In experimental studies, mesenchymal stem cell (MSC) transplantation in acute myocardial infarction (AMI) models has been associated with enhanced neovascularization and myogenesis. Clinical data however, are scarce. Therefore, the present study evaluates the safety and feasibility of intramyocardial MSC injection in nine patients, shortly after AMI during short-term and 5-year follow-up. Periprocedural safety analysis demonstrated one transient ischemic attack. No other adverse events related to MSC treatment were observed during 5-year follow-up. Clinical events were compared to a nonrandomized control group comprising 45 matched controls. A 5-year event-free survival after MSC-treatment was comparable to controls (89 vs. 91 %, P = 0.87). Echocardiographic imaging for evaluation of left ventricular function demonstrated improvements up to 5 years after MSC treatment. These findings were not significantly different when compared to controls. The present safety and feasibility study suggest that intramyocardial injection of MSC in patients shortly after AMI is feasible and safe up to 5-year follow-up.

PurposeThe aim of the current study was to evaluate the relationship between the site of latest mechanical activation as assessed with gated myocardial perfusion SPECT (GMPS), left ventricular (LV) lead position and response to cardiac resynchronization therapy (CRT).MethodsThe patient population consisted of consecutive patients with advanced heart failure in whom CRT was currently indicated. Before implantation, 2-D echocardiography and GMPS were performed. The echocardiography was performed to assess LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). The site of latest mechanical activation was assessed by phase analysis of GMPS studies and related to LV lead position on fluoroscopy. Echocardiography was repeated after 6 months of CRT. CRT response was defined as a decrease of ≥15% in LVESV.ResultsEnrolled in the study were 90 patients (72% men, 67±10 years) with advanced heart failure. In 52 patients (58%), the LV lead was positioned at the site of latest mechanical activation (concordant), and in 38 patients (42%) the LV lead was positioned outside the site of latest mechanical activation (discordant). CRT response was significantly more often documented in patients with a concordant LV lead position than in patients with a discordant LV lead position (79% vs. 26%, p<0.01). After 6 months, patients with a concordant LV lead position showed significant improvement in LVEF, LVESV and LVEDV (p<0.05), whereas patients with a discordant LV lead position showed no significant improvement in these variables.ConclusionPatients with a concordant LV lead position showed significant improvement in LV volumes and LV systolic function, whereas patients with a discordant LV lead position showed no significant improvements.

PurposeDespite its high prognostic value, widespread clinical implementation of 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is hampered by a lack of validation and standardization. The purpose of this study was to assess the reliability of planar 123I-MIBG myocardial scintigraphy in patients with heart failure (HF).MethodsPlanar myocardial MIBG images of 70 HF patients were analysed by two experienced and one inexperienced observer. The reproducibility of early and delayed heart-to-mediastinum (H/M) ratios, as well as washout rate (WR) calculated by two different methods, was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman analysis. In addition, a subanalysis in patients with a very low H/M ratio (delayed H/M ratio <1.4) was performed. The delayed H/M ratio was also assessed using fixed-size oval and circular cardiac regions of interest (ROI).ResultsIntra- and interobserver analyses and experienced versus inexperienced observer analysis showed excellent agreement for the measured early and delayed H/M ratios and WR on planar 123I-MIBG images (the ICCs for the delayed H/M ratios were 0.98, 0.96 and 0.90, respectively). In addition, the WR without background correction resulted in higher reliability than the WR with background correction (the interobserver Bland-Altman 95 % limits of agreement were −2.50 to 2.16 and −10.10 to 10.14, respectively). Furthermore, the delayed H/M ratio measurements remained reliable in a subgroup of patients with a very low delayed H/M ratio (ICC 0.93 for the inter-observer analysis). Moreover, a fixed-size cardiac ROI could be used for the assessment of delayed H/M ratios, with good reliability of the measurement.ConclusionThe present study showed a high reliability of planar 123I-MIBG myocardial scintigraphy in HF patients, confirming that MIBG myocardial scintigraphy can be implemented easily for clinical risk stratification in HF.

BackgroundAssessment of cardiac innervation using single-photon emission computer tomography (SPECT) is less established than planar imaging, but may be more suitable for quantification. Therefore, a volumetric quantification of I-123 MIBG SPECT acquisitions was performed. Reproducibility, the effects of extra cardiac I-123 MIBG uptake and the relation with conventional planar indices were evaluated.Methods54 patients referred for planar and SPECT I-123 MIBG acquisitions were included. Ellipsoidal or box-shaped volumes of interest were placed on the left ventricle, cardiac lumen, mediastinum, lung and liver. SPECT segmentation was performed twice in all patients. Indices were determined based on the heart-to-mediastinum (HM), myocardial wall-to-mediastinum and myocardial wall-to-lumen regions. HM ratios and washout rates were also determined based on anterior planar images.ResultsCardiac count densities were highly reproducible (CV 1.5-5.4, ICC 0.96-0.99) and inter-rater variability was low (CV 1.8-6.8, ICC 0.94-0.99). Mediastinal uptake was an important explanatory variable of uptake in the entire heart (early R2 = 0.36; delayed R2 =0.43) and myocardial wall (early R2 = 0.28; delayed R2 = 0.37). Lung washout was an explanatory variable of organ washout of the heart (heart R2 = 0.38; myocardial wall R2 = 0.33). In general, SPECT indices showed moderate-to-good correlations with the planar uptake (PCC 0.497-0.851).ConclusionBy applying a volumetric segmentation method we were able to segment the heart in all patients. SPECT I-123 MIBG quantification was found to be highly reproducible and had a moderate to good correlation with the planar indices.

BackgroundHepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (90Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma.Methods/designIn this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness.Trial registrationNCT01381211