Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis: is it safe?

To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias (VT, ≥4 successive PVCs) was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control n = 8 vs. BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE.

Semi-automatic measurement of left ventricular function on dual source computed tomography using five different software tools in comparison with magnetic resonance imaging.

PURPOSE: To compare left ventricular (LV) function assessment using five different software tools on the same dual source computed tomography (DSCT) datasets with the results of MRI. MATERIALS AND METHODS: Twenty-six patients, undergoing cardiac contrast-enhanced DSCT were included (20 men, mean age 59±12 years). Reconstructions were made at every 10% of the RR-interval. Function analysis was performed with five different, commercially available workstations. In all software tools, semi-automatic LV function measurements were performed, with manual corrections if necessary. Within 0-22 days, all 26 patients were scanned on a 1.5 T MRI-system. Bland-Altman analysis was performed to calculate limits of agreement between DSCT and MRI. Pearson's correlation coefficient was calculated to assess the correlation between the different DSCT software tools and MRI. Repeated measurements were performed to determine intraobserver and interobserver variability. RESULTS: For all five DSCT workstations, mean LV functional parameters correlated well with measurements on MRI. Bland-Altman analysis of the comparison of DSCT and MRI showed acceptable limits of agreement. Best correlation and limits of agreement were obtained by DSCT software tools with software algorithms comparable to MRI software. CONCLUSION: The five different DSCT software tools we examined have interchangeable results of LV functional parameters compared to regularly analysed results by MRI. The best correlation and the narrowest limits of agreement were found when the same software algorithm was used for both DSCT and MRI examinations, therefore our advice for clinical practice is to always evaluate images with the same type of post-processing tools in follow-up.

Evaluation of global left ventricular function assessment of non-fluorescent electromechanical endocardial mapping compared with biplane left ventricular contrast angiography.

Background. Little is known about the diagnostic accuracy of global LV function assessment by electromechanical endocardial mapping (EEM). The aim of the present study was to determine the relationship between global left ventricular (LV) function measured by EEM and biplane left ventricular contrast angiography (LVA) after ST-elevation myocardial infarction (STEMI).Methods. Thirty-seven patients underwent LVA and EEM during routine coronary angiography four months after primary percutaneous intervention for STEMI. Global LV function parameters were available from both techniques in all patients. LVA was regarded as reference standard.Results. All procedures were carried out without adverse events. Average age was 55+/-10 years and 84% were male. EEM showed an overestimation of end-diastolic volume (EDV) and end-systolic volume (ESV) of 6.5 ml and 25.5 ml, respectively. Correlation (r) was 0.84 (p<0.001) for EDV and 0.74 (p<0.001) for ESV. Average left ventricular ejection fraction (LVEF) measured by EEM was 17.2% point (+/-11.3% point) lower compared with LVA (r=0.69, p<0.001).Conclusion. Although global functional parameters by EEM correlated well with LVA, the relatively large differences in terms of absolute values for ventricular volumes and LVEF render the two techniques non-interchangeable for global LV-function-data. (Neth Heart J 2010;18:72-77.).

Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. beta-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance. METHODS: Patients with newly diagnosed IDC underwent Positron Emission Tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dipyridamole stress), and (18)F-fluoro-deoxyglucose as a metabolism tracer, and a dobutamine stress MRI. MRI and PET were repeated 6 months after maximal beta-blocker therapy. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17 segment-model. Functional response to beta-blocker therapy was assigned as a stable or improved LVEF or diminished LVEF. RESULTS: Sixteen patients were included (age 47.9 +/- 11.5 years; 12 males, LVEF 28.6 +/- 8.4%). Seven patients showed improved LVEF (9.7 +/- 3.1%), and nine patients did not show improved LVEF (-3.4 +/- 3.9%). MPR improved significantly in responders (1.56 +/- .23 to 1.93 +/- .49, P = .049), and MPR decreased in non-responders; however, not significantly (1.98 +/- .70 to 1.61 +/- .28, P = .064), but was significantly different between both groups (P = .017) after beta-blocker therapy. A significant correlation was found between change in perfusion reserve and change in LVEF: a decrease in perfusion reserve was associated with a decrease in LVEF and vice versa. Summed rest score of wall motion in responders improved from 26 to 21 (P = .022) whereas in non-responders no change was observed from 26 to 25) (P = ns). Summed stress score of wall motion in responders improved from 23 to 21 (P = .027) whereas in non-responders no change was observed from 27 to 26) (P = ns). CONCLUSION: In IDC patients, global as well as regional improvement after initiation of beta-blocker treatment is accompanied by an improvement in regional perfusion parameters. On the other hand in IDC patients with further left ventricular function deterioration after initiation of beta-blocker therapy this is accompanied by a decrease in perfusion reserve.

The reliability of automatic measurement of left ventricular function with dual-source computed tomography datasets.

The purpose of the study was to assess the reliability of (semi-) automatic left ventricular (LV) function measurements using three different software packages on the same dual-source computed tomography (DSCT) datasets and to compare agreement among the software packages. Forty consecutive patients, undergoing cardiac DSCT were included (31 men, mean age 58±14 years). LV function analysis was performed with all three software packages. ANOVA testing was used to determine the difference among the repeated measurements and the difference among the software packages. Bland-Altman plots were computed to describe the agreement among the software packages. No significant difference was found among the repeated measurements. In the comparison of the three software packages, a significant difference was observed when measurements were used with minimal user interaction. When end-diastolic and end-systolic phases were manually set, there was no overall significant difference, but in 12.5% of patients a large (>10%) difference in LVEF was found. All three software packages have good intraobserver variability, but the results of the three packages were significantly different. For clinical use, one should be aware of the clinical impact of possible segmentation flaws when (semi-)automatic LV function assessment is used.

Incidence, predictors, and outcome of reinfarction and stent thrombosis within one year after primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Reinfarction and stent thrombosis are major complications after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). OBJECTIVE: We sought to investigate the incidence, predictors, and outcome of reinfarction and stent thrombosis in a contemporary cohort of STEMI patients. METHODS: Reinfarction and stent thrombosis within 1 year after primary PCI for STEMI were analyzed in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS). RESULTS: Reinfarction was observed in 3.4% (34/995) of patients within 1 year after primary PCI. Angiographic evidence of stent thrombosis was observed in 15/34 (44.1%). During the index primary PCI, intra-aortic balloon counterpulsation was used in 10/32 (31.3%) patients with and 47/900 (5.2%) without reinfarction (P < 0.001). After the index primary PCI, thrombus was visible in 6/34 (17.7%) with reinfarction when compared with that in 25/952 (2.6%) without reinfarction (P < 0.001), and complete ST-segment resolution in 8/33 (24.2%) compared with that in 462/892 (51.8%, P = 0.002). Mortality at 1 year after the index PCI was higher after reinfarction: 6/34 (17.7%) compared with 53/961 (5.5%, P = 0.003). Patients with stent thrombosis showed myocardial blush grade 0-1 in 11/15 (73.3%) cases, distal embolization in 8/15 (53.3%), and a mortality at 1 year of 4/15 (26.7%). CONCLUSIONS: In contemporary practice with primary PCI and triple antiplatelet therapy for STEMI, the incidence of reinfarction is low. Outcome characteristics after the index PCI were important determinants of reinfarction. However, reinfarction was associated with poor prognosis, and in particular patients with stent thrombosis had poor outcome.

Comparison of MRI, 64-slice MDCT and DSCT in assessing functional cardiac parameters of a moving heart phantom.

To compare magnetic resonance imaging (MRI), 64-slice multi-detector computed tomography (MDCT) and dual-source computed tomography (DSCT) in assessing global function parameters using a moving heart phantom. A moving heart phantom with known volumes (215-258 ml) moving at 50-100 beats per minute was examined by three different imaging modalities using clinically implemented scanning protocols. End-diastolic and end-systolic volumes were calculated by two experienced observers using dedicated post-processing tools. Ejection fraction (EF) and cardiac output (CO) were calculated and mutually compared using Bland-Altman plots. MRI underestimated the ejection EF by 16.1% with a Bland-Altman interval (B-A) of [-4.35 (-2.48) -0.60]. Sixty-four-slice MDCT overestimated the EF by 2.6% with a relatively wide B-A interval of [-3.40 (0.40) 4.20]. DSCT deviated the least from the known phantom volumes, underestimating the volumes by 0.8% with a B-A interval of [-1.17 (-0.13) 0.91]. CO analysis showed similar results. Furthermore, a good correlation was found between DSCT and MRI for EF and CO results. MRI systematically underestimates functional cardiac parameters, ejection fraction and cardiac output of a moving heart phantom. Sixty-four-slice MDCT underestimates or overestimates these functional parameters depending on the heart rate because of limited spatial resolution. DSCT deviates the least from these functional parameters compared to MRI, EBT and 64-slice MDCT.

Reduced regional myocardial perfusion reserve is associated with impaired contractile performance in idiopathic dilated cardiomyopathy.

Background. In idiopathic dilated cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. Subclinical myocardial ischaemia may contribute to progressive deterioration of left ventricular function. The relation between regional myocardial perfusion reserve (MPR) and contractile performance was investigated.Methods. Patients with newly diagnosed IDC underwent positron emission tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dypiridamole stress), and (18)F-fluorodeoxyglucose viability tracer and a dobutamine stress MRI. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17-segment model.Results. Twenty-two patients were included (age 49+/-11 years; 15 males, LVEF 33+/-10%). With MRI, a total of 305 segments could be analysed. Wall motion abnormalities at rest were present in 127 (35.5%) segments and in 103 (29.9%) during dobutamine stress. Twenty-one segments deteriorated during stress and 43 improved. MPR was significantly higher in those segments that improved, compared with those that did not change or were impaired during stress (1.87+/-0.04 vs. 1.56+/- 0.07 p<0.01.)Conclusion. Signs of regional ischaemia were clearly present in IDC patients. Ischaemic regions displayed impaired contractility during stress. This suggests that impaired oxygen supply contributes to cardiac dysfunction in IDC. (Neth Heart J 2009;17:470-4.).

Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results.

During the last decennium, the role of bone marrow mononuclear cells (BMMC) has been underscored in the healing process after acute myocardial infarction (AMI). Although these cells improve left ventricular recovery after AMI in experimental studies, results from large-scale randomised trials investigating BMMC therapy in patients with AMI have shown contradictory results. To address this issue the HEBE study was designed, a multicentre, randomised trial, evaluating the effects of intracoronary infusion of BMMCs and the effects of intracoronary infusion of peripheral blood mononuclear cells after primary percutaneous coronary intervention. The primary endpoint of the HEBE trial is the change in regional myocardial function in dysfunctional segments at four months relative to baseline, based on segmental analysis as measured by magnetic resonance imaging. The results from the HEBE trial will provide detailed information about the effects of intracoronary BMMC therapy on post-infarct left ventricular recovery. In addition, further analysis of the data and material obtained may provide important mechanistic insights into the contribution of BMMCs to natural recovery from AMI as well as the response to cell therapy. This may significantly contribute to the development of improved cell-based therapies, aiming at optimising post-infarct recovery and preventing heart failure. (Neth Heart J 2008;16:436-9.).

Quantification of global left ventricular function: comparison of multidetector computed tomography and magnetic resonance imaging. a meta-analysis and review of the current literature.

Cardiac morbidity and mortality are closely related to cardiac volumes and global left ventricular (LV) function, expressed as left ventricular ejection fraction. Accurate assessment of these parameters is required for the prediction of prognosis in individual patients as well as in entire cohorts. The current standard of reference for left ventricular function is analysis by short-axis magnetic resonance imaging. In recent years, major extensive technological improvements have been achieved in computed tomography. The most marked development has been the introduction of the multidetector CT (MDCT), which has significantly improved temporal and spatial resolutions. In order to assess the current status of MDCT for analysis of LV function, the current available literature on this subject was reviewed. The data presented in this review indicate that the global left ventricular functional parameters measured by contemporary multi-detector row systems combined with adequate reconstruction algorithms and post-processing tools show a narrow diagnostic window and are interchangeable with those obtained by MRI.

[Delirium attributed to the use of metoprolol]. / Delirant beeld, toegeschreven aan het gebruik van metoprolol.

A 53-year-old man with a known history of alcohol abuse was admitted to hospital after a minor collapse. He had a laceration to the forehead and three rib fractures. Laboratory blood-analysis showed raised non-cholestatic liver-enzyme levels suggesting alcohol-abuse. On history taking the patient was shown to have been suffering from personality changes and multiple hallucinogenic episodes for the previous two years. He had been seen and evaluated by a neurologist to that effect. The patient's family had accepted the situation and thought of it as dementia, probably caused by alcohol abuse. He had been treated for atrial flutter and was taking acenocoumerol, atorvastatin, quinapril and metoprolol 50 mg twice daily as medication. During admission the patient appeared to be suffering from a delirium with complex visual and auditory hallucinations, for which he was given haloperidol. Revision of medication use led to the stopping of metoprolol, which had been started two years earlier. Within 24 hours the delirium had disappeared completely. There was spontaneous fall in the liver enzymes. At his last follow-up, the patient had had no psychiatric symptoms for 6 months. The relationship between stopping metoprolol and the disappearance of the psychosis appeared to be a causal one and this is supported by the limited literature available on this subject.

Myocardial viability assessment: poor correlation between electromechanical cardiac mapping and positron emission tomography in severe coronary artery disease.

BACKGROUND: An intracardial electromechanical mapping system has recently been introduced which offers the ability to perform on-line myocardial viability assessment in the catheterisation laboratory. Only a small number of studies have been performed to validate this potentially very useful technique. AIM: We sought to assess the correlation between viability assessment performed with both positron emission tomography (PET) and electromechanical cardiac mapping (EMM) in patients suffering from severe coronary artery disease, since PET is considered the golden standard in myocardial viability assessment. METHODS: Patients undergoing both EMM and PET analysis were systematically scanned for viability assessment. EMM analysis was performed for both linear local shortening and unipolar voltage. PET analysis consisted of dipyridamole stress and fluoro-deoxy-d-glucose (FDG) measurements. All data were converted to nine-segment bull's-eye maps to allow comparison. One single operator analysed all the data, blinded for clinical status. RESULTS: 34 patients suffering from severe coronary artery disease underwent both PET and EMM analysis. In total 253 EMM segments had more than four contact points and could be used for analysis. Unipolar voltage showed a trend towards lower values in infarcted segments; however, linear local shortening did not show any correlation. CONCLUSION: In this study viability assessment by EMM did not correspond with PET analysis. Although the advantage of having some form of online myocardial assessment is evident, operators should bare in mind that the quantitative EMM measurements are not an absolute substitute for nuclear imaging.