Tirza Springeling

First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction.

To the Editor: nnIn preclinical animal models of acute myocardial infarction (AMI), administration of freshly isolated adipose tissue–derived regenerative cells (ADRCs) immediately after the AMI improved left ventricular (LV) function and myocardial perfusion ([1,2][1]). The predominant working

A Prospective Open Study of the Efficacy of High-Dose Recombinant Hepatitis B Rechallenge Vaccination in HIV-Infected Patients

Double-dose hepatitis B virus revaccination of human immunodeficiency virus (HIV)-infected patients proved to be effective in 50.7% of 144 patients who had previously failed to respond to standard doses. In the multivariate analysis, female patients were found to have a significantly better response (P= .03). The effect of age on the response depended on the viral load at the time of revaccination. For patients with a detectable HIV RNA load, the effect of age was stronger (odds ratio [OR], 0.34 per 10 years older [95% confidence interval {CI}, 0.16-0.72]; P= .005) than for patients with an undetectable HIV RNA load (OR, 0.74 per 10 years older [95% CI, 0.50-1.09]; P= .12).

Complete Percutaneous Revascularization for Multivessel Disease in Patients With Impaired Left Ventricular Function: Pre- and Post-Procedural Evaluation by Cardiac Magnetic Resonance Imaging

OBJECTIVESnThe aim of this study was to investigate the effect of complete, incomplete, and unsuccessful revascularization by percutaneous coronary intervention (PCI) on left ventricular ejection fraction (EF) in patients with multivessel disease and impaired left ventricular function and assess the diagnostic accuracy of cardiac magnetic resonance imaging (MRI) for improvement in EF.nnnBACKGROUNDnThe effect of PCI for multivessel coronary artery disease on long-term myocardial function and the predictive value of cardiac MRI on global function are incompletely investigated.nnnMETHODSnCardiac MRI was performed in patients with multivessel disease before and 6 months after complete revascularization (n = 34) or incomplete revascularization (n = 22) or in patients without successful revascularization (n = 15). For the prediction of recovery of EF, wall thickening was quantified on cine images at rest and during 5- and 10-microg/kg/min dobutamine. The transmural extent of infarction was quantified on delayed enhancement cardiac MRI.nnnRESULTSnThe EF improved significantly after complete revascularization (46 +/- 12% to 51 +/- 13%; p < 0.0001) but did not change after incomplete (49 +/- 11% to 49 +/- 10%; p = 0.88) or unsuccessful revascularization (49 +/- 13% to 47 +/- 13%; p = 0.11). Sensitivity, specificity, positive and negative predictive value for the prediction of improvement in EF of >4% after PCI were 100%, 75%, 74%, and 100%, respectively, for dobutamine-cardiac MRI and 70%, 77%, 70%, and 77%, respectively, for delayed enhancement-cardiac MRI.nnnCONCLUSIONSnComplete revascularization for multivessel coronary artery disease improves EF, whereas EF did not change in patients after incomplete or unsuccessful revascularization. Improvement in EF can be predicted by performing cardiac MRI before PCI.

Reversible jump MCMC methods for fully automatic motion analysis in tagged MRI

Tagged magnetic resonance imaging (tMRI) is a well-known noninvasive method for studying regional heart dynamics. It offers great potential for quantitative analysis of a variety of kine(ma)tic parameters, but its clinical use has so far been limited, in part due to the lack of robustness and accuracy of existing tag tracking algorithms in dealing with low (and intrinsically time-varying) image quality. In this paper, we evaluate the performance of four frequently used concepts found in the literature (optical flow, harmonic phase (HARP) magnetic resonance imaging, active contour fitting, and non-rigid image registration) for cardiac motion analysis in 2D tMRI image sequences, using both synthetic image data (with ground truth) and real data from preclinical (small animal) and clinical (human) studies. In addition we propose a new probabilistic method for tag tracking that serves as a complementary step to existing methods. The new method is based on a Bayesian estimation framework, implemented by means of reversible jump Markov chain Monte Carlo (MCMC) methods, and combines information about the heart dynamics, the imaging process, and tag appearance. The experimental results demonstrate that the new method improves the performance of even the best of the four previous methods. Yielding higher consistency, accuracy, and intrinsic tag reliability assessment, the proposed method allows for improved analysis of cardiac motion.

Myocardial ‘No-Reflow’ Prevention

Despite achievement of optimal epicardial coronary flow in the majority of patients treated for ST-segment elevation myocardial infarction (STEMI) by primary percutaneous coronary intervention (PPCI), myocardial no-reflow is a common phenomenon occurring in 5 to 50% of patients. The no-reflow phenomenon is a predictor of infarct size and an independent predictor of mortality both in the short and long term. Prevention of no-reflow is therefore a crucial step in improving prognosis of patients with STEMI. Several strategies including pharmacological and mechanical ones have been developed to improve microvascular perfusion in the setting of a myocardial infarction. Prevention starts by conservation of the microvascular reserve especially in patients at high risk of acute coronary syndromes such as diabetes patients. Optimal glycaemic control and the use of statins have been shown to reduce no-reflow in this context. Reducing ischaemic time by shortening door to balloon times, administration of intracoronary GP IIb/IIIa antagonists during PPCI and the use of manual aspiration thrombectomy have been shown to result in better myocardial perfusion and improved clinical outcome in major trials. In this review we discuss some of these major trials and studies of other therapeutic options that aim to prevent the no-reflow phenomenon.

Evolution of reperfusion post-infarction ventricular remodeling: New MRI insights

BACKGROUNDnOur current understanding is that left ventricular (LV) remodeling after acute myocardial infarction (AMI) is caused by expansion of the infarcted myocardium with thinning of the wall and eccentric hypertrophy of the remote myocardium. To study the geometric changes in the remodeling process after reperfused AMI we used cardiac magnetic resonance imaging (CMR).nnnMETHODSnNine juvenile swine underwent a 120-min occlusion of the left circumflex coronary artery followed by reperfusion. CMR was performed at 3 and 36 days post-infarction. Global and regional LV remodeling was assessed including geometric changes of infarcted and remote myocardium; infarct longitudinal length (mm), mean circumferential length (mm), total infarct surface (mm(2)), end-diastolic wall thickness (EDWT) (mm) and transmural extent of infarction (TEI).nnnRESULTSnFrom 3 days to 36 days post-infarction end-diastolic volume increased by 43% (p<0.01). Infarct mass decreased by 36% (p<0.01), mainly by reduction of EDWT with 26%, while mean infarct circumferential length and longitudinal infarct length did not change. Remote myocardial mass increased by 23%, which was the result of an increase in its circumferential length from 95 ± 10 mm to 113 ± 11 mm (p<0.01), with no change in its EDWT. In contrast, EDWT in the infarct, peri-infarct and border zone decreased.nnnCONCLUSIONSnContrary to the widely held view the present, using CMR measurements, shows that post-infarction remodeling was not associated with expansion of the infarcted myocardium. These findings suggest that eccentric hypertrophy of the remote myocardium, but not expansion of the infarct region, is responsible for left ventricular dilatation after AMI.

VEGF165A microsphere therapy for myocardial infarction suppresses acute cytokine release and increases microvascular density but does not improve cardiac function

Angiogenesis induced by growth factor-releasing microspheres can be an off-the-shelf and immediate alternative to stem cell therapy for acute myocardial infarction (AMI), independent of stem cell yield and comorbidity-induced dysfunction. Reliable and prolonged local delivery of intact proteins such as VEGF is, however, notoriously difficult. Our objective was to create a platform for local angiogenesis in human-sized hearts, using polyethylene-glycol/polybutylene-terephthalate (PEG-PBT) microsphere-based VEGF165A delivery. PEG-PBT microspheres were biocompatible, distribution was size dependent, and a regimen of 10 × 10(6) 15-μm microspheres at 0.5 × 10(6)/min did not induce cardiac necrosis. Efficacy, studied in a porcine model of AMI with reperfusion rather than chronic ischemia used for most reported VEGF studies, shows that microspheres were retained for at least 35 days. Acute VEGF165A release attenuated early cytokine release upon reperfusion and produced a dose-dependent increase in microvascular density at 5 wk following AMI. However, it did not improve major variables for global cardiac function, left ventricular dimensions, infarct size, or scar composition (collagen and myocyte content). Taken together, controlled VEGF165A delivery is safe, attenuates early cytokine release, and leads to a dose-dependent increase in microvascular density in the infarct zone but does not translate into changes in global or regional cardiac function and scar composition.

Intermittent pacing therapy favorably modulates infarct remodeling

Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2xa0h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2xa0±xa04.4% reduction in infarct thickness (Pxa0≤xa00.05), whereas in IPT pigs it was mainly due to a 35.7xa0±xa04.5% decrease in the number of infarct segments (Pxa0≤xa00.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9xa0±xa02.1%) compared to MI control (5.4xa0±xa01.6%; Pxa0≤xa00.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5xa0weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content.

Comparison between transmural and non-transmural infarction and the area at risk using T2 weighted imaging

T2 weighted cardiac imaging is currently used as a method to quantify the area at risk (AAR). Recently Ubach et al showed that the AAR exceeds the border of the infarct especially in patients with early reperfusion or aborted myocardial infarction.

Changes in ascending aorta dimensions, aortic valve function and systolic ventricular function over time in patients with congenital aortic stenosis

Bicuspid aortic valve (BAV) is one of the most common congenital heart malformations and is a frequent cause of aortic valve stenosis (AoS).