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.

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).

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.

Late gadolinium-enhanced cardiovascular magnetic resonance evaluation of infarct size and microvascular obstruction in optimally treated patients after acute myocardial infarction.

PURPOSE: Cardiovascular magnetic resonance (CMR) is considered the standard imaging modality in clinical trials to monitor patients after acute myocardial infarction (AMI). However, limited data is available with respect to infarct size, presence, and extent of microvascular injury (MVO), and changes over time, in relation to cardiac function in these optimally treated patients. In this study, we prospectively investigate the change of infarct size over time, and the incidence and significance of MVO in a uniform, optimally treated patient group after AMI. METHODS: Forty patients underwent cine and late gadolinium-enhanced CMR within 9 days and at 4 months after primary stenting. Left ventricular ejection fraction (LVEF), infarct size (IS) and MVO size were calculated. RESULTS: IS decreased with 19.0% at follow-up (p<0.01). The 23 (57.5%) patients with MVO had larger infarct size, higher left ventricular volumes and lower LVEF and more involution of IS at follow-up. Overall, LVEF improved from 42.3+/-9.8% to 44.0+/-9.8% (p=0.06), irrespective of presence or size of MVO. CONCLUSION: Infarct size reduces over time by 19.0% in optimally treated patients after AMI. Despite optimal reperfusion, MVO was found in the majority of patients. Although patients with MVO had larger infarcts and worse indices of left ventricular remodelling, functional change at follow-up was comparable to patients without MVO.

Functional outcome after revascularization in patients with chronic ischemic heart disease: a quantitative late gadolinium enhancement CMR study evaluating transmural scar extent, wall thickness and periprocedural necrosis.

In patients with chronic ischemic myocardial dysfunction, late gadolinium enhancement CMR (LGE-CMR) accurately depicts the regional extent of fibrosis and predicts functional recovery after revascularization. We hypothesized that the predictive accuracy of LGE-CMR could be optimized by not only taking into account the transmural extent of hyperenhancement but also the amount of residual, non-enhanced viable myocardium, and procedure related necrosis. We studied 45 patients with chronic ischemic left ventricular dysfunction, who underwent cine and LGE-CMR 1 month before and 3 months after surgical or percutaneous revascularization. Segmental and global function, scar, presence of a significant residual viable rim (defined as >or=4.5 mm), and procedure related necrosis were fully quantified using standardized methods and objective thresholds. Sixty percent of segments without hyperenhancement showed functional improvement at follow-up. No improvement was observed in segments with >75% segmental extent of hyperenhancement (SEH), while segments with 1-25%, 26-50%, and 51-75% SEH were 4, 8, and 20 times less likely to improve (multilevel analysis, p<0.001). Thickness of the viable rim largely paralleled total wall thickness; therefore, the presence of a significant viable rim did not provide additional diagnostic value beyond SEH. Procedure related necrosis was found in 12 (27%) patients. The presence of procedure related necrosis was the only (negative) predictor of changes in left ventricular volumes and ejection fraction. In conclusion, we found that functional outcome after revascularization was influenced by both transmural extent of hyperenhancement and procedure related necrosis. However, the presence of a significant residual, viable rim was of no additional diagnostic value.

Hyperaemic microvascular resistance is not increased in viable myocardium after chronic myocardial infarction.

AIMS: The present study compared microvascular resistance (MR) of viable myocardium in infarct areas with those in reference areas in patients with chronic myocardial infarction (MI). METHODS AND RESULTS: In 27 patients, MR (ratio distal coronary pressure and flow) of reference and viable infarct areas was calculated at baseline and during hyperaemia. H2 15O positron emission tomography (PET) was used to provide myocardial blood flow measurements. In infarct regions, H2 15O PET solely measures flow in viable myocardium, excluding flow in scar tissue. Distal coronary pressure was measured with a pressure wire in the infarct-related and reference artery. The average time between PET study and infarction was 3.3+/-4.4 years. Mean hyperaemic distal coronary pressure was significantly lower in the infarct-related artery. MR varied considerably between patients and was significantly higher in infarct areas at baseline (135+/-38 vs. 118+/-29 mmHg mL min/mL; P<0.05), but not during hyperaemia (39+/-18 vs. 35+/-11 mmHg mL min/mL). The correlation between MR in infarct and reference areas was significant. CONCLUSION: To determine MR, distal coronary pressure measurements should be used. Hyperaemic MR in viable myocardium within the infarcted area is not higher when compared with the reference area. This supports the application of the established fractional flow reserve cut-off value in the setting of chronic MI.

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.

Effects of stimulation site on diastolic function in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function and clinical status, and prolongs survival of patients suffering from heart failure. An optimal LV site selection is key with respect to improvements in systolic function, though whether a site-specific effect on diastolic function exists is unclear. This study compared the effects of CRT on changes in systolic and diastolic function from 2 LV stimulation sites. METHODS: We studied 21 patients in New York Heart Association functional classes >/= III, and a LV ejection fraction < 0.30 and QRS duration > 130 ms. CRT leads were placed in the right ventricle, right atrium, and coronary sinus tributaries. LV stimulation was applied from the postero-lateral and antero-lateral wall. A LV conductance catheter was used to measure LV systolic and diastolic function. Systolic responders had > 10% changes in dP/dt(max), and diastolic responders < 10% changes in tau during CRT versus baseline. Response was highly dependent on LV lead position for both diastolic and systolic function. Diastolic responders decreased from 29% to 10% of patients, and systolic responders from 76% to 48%, in the best versus the worst lead position, respectively. Improvements in diastolic function were less pronounced than in systolic function (relative change -14% vs +28%, P < 0.05). Overall, 45% were both systolic and diastolic responders, 17% were both systolic and diastolic nonresponders, and 38% had opposite responses. CONCLUSIONS: Changes in systolic and diastolic function were both highly dependent on the LV stimulation site. Diastolic function was less influenced by CRT and a high proportion of patients had discordant results.

New quantitative three-dimensional echocardiographic indices of mitral valve stenosis: new 3D indices of mitral stenosis.

BACKGROUND: We studied the value of quantitative three-dimensional echocardiography (3DE) in the evaluation of mitral valve stenosis using the measurement of the mitral valve area (MVA) with two new indices: the doming volume and mitral valve volume. METHODS AND RESULTS: A total of 45 consecutive patients with mitral valve stenosis were studied. MVA was measured using Doppler with the pressure half-time (PHT) method. Following a diagnostic multiplane transesophageal (TEE) examination, data for 3DE were acquired with a rotational mode of acquisition. MVA was assessed by anyplane echocardiography (APE) and from surface rendered images. Moreover, the doming volume, i.e., the volume subtended by the anterior and posterior mitral valve and annular cut plane was measured by APE. Comparing PHT-derived with 3DE-derived MVA's, using both APE and surface rendered images, only moderate correlations were observed: PHT-derived MVA versus APE-derived MVA: r = 0.74, P < 0.0001; PHT-derived area versus 3DE-surface rendered MVA: r = 0.70, P < 0.0001. Multiple linear regression analysis showed a relation of atrial fibrillation to the doming volume (P = 0.04), but not to PHT-derived MVA (P = 0.28), APE-derived area (P = 0.33) and mitral valve volume (P = 0.08). Comparison of patients with MVA < 1 cm(2) and MVA > 1 cm(2) revealed significant difference in mitral valve volume: mean mitral valve volume in critical stenosis was 3.7 ml versus 1.4 ml in non-critical stenosis (P = 0.04). CONCLUSIONS: Only moderate correlations between 3DE and Doppler-derived MVA's were observed. Measurement of the doming volume allows quantification of the 3DE geometry of the mitral apparatus. Patients with conical or funnel-like geometry are more likely to have sinus rhythm, whereas, patients with flat geometry are likely to have atrial fibrillation. Mitral valve volume can be used for the evaluation of mitral stenosis severity. These new 3DE indices might be used for selection of patients for balloon valvuloplasty.

FDG PET as a predictor of response to resynchronisation therapy in patients with ischaemic cardiomyopathy.

PURPOSE: Although resynchronisation therapy (CRT) is a promising addition to heart failure therapy, a substantial number of patients do not respond to CRT. As FDG PET has routinely been used for prediction of improvement after revascularisation in ischaemic cardiomyopathy, it was hypothesised that there is also a relationship between the extent of viable tissue and improvement as a result of CRT. METHODS: Thirty-nine patients with ischaemic cardiomyopathy (ejection fraction 27 +/- 9%) and a wide QRS complex underwent temporary pacing to determine the optimal pacing combination, i.e. that with the highest increase in cardiac index (CI) compared with baseline (measured by Doppler echocardiography). All patients also underwent FDG PET imaging. In 19 patients, CI measurements were repeated 10-12 weeks after permanent biventricular pacemaker implantation. RESULTS: Echocardiography (13-segment model) showed a mean of 9.8 +/- 1.6 dyssynergic segments, with preserved FDG uptake in 4.1 +/- 2.4 segments. CI improvement at the optimal pacing site was 20 +/- 9%. There was a linear relationship between the extent of viable tissue and CI improvement during pacing (p < 0.001). Using a cut-off value of more than three viable segments (ROC analysis), FDG PET had a sensitivity of 72% and a specificity of 71% for detection of the presence of haemodynamic improvement (i.e. a CI improvement >15%). The relation between CI improvement and viable tissue was similar at follow-up. CONCLUSION: A correlation was found between the extent of viable tissue and the haemodynamic response to CRT in patients with ischaemic cardiomyopathy, suggesting that FDG PET imaging may be useful to discriminate between responders and non-responders to CRT.

Myocardial contrast echocardiography evolving as a clinically feasible technique for accurate, rapid, and safe assessment of myocardial perfusion: the evidence so far.

Intravenous myocardial contrast echocardiography (MCE) is a recently developed technique for assessment of myocardial perfusion. Up to now, many studies have demonstrated that the sensitivity and specificity of qualitative assessment of myocardial perfusion by MCE in patients with acute and chronic ischemic heart disease are comparable with other techniques such as cardiac scintigraphy and dobutamine stress echocardiography. Furthermore, quantitative parameters of myocardial perfusion derived from MCE correlate well with the current clinical standard for this purpose, positron emission tomography. Myocardial contrast echocardiography provides a promising and valuable tool for assessment of myocardial perfusion. Although MCE has been primarily performed for medical research, its implementation in routine clinical care is evolving. This article is intended to give an overview of the current status of MCE.

Septal ablation in hypertrophic obstructive cardiomyopathy improves systolic myocardial function in the lateral (free) wall: a follow-up study using CMR tissue tagging and 3D strain analysis.

AIMS: Alcohol septal ablation (ASA) has been successful in the treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study is to evaluate the effects of ethanol-induced myocardial infarcts on regional myocardial function using cardiac magnetic resonance (CMR) tissue tagging and 3-dimensional (3D) strain analysis. METHODS AND RESULTS: In nine patients (age 52+/-15 years) who underwent ASA, CMR was performed prior to and 6 months after the procedure. Regional myocardial mass was evaluated using cine imaging. Myocardial tagging was used to calculate systolic 3D myocardial strain values. These strain values were used to calculate the shortening index (SI), a robust parameter for myocardial contraction. Maximum end-systolic (ES) SI and systolic SI rate were quantified in three circumferential segments: septum, adjacent, and remote (lateral) myocardium. Compared with baseline, septal and non-septal mass decreased at follow-up (from 72+/-27 to 59+/-21 g; P=0.008 and from 131+/-34 to 109+/-30 g; P=0.008, respectively). In the septum, maximum ES SI and SI rate remained unchanged after ASA. In adjacent myocardium, ES SI remained unchanged, whereas SI rate improved (from -56.5+/-21.1 to -70.0+/-16.7%/s; P=0.02). Both ES SI and SI rate improved significantly in remote myocardium (from -16.9+/-2.8 to -18.8+/-3.2%; P=0.02 and from -70.3+/-9.2 to -86.1+/-15.0%/s; P=0.01, respectively). CONCLUSION: Reduction of left ventricular (LV) outflow tract obstruction in symptomatic HOCM is associated with a significant reduction in myocardial mass and improvement of intramural systolic function in the lateral (remote) wall, indicating reversed LV remodelling.

The diastolic flow velocity-pressure gradient relation and dpv50 to assess the hemodynamic significance of coronary stenoses.

To evaluate the hemodynamic impact of coronary stenoses, the fractional (FFR) or coronary flow velocity reserve (CFVR) usually is measured. The combined measurement of instantaneous flow velocity and pressure gradient (v-dp relation) is rarely used in humans. We derived from the v-dp relation a new index, dp(v50) (pressure gradient at flow velocity of 50 cm/s), and compared the diagnostic performance of dp(v50), CFVR, and FFR. Before coronary angiography was performed, patients underwent noninvasive stress testing. In all coronary vessels with an intermediate or severe stenosis, the flow velocity, aortic, and distal coronary pressure were measured simultaneously with a Doppler and pressure guidewire after induction of hyperemia. After regression analysis of all middiastolic flow velocity and pressure gradient data, the dp(v50) was calculated. With the use of the results of noninvasive stress testing, the dp(v50) cutoff value was established at 22.4 mmHg. In 77 patients, 124 coronary vessels with a mean 39% (SD 19) diameter stenosis were analyzed. In 43 stenoses, ischemia was detected. We found a sensitivity, specificity, and accuracy of 56%, 86%, and 76% for CFVR; 77%, 99%, and 91% for FFR; and 95%, 95%, and 95% for dp(v50). To establish that dp(v50) is not dependent on maximal hyperemia, dp(v50) was recalculated after omission of the highest quartile of flow velocity data, showing a difference of 3%. We found that dp(v50) provided the highest sensitivity and accuracy compared with FFR and CFVR in the assessment of coronary stenoses. In contrast to CFVR and FFR, assessment of dp(v50) is not dependent on maximal hyperemia.

Does myocardial fibrosis hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MR imaging study.

PURPOSE: To prospectively evaluate, by using positron emission tomography (PET) and magnetic resonance (MR) imaging, the interrelationships between regional myocardial fibrosis, perfusion, and contractile function in patients with idiopathic dilated cardiomyopathy (DCM). MATERIALS AND METHODS: The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. Sixteen patients with idiopathic DCM (mean age, 54 years +/- 11 [standard deviation]; nine men) and six healthy control subjects (mean age, 28 years +/- 2; five men) were examined with PET and MR tissue tagging. Oxygen 15-labeled water and carbon monoxide were used as tracers at PET to assess myocardial blood flow (MBF) and the perfusable tissue index (PTI), which is inversely related to fibrosis. MBF was determined at rest and during pharmacologically induced hyperemia. Maximum circumferential shortening (E(cc)) was determined with MR tissue tagging. Student t tests were performed for comparison of data sets, and linear regression was used to investigate the association between parameters. RESULTS: Mean global hyperemic MBF (2.23 mL/min/mL +/- 0.73), E(cc) (-10.5% +/- 2.9), and PTI (0.95 +/- 0.10) were lower in the patients with DCM than in the control subjects (4.33 mL/min/mL +/- 0.85, -17.4% +/- 0.6, and 1.09 +/- 0.12, respectively; P < .05 for all). In the patients with DCM, regional PTI was related to E(cc) (r = -0.21, P = .009) but not to resting or hyperemic MBF. Furthermore, regional E(cc) was correlated to both resting (r = -0.28, P = .004) and hyperemic MBF (r = -0.29, P < .001). In addition, the ratio of left ventricular end-diastolic volume to mass, as a reflection of wall stress, was related to global hyperemic MBF (r = -0.52, P = .047) and to global E(cc) (r = 0.69, P = .003). CONCLUSION: In idiopathic DCM, the extent of myocardial fibrosis is related to the impairment in contractile function, whereas fibrosis and perfusion do not seem to be interrelated. The degree of impairment of hyperemic myocardial perfusion is related to contractility and end-diastolic wall stress.

Glucose-insulin-potassium echocardiography detects improved segmental myocardial function and viable tissue shortly after acute myocardial infarction.

Previous studies showed that glucose-insulin-potassium (GIK) increases cardiac output in patients after cardiac surgery and improves segmental myocardial wall motion. We hypothesized that GIK improves regional wall motion, detects contractile reserve, and predicts functional recovery at follow-up to a similar extent as low-dose dobutamine (LDD) in patients with recent myocardial infarction. Forty-one patients underwent LDD and GIK echocardiography. Data were analyzed according to a 13-segment model. Segments were scored from 0 (normokinesia) to 2 (a-/dyskinesia). Wall motion score index was calculated for baseline and intervention. During GIK, wall motion score index improved from 0.60 +/- 0.25 to 0.39 +/- 0.20 (P < .0001) and from 0.58 +/- 0.25 to 0.39 +/- 0.21 (P < .0001) during LDD. Overall agreement between GIK and LDD echocardiography to detect contractile reserve (improvement of segmental function by >or= 1 point) was 93% with a kappa value of 0.88. Sensitivity, specificity, and positive and negative predictive values of GIK echocardiography to predict functional recovery at follow-up (mean time to follow-up, 13 months) were 74%, 84%, 85%, and 72% respectively, and values were similar to LDD echocardiography. Thus, GIK infusion improves regional left ventricular function and allows the detection of myocardial viability to a similar extent as LDD in patients shortly after infarction.

Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for patients with acute myocardial infarction?

Reperfusion of ischemic myocardium after acute myocardial infarction (AMI) induces a local activation of inflammatory reactions that results in ischemia/reperfusion (I/R)-injury. I/R-injury contributes considerably to the total cell damage in the heart after AMI. Secretory phospolipase A2-IIA (sPLA2-IIA), C-reactive protein (CRP) and complement are inflammatory mediators that have been demonstrated to play key roles in I/R injury. From studies by us and others a mechanism emerged in which sPLA2-IIA binds to reversibly damaged cardiomyocytes and subsequently induces cell death, partly by potentiating binding of CRP and subsequent complement activation. Next to this, sPLA2-IIA also has a direct toxic effect, independent of CRP or complement. Therefore, these studies indicate a crucial role of inflammatory mediators in ischemia/reperfusion injury. This review will focus on the pathogenic effects of sPLA2-IIA, CRP and complement and on the putative therapeutic effects of inhibitors of these inflammatory mediators in acute myocardial infarction.

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.

Quantification of myocardial perfusion using intravenous myocardial contrast echocardiography in healthy volunteers: comparison with positron emission tomography.

BACKGROUND: Intravenous myocardial contrast echocardiography (ivMCE) has the potential to evaluate myocardial contraction and perfusion simultaneously. The purpose of this study was to assess quantification of myocardial blood flow (MBF) using ivMCE and to compare this with MBF as measured with positron emission tomography (PET). METHODS: A total of 16 healthy volunteers underwent ivMCE using power pulse inversion and contrast agent microbubbles at rest and during pharmacologically induced vasodilation. Microbubble destruction was achieved with a burst of high-energy ultrasound, followed by imaging of contrast replenishment with low-energy ultrasound. Regions of interest were drawn and time intensity curves were calculated that were fitted to a monoexponential function. An estimate of MBF (perfusion estime) was calculated as the product of the plateau value A and the exponential beta describing the replenishment curve. MBF was measured with PET using oxygen-15-labeled water at rest and during adenosine stress. RESULTS: Significant correlations were found between MBF as measured with PET and perfusion estimate as measured with ivMCE in the left anterior descending coronary artery (r = 0.87, P < .01), right coronary artery (r = 0.66, P < .01), and left circumflex artery (r = 0.75, P < .01) territories. Heterogeneity, however, was significantly larger for ivMCE (coefficient of variation 32 +/- 15%) than for PET (9 +/- 6%) measurements (P < .01). CONCLUSION: Perfusion parameters as measured with ivMCE correlated with PET-derived MBF, but associated heterogeneity was significantly larger. Currently, this heterogeneity precludes true quantification of MBF using ivMCE.

Measurement of left ventricular volumes and function with O-15-labeled carbon monoxide gated positron emission tomography: comparison with magnetic resonance imaging.

BACKGROUND: Positron emission tomography (PET) with inhaled oxygen 15-labeled carbon monoxide (CO) is used as a marker of myocardial blood pool. Only a limited number of studies with small numbers of patients have reported on the assessment of left ventricular (LV) volumes by use of O-15-labeled CO. The aim of this study was to compare LV volumes and function as measured by routinely acquired blood pool images by use of gated O-15-labeled CO PET with the reference technique, cardiovascular magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty-four subjects with a varying degree of LV function were studied. LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were determined by both MRI and gated PET by use of O-15-labeled CO. Volumes were comparable with respect to LVEDV (196 +/- 83 and 192 +/- 91 mL, respectively; P = not significant). LVESV, however, was slightly overestimated by PET (119 +/- 85 and 136 +/- 94 mL, respectively; P < .05), resulting in a significant underestimation of LVEF (44% +/- 19% and 35% +/- 18%, respectively; P < .05). Observed correlations for LVEDV, LVESV, and LVEF were 0.90, 0.96, and 0.86, respectively (all P < .01). CONCLUSIONS: Gated O-15-labeled CO PET measurements of LVEDV, LVESV, and LVEF show good correlation with MRI over a wide range of LV volumes during routinely acquired blood pool images. LVEF, however, may be underestimated compared with MRI.

Paradoxical embolism due to open foramen ovale with atrial septal aneurysm as a cause of myocardial infarction in a young male.

Paradoxical embolism is a rare cause of myocardial infarction. We present a case of a young man who was admitted to our hospital with an inferior myocardial infarction. Coronary arteriography showed a total distal occlusion of a posterolateral branch of the circumflex artery. Contrast-enhanced echocardiography showed a large atrial septal aneurysm with a patent foramen ovale and massive right-to-left shunting. No other sources of cardiac embolism could be identified. In this case, paradoxical embolism probably has resulted in myocardial infarction.