, n = 193), compared with 0.1 and 0.5 MPa microbubbles without iberiotoxin. In conclusion, US-exposed microbubbles elicit a Ca2+ influx, which leads to activation of BK(Ca) channels and a subsequent, local hyperpolarization of the cell membrane. This local hyperpolarization of the cell membrane may facilitate uptake of macromolecules through endocytosis and macropinocytosis. (E-mail: ljm.juffermans@vumc.nl).

Effects of aging on left atrioventricular coupling and left ventricular filling assessed using cardiac magnetic resonance imaging in healthy subjects.

Left ventricular (LV) filling results from diastolic suction of the left ventricle and passive left atrial (LA) emptying at early diastole and LA contraction at end-diastole. Effects of aging on LA and LV geometric characteristics and function and its consequences for LV filling are incompletely understood. Insight into these effects may increase the understanding of diastolic function. Cardiac magnetic resonance imaging was used to study effects of aging on left atrioventricular coupling and LV filling. Forty healthy volunteers underwent cardiac magnetic resonance imaging and were subdivided into 2 age groups of 20 to 40 (younger group) and 40 to 65 years (older group). For the older group, LA volumes were larger (p <0.05) and LV volumes, including stroke volumes, were smaller (p <0.05), whereas ejection fraction remained constant. LA/LV volume ratios were larger (0.27 +/- 0.06 vs 0.19 +/- 0.03; p <0.001) and correlated with LV mass-volume ratio (r = 0.42, p <0.01). The older group also had lower LA passive emptying (15 +/- 3.0 vs 19 +/- 4.8 ml/m(2); p <0.05) and higher LA active emptying volumes (13 +/- 3.1 vs 11 +/- 3.9 ml/m(2); p <0.05). For both groups, conduit volume contributed most to LV filling, but was lower in the older group (21 +/- 5.1 vs 27 +/- 9.0 ml; p <0.05). In conclusion, changes in LA volume and function were age dependent and related to changes in LV mass-volume ratio. Conduit volume contributed most to LV filling and decreased with age, suggesting it to be an indicator of diastolic function.

Early onset and progression of left ventricular remodeling after alcohol septal ablation in hypertrophic obstructive cardiomyopathy.

BACKGROUND: Alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM), which leads to left ventricular remodeling. We sought to describe the early to midterm changes and modulating factors of the remodeling process using cardiac MRI (CMR). METHODS AND RESULTS: CMR was performed at baseline and 1 and 6 months after ASA in 29 patients with HOCM (age 52+/-16 years). Contrast-enhanced CMR showed no infarct-related hyperenhancement outside the target septal area. Septal mass decreased from 75+/-23 g at baseline to 68+/-22 and 58+/-19 g (P<0.001) at 1- and 6-month follow-up, respectively. Remote, nonseptal mass decreased from 141+/-41 to 132+/-40 and 111+/-27 g (P<0.001), respectively. Analysis of temporal trends revealed that septal mass reduction was positively associated with contrast-enhanced infarct size and transmural or left-sided septal infarct location at both 1 and 6 months. Remote mass reduction was associated with infarct location at 6 months but not with contrast-enhanced infarct size. By linear regression analysis, percentage remote mass reduction correlated significantly with LVOT gradient reduction at 6-month follow-up (P=0.03). CONCLUSIONS: Left ventricular remodeling after ASA occurs early and progresses on midterm follow-up, modulated by CMR infarct size and location. Remote mass reduction is associated with infarct location and correlates with reduction of the LVOT pressure gradient. Thus, myocardial hypertrophy in HOCM is, at least in part, afterload dependent and reversible and is not exclusively caused by the genetic disorder.

Impact of scar on water-perfusable tissue index in chronic ischemic heart disease: Evaluation with PET and contrast-enhanced MRI.

BACKGROUND: The water-perfusable tissue index (PTI) is assumed to differentiate viable myocardium from scar tissue, but histological comparisons in humans are lacking. The present study compares PTI with delayed contrast-enhanced magnetic resonance imaging (DCE-MRI), a validated marker of fibrotic tissue, in patients with ischemic left ventricular (LV) dysfunction. In addition, the optimal PTI threshold for detection of myocardial viability was defined when DCE-MRI was taken as a reference. MATERIALS: Twenty patients with ischemic LV dysfunction were studied with positron emission tomography, using oxygen-15-labeled water and carbon monoxide as tracers, and DCE-MRI. RESULTS: Of the 200 analyzed segments, 112 demonstrated DCE and were subsequently divided in three subgroups according to the severity of enhancement. PTI was 1.04 +/- 0.21 in control segments and gradually decreased with increasing extent of DCE to 0.77 +/- 0.31 for segments with transmural enhancement (p < 0.001). However, PTI progressively underestimated infarct size with increasing quantities of scar tissue (r = 0.61, p < 0.01). A PTI cutoff value of 0.89 yielded the best diagnostic accuracy for detection of myocardial viability with sensitivity and specificity values of 75 and 77%, respectively. CONCLUSIONS: PTI is inversely related to the extent of scar tissue estimated by DCE-MRI in patients with chronic ischemic heart disease and LV dysfunction. However, with increasing quantities of scar tissue, PTI overestimates the extent of residual viable tissue. A PTI threshold of 0.89 yields the best diagnostic accuracy for viability detection.

Frame count reserve.

BACKGROUND: The Doppler wire-derived (relative) coronary flow velocity reserve (CVR) that is used to evaluate functional significance of a coronary stenosis is a method performed only by interventional cardiologists. An angiographic method would be useful in the diagnostic catheterization laboratory. For this purpose, we investigated the relation between TIMI frame count reserve (FCR) and CVR. METHODS AND RESULTS: In 38 patients, (relative) FCR of left anterior descending (LAD) and left circumflex coronary artery (LCx) was calculated by using manual, synchronized contrast agent injections and compared with (relative) CVR. In addition, vessel length was measured with an intracoronary guidewire and frame count flow velocity was calculated and compared with average peak velocity. There was a strong correlation between FCR and CVR (r=0.62, P<0.001) and between relative FCR and relative CVR (r=0.84, P<0.001). The LAD was significantly longer than the LCx (mean, 14.3+/-1.6 cm versus 11.4+/-1.8 cm, P<0.001), and, therefore, TIMI frame count of LAD was significantly higher than of LCx (mean basal 32.5+/-15.1 versus 23.6+/-9.1 and hyperemic 12.1+/-6.6 versus 8.7+/-3.2, both P<0.02). However, all flow velocity measurements and estimations of volume flow were not different for LAD compared with LCx. There were also no differences between mean FCR and CVR of LAD or LCx, of both vessels compared with each other and between mean relative FCR and relative CVR. CONCLUSIONS: The (relative) frame count reserve can be used to estimate (relative) coronary flow velocity reserve.

Effects of cardiac resynchronization therapy on myocardial perfusion reserve.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a relatively new treatment strategy for patients with heart failure and mechanical asynchrony. Reported effects of CRT on regional myocardial blood flow (MBF) are conflicting, and effects on hyperemic MBF are scarce. The aim of the present study was to assess serial changes of MBF and MBF reserve in patients receiving a biventricular pacemaker. METHODS AND RESULTS: Fourteen patients with heart failure (NYHA class III or IV; left ventricular ejection fraction <35%), QRS width >120 ms, and sinus rhythm were studied (mean age, 58+/-10 years; 8 men). MBF and hyperemic MBF were measured at baseline, 3 months after biventricular pacing (CRT on), and after cessation of pacing (CRT off) with PET and H2(15)O. CRT had no significant effect on resting MBF (baseline versus CRT on versus CRT off: 0.82+/-0.25 versus 0.69+/-0.24 versus 0.74+/-0.24 mL x min(-1) x mL(-1); P=NS). Hyperemic MBF increased during CRT (1.91+/-1.03 versus 2.66+/-1.66 versus 1.92+/-1.06 mL x min(-1) x mL(-1); P=0.01 by MANOVA), as did MBF reserve (2.25+/-1.00 versus 3.76+/-2.38 versus 2.49+/-0.94 mL x min(-1) x mL(-1); P=0.023). CRT (reversibly) resulted in a more homogeneous distribution of regional resting MBF as demonstrated by the septal-to-lateral ratio. The decrease in the ratio of left ventricular end-diastolic volume to left ventricular mass, as a reflection of wall stress, was related to the increase in hyperemic MBF (r=0.53, P<0.05). Left ventricular ejection fraction increased from 25+/-7% to 37+/-9% (P<0.01). CONCLUSIONS: Resting MBF is unaltered by CRT despite an increase in left ventricular function. However, the distribution pattern of resting MBF becomes more homogeneous. Hyperemic MBF and consequently MBF reserve are enhanced by CRT.

The diastolic flow-pressure gradient relation in coronary stenoses in humans.

OBJECTIVES: We assessed the feasibility and reproducibility of the instantaneous diastolic coronary flow velocity-pressure gradient relation to characterize different degrees of coronary stenoses. BACKGROUND: Assessment of the hemodynamic significance of coronary stenoses can be difficult. Using sensor-tipped guidewires, various physiologic indexes can be determined in the catheterization laboratory. Each of the current methods, however, has limitations. METHODS: After positioning a Doppler flow wire and a pressure wire distal of a coronary stenosis, the flow velocity signals and the proximal and distal pressure were sampled simultaneously, at baseline and after intracoronary administration of adenosine. The instantaneous diastolic flow velocity and pressure gradient of single cardiac cycles at baseline, at maximal and intermediate hyperemia were plotted. Data were fitted with a regression line using the equation: Delta P = 0 +kv+Sv(2). Measurements were performed in 11 normal coronary arteries, 20 intermediate stenoses and in 7 severe stenoses before and after percutaneous transluminal coronary angioplasty plus stenting. RESULTS: We found significant differences between normal coronary arteries, intermediate and severe stenoses. Percutaneous transluminal coronary angioplasty nearly normalized the highly abnormal flow-pressure gradient relation in the severe stenoses. A high degree of reproducibility was observed. In 3% of the measurements, analysis was not possible due to the occurrence of pressure drift or bad flow velocity signals. CONCLUSIONS: It is feasible to assess the diastolic flow velocity-pressure gradient relation over a wide range of stenoses. It characterizes the hemodynamics of epicardial coronary stenoses and allows discrimination between normal coronary arteries, intermediate and severe stenoses.

Delayed contrast-enhanced magnetic resonance imaging for the prediction of regional functional improvement after acute myocardial infarction.

OBJECTIVES: We evaluated whether delayed contrast-enhanced magnetic resonance imaging (DCE-MRI) using an extracellular contrast agent could predict improvement of dysfunctional but viable myocardium after acute reperfused myocardial infarction (MI). BACKGROUND: The transmural extent of hyperenhancement at DCE-MRI has been related to improvement of function in reperfused MI. However, evidence is still limited, and earlier reports have produced conflicting results regarding the significance of contrast patterns after infarction. METHODS: Thirty patients (mean age 59 +/- 11 years, 27 males) underwent cine MRI and DCE-MRI 7 +/- 3 days after a first reperfused acute MI and follow-up cine MRI at 13 +/- 3 weeks. Segmental wall thickening and segmental extent of hyperenhancement were scored in 1,689 segments. RESULTS: Of 500 dysfunctional segments, 273 (55%) improved at follow-up. There was no difference in likelihood of improvement or complete functional recovery between segments with 0% and 1% to 25% hyperenhancement. The likelihood of improvement of segments without hyperenhancement was 2.9, 14.3, and 20 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). The likelihood of complete functional recovery of segments without hyperenhancement was 3.8, 11.1, and 50 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). CONCLUSIONS: In patients with recent reperfused MI, functional improvement of stunned myocardium is predicted by DCE-MRI.

Assessment of coronary artery bypass graft disease using cardiovascular magnetic resonance determination of flow reserve.

OBJECTIVES: The purpose of this study was to assess the value of cardiovascular magnetic resonance (CMR)-determined graft flow and flow reserve in differentiating significant from non-significant vein graft disease. BACKGROUND: In patients after coronary artery bypass grafting (CABG), non-invasive testing may be helpful in the detection of recurrent graft disease. METHODS: Randomly selected patients (n = 21) scheduled for X-ray angiography because of recurrent chest complaints after CABG were included for evaluation of vein grafts (n = 40) by CMR. Three-dimensional contrast-enhanced CMR angiography was performed and followed by flow measurements at rest and during hyperemia in patent grafts only. Flow reserve was calculated when resting flow exceeded 20 ml/min. Analysis was based on four categories defined by X-ray angiography: occluded grafts (n = 3), grafts with stenosis >50% (n = 19), grafts with stenosis <50% with diseased graft run-off (n = 8), and grafts with stenosis <50% and normal run-off (n = 10). RESULTS: The CMR angiography demonstrated occlusion of three grafts. In nine of the 37 patent grafts, basal blood flow was <20 ml/min, all demonstrating significant stenosis at X-ray angiography. In grafts with resting flow >20 ml/min (n = 28), flow reserve significantly differed between grafts without stenosis and grafts with significant stenosis or with diseased run-off (2.5 +/- 0.7 vs. 1.8 +/- 0.9, p = 0.04). An algorithm combining basal volume flow <20 ml/min and graft flow reserve <2 had a sensitivity and specificity of 78% and 80% respectively for detecting grafts with significant stenosis or diseased run-off. CONCLUSIONS: This feasibility study showed that quantification of flow and flow reserve by CMR may serve as a non-invasive adjunct to differentiate between vein grafts without stenosis and grafts with significant stenosis or diseased run-off.

Repeated assessment of coronary flow velocity pattern in patients with first acute myocardial infarction.

OBJECTIVES: The aim of this study was to evaluate the coronary blood flow velocity pattern immediately and 24 h after percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) in relation to myocardial reperfusion and follow-up left ventricular (LV) function. BACKGROUND: Analysis of coronary blood flow velocity pattern after AMI may provide information about microvascular damage and the occurrence of a reperfusion injury. METHODS: Measurement of coronary blood flow velocity pattern was performed immediately after PTCA and after 24 h in 25 patients with first AMI using a Doppler guidewire. Measurements were related to reperfusion determined by intravenous myocardial contrast echocardiography (MCE) performed before PTCA and at 24 h and to LV function at four weeks. RESULTS: Using MCE, 13 patients showed reperfusion and 12 patients showed nonreperfusion. Compared with patients with reperfusion, patients with MCE nonreperfusion had a lower systolic peak flow velocity immediately after PTCA (10.0 +/- 0.3 cm/s vs. 19.3 +/- 0.8 cm/s, respectively) and after 24 h (12.3 +/- 0.4 cm/s vs. 21.3 +/- 0.1 cm/s, respectively, p = 0.0022), more frequent early systolic retrograde flow (6/12 vs. 0/13, p = 0.0052 immediately after PTCA and 24 h later) and a shorter diastolic deceleration time immediately after PTCA (483 +/- 6 ms vs. 737 +/- 0 ms, respectively) and after 24 h (551 +/- 9 ms vs. 823 +/- 2 ms, respectively, p = 0.0091). Similarly, patients with impaired LV function at four weeks had altered coronary flow pattern compared with patients with preserved function. The coronary flow velocity pattern showed a tendency for improvement after 24 h in the reperfusion and the nonreperfusion groups. CONCLUSIONS: The coronary flow velocity pattern immediately and 24 h after PTCA for AMI relates to myocardial perfusion determined by MCE and LV function at four weeks. The flow velocity pattern shows slight improvement during the first 24 h after revascularization, indicating the absence of a major reperfusion injury.

Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponin T.

OBJECTIVES: We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (DSE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T. BACKGROUND: Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain. The prognostic value of immediate DSE has not been studied in a blinded, prospective fashion. METHODS: Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible. Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a standard rule-out protocol and a negative serial troponin T; the occurrence of any new wall motion abnormality was considered positive. Results were kept blinded. End points were cardiac death, myocardial infarction, rehospitalization for unstable angina or revascularization. RESULTS: In total, 377 patients were included. There were 2 deaths, 2 myocardial infarctions, 8 rehospitalization for unstable angina, and 10 revascularizations at six-month follow-up. The end points occurred in 8/26 (30.8%) patients with a positive versus 14/351 (4.0%) patients with a negative DSE (odds ratio, 10.7; 95% confidence interval, 4.0 to 28.8; p < 0.0001). By multivariate analysis, DSE remained a predictor of end points (p < 0.0001). CONCLUSIONS: A predischarge DSE had important, independent prognostic value in low-risk, troponin negative, chest pain patients.

Myocardial infarction after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: evaluation by contrast-enhanced magnetic resonance imaging.

OBJECTIVES: The aim of this study was to evaluate myocardial infarction induced by percutaneous transluminal septal myocardial ablation (PTSMA) in symptomatic patients with hypertrophic obstructive cardiomyopathy using contrast-enhanced (CE) magnetic resonance imaging (MRI). BACKGROUND: Contrast-enhanced MRI delineates the extent of myocardial infarction in coronary artery disease, but its role in ethanol-induced infarction has not been established. METHODS: Cine and CE MRI were performed before and one month after PTSMA in 24 patients. Size and location of the induced infarction were related to left ventricular (LV) mass reduction, enzyme release, volume of ethanol administered, LV outflow tract gradient reduction, and coronary ablation site. RESULTS: One month after PTSMA, regional hyperenhancement was visualized in the basal interventricular septum in all patients. Mean infarction size was 20 +/- 9 g, corresponding to 10 +/- 5% and 31 +/- 16% of total LV and septal mass, respectively. Total LV mass decreased from 219 +/- 64 to 205 +/- 64 g (p < 0.01), and septal mass from 76 +/- 25 to 68 +/- 22 g (p < 0.01). Total LV mass reduction exceeded septal mass reduction (p < 0.01). Infarction size correlated with peak creatine phosphokinase-MB (beta = 0.67, p < 0.01), volume of ethanol administered (beta = 0.47, p = 0.02), total LV and septal mass reduction (beta = 0.50, p = 0.02; beta = 0.73, p < 0.01), and gradient reduction (beta = 0.63, p < 0.01). Seven patients with exclusively right-sided septal infarction had smaller infarction size and less gradient reduction than remaining patients with left-sided or transmural infarction (p < 0.01). In five of these, PTSMA was performed distal in the target artery. CONCLUSIONS: Contrast-enhanced MRI allowed detailed evaluation of size and location of septal myocardial infarction induced by PTSMA. Infarction size correlated well with clinical indexes of infarct size.

Myocardial viability in chronic ischemic heart disease: comparison of contrast-enhanced magnetic resonance imaging with (18)F-fluorodeoxyglucose positron emission tomography.

OBJECTIVES: We sought to compare contrast-enhanced magnetic resonance imaging (ceMRI) with nuclear metabolic imaging for the assessment of myocardial viability in patients with chronic ischemic heart disease and left ventricular (LV) dysfunction. BACKGROUND: Contrast-enhanced MRI has been shown to identify scar tissue in ischemically damaged myocardium. METHODS: Twenty-six patients with chronic coronary artery disease and LV dysfunction (mean ejection fraction 31 +/- 11%) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET), technetium-99m tetrofosmin single-photon emission computed tomography (SPECT), and ceMRI. In a 17-segment model, the segmental extent of hyperenhancement (SEH) by ceMRI, defined as the relative amount of contrast-enhanced tissue per myocardial segment, was compared with segmental FDG and tetrofosmin uptake by PET and SPECT. RESULTS: In severely dysfunctional segments (n = 165), SEH was 9 +/- 14%, 33 +/- 25% (p < 0.05), and 80 +/- 23% (p < 0.05) in segments with normal metabolism/perfusion, metabolism/perfusion mismatch, and matched defects, respectively. Segmental glucose uptake by PET was inversely correlated to SEH (r = -0.86, p < 0.001). By receiver operator characteristic curve analysis, the area under the curve was 0.95 for the differentiation between viable and non-viable segments. At a cutoff value of 37%, SEH optimally differentiated viable from non-viable segments defined by PET. Using this threshold, the sensitivity and specificity of ceMRI to detect non-viable myocardium as defined by PET were 96% and 84%, respectively. CONCLUSIONS: Contrast-enhanced MRI allows assessment of myocardial viability with a high accuracy, compared with FDG-PET, in patients with chronic ischemic heart disease and LV dysfunction.

Delayed contrast enhancement and perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET.

UNLABELLED: Delayed contrast enhancement (DCE) visualized by cardiac MRI (CMR) is a common feature in patients with hypertrophic cardiomyopathy (HCM), presumed to be related to myocardial fibrosis. The pathophysiologic basis of hyperenhancement in this patient group, however, remains unclear as limited histologic comparisons are available. The present study compares the perfusable tissue index (PTI), an alternative marker of myocardial fibrosis obtained by PET, with DCE-CMR in HCM. METHODS: Twenty-one patients with asymmetric septal HCM, 12 chronic myocardial infarction (MI) patients, and 6 age-matched healthy control subjects were studied with DCE-CMR and PET. PET was performed using (15)O-labeled water and carbon monoxide to obtain the PTI. RESULTS: No hyperenhancement was observed in control subjects and the PTI was within normal limits (1.10 +/- 0.07 [mean +/- SD]). In MI patients, the extent of hyperenhancement (25% +/- 16% [mean +/- SD]) was inversely related to the decrease in the PTI (0.94 +/- 0.12; r = -0.65, P < 0.05). Average hyperenhancement in HCM was 14% +/- 12%, predominantly located in the interventricular septum. The PTI in the hypertrophied interventricular septum, however, was not reduced (1.12 +/- 0.13). Furthermore, in contrast to MI patients, there was a modest positive correlation between the extent of DCE and the PTI in HCM (r = 0.45, P < 0.05). CONCLUSION: DCE in the hypertrophied septum of HCM patients is not accompanied by a decline in the PTI, and there is a positive correlation between the extent of DCE and the PTI. These results suggest that hyperenhancement may not be caused solely by fibrotic replacement scarring in this patient group. Other pathologic changes associated with HCM may also cause gadolinium-diethylenetriaminepentaacetic acid hyperenhancement.

Endomyocardial nitric oxide synthase and the hemodynamic phenotypes of human dilated cardiomyopathy and of athlete's heart.

OBJECTIVE: In dilated cardiomyopathy and in athlete's heart, progressive LV dilatation is accompanied by rightward displacement of the diastolic LV pressure-volume relation. In dilated cardiomyopathy, an increase in diastolic LV stiffness can limit this rightward displacement thereby decreasing LV systolic performance. Because nitric oxide (NO) reduces diastolic LV stiffness, the present study relates diastolic LV stiffness and LV systolic performance to intensity of endomyocardial NO synthase (NOS) gene expression in dilated cardiomyopathy and in athlete's heart. METHODS: Microtip LV pressures, conductance-catheter or angiographic LV volumes, echocardiographic LV wall thicknesses and snap-frozen LV endomyocardial biopsies were obtained in 33 patients with dilated cardiomyopathy and in three professional cyclists referred for sustained ventricular tachycardia. Intensity of LV endomyocardial inducible NOS (NOS2) and constitutive NOS (NOS3) gene expression was determined using quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Dilated cardiomyopathy patients with higher diastolic LV stiffness-modulus and lower LV stroke work had lower NOS2 and NOS3 gene expression at any given level of LV end-diastolic wall stress. The intensity of NOS2 and NOS3 gene expression observed in athlete's heart was similar to dilated cardiomyopathy with low LV diastolic stiffness-modulus and preserved LV stroke work. CONCLUSIONS: High LV endomyocardial NOS gene expression is observed in athlete's heart and in dilated cardiomyopathy with low diastolic LV stiffness and preserved LV stroke work. Favourable effects on the hemodynamic phenotype of high LV endomyocardial NOS gene expression could result from a NO-mediated decrease in diastolic LV stiffness and a concomitant rise in LV preload reserve.

Type II secretory phospholipase A2 in cardiovascular disease: a mediator in atherosclerosis and ischemic damage to cardiomyocytes?

Inflammatory reactions contribute to the pathogenesis of cardiovascular conditions such as atherosclerosis and ischemic damage in acute myocardial infarction (AMI). Among the mediators involved in inflammation are secretory phospholipase A2 group II (sPLA2-II) enzymes. Though some cells constitutively express sPLA2-II, the synthesis by cells such as hepatocytes is typical for an acute-phase reactant. Recent literature suggests multiple roles for sPLA2-II in cardiovascular disease. In this review we discuss the role of sPLA2-II in various in vivo and in vitro models of atherosclerosis or AMI, including the therapeutic perspective of sPLA2-II inhibitors. It was concluded that sPLA2-II appears to be an important inflammatory mediator of cardiovascular disease.

Secretory type II phospholipase A(2) binds to ischemic myocardium during myocardial infarction in humans.

OBJECTIVE: An increase of circulating secretory Phospholipase A(2) (sPLA(2)) is a risk factor for coronary artery disease. We hypothesized that this reflects participation of sPLA(2) in local inflammatory reactions ensuing in ischemic myocardium. Therefore, we studied the course of circulating sPLA(2), in patients with acute myocardial infarction (AMI) or unstable angina pectoris (UAP), and investigated the presence of sPLA(2) in infarcted myocardial tissue. METHODS: Plasma samples of 107 patients with AMI or UAP, collected on admission and at varying intervals thereafter, were tested for the presence of sPLA(2) and C-reactive protein (CRP). Cumulative release values of these parameters were calculated, which allowed for comparison of the results rearranged in time according to the onset of symptoms. By immunohistochemistry we studied the presence of sPLA(2) and CRP in myocardial tissue of 30 patients who died subsequent to AMI. RESULTS: Levels of sPLA(2) became elevated during the disease course in 66 of the 87 patients with AMI, and were higher than those of the patients with UAP of whom 8 of the 20 had elevated levels. By immunohistochemistry sPLA(2) was found to be localized in the infarcted myocardium, particularly in its borderzone, from 12 h after the onset of AMI. Positive staining for sPLA(2) was more extensive than that for CRP. CONCLUSIONS: The localization pattern of sPLA(2) in infarcted myocardium as well as its plasma course, in relation to those of CRP, are in line with a supposed pro-inflammatory role during AMI for sPLA(2) as a generator of lysophospholipids serving as ligands for CRP.

Postinjection transmission scanning in myocardial 18F-FDG PET studies using both filtered backprojection and iterative reconstruction.

UNLABELLED: The aim of the present study was to evaluate the effect of postinjection transmission scanning (Post-Tx) on both the qualitative interpretation and the quantitative analysis of cardiac (18)F-FDG PET images. Furthermore, the accuracy of 2 different methods to correct for emission contamination was studied. An additional aim of this study was to compare images reconstructed with both standard filtered backprojection (FBP) and an iterative reconstruction algorithm (ordered-subset maximization expectation [OSEM]). METHODS: Sixteen patients underwent dynamic (18)F-FDG imaging. Both before injection of (18)F-FDG and after completing the emission scan, a 10-min transmission scan was performed (Pre-Tx and Post-Tx, respectively). Images were reconstructed using both FBP and OSEM. The emission study reconstructed with Pre-Tx was considered to be the gold standard. Emission studies were also reconstructed with Post-Tx, with and without correction for emission contamination. Correction for emission contamination was performed with either transmission image segmentation (TIS) or by estimating the emission bias from the last emission frame (dwell profile [DP] method). All images were then compared by calculating ratios of (18)F-FDG activity between corresponding myocardial segments in each patient. Furthermore, qualitative grading of (18)F-FDG uptake was compared between the studies. RESULTS: The mean ratio of (18)F-FDG activity between segments from FBP-Post and FBP-Pre was 0.78 +/- 0.08. When TIS and DP were used, the mean ratios were 0.80 +/- 0.07 and 0.94 +/- 0.06, respectively. The use of OSEM resulted in, on average, 2% lower values for (18)F-FDG activity as compared with FBP. The mean normalized (18)F-FDG uptake was higher in FBP-Post, especially in segments with decreased (18)F-FDG activity. Only in the case of DP were no significant differences observed as compared with FBP-Pre. In general, qualitative analysis of the images showed that the agreement between the reconstruction methods was comparable with the reproducibility of FBP-Pre. CONCLUSION: Post-Tx for attenuation correction in cardiac (18)F-FDG PET scans resulted in substantial underestimation of (18)F-FDG activity. More accurate results were obtained with correction for emission contamination using DP. Differences in visual assessment of (18)F-FDG images were small. Finally, iterative reconstruction could be used as an alternative to FBP in static (18)F-FDG imaging of the heart.