Comparative evaluation of long-term clinical efficacy with catheter-based percutaneous intramyocardial autologous bone marrow cell implantation versus laser myocardial revascularization in patients with severe coronary artery disease.

BACKGROUND: Catheter-based percutaneous laser myocardial revascularization (PMR) and intramyocardial direct bone marrow (BM) cell implantation have been investigated to treat patients with severe coronary artery disease (CAD). In both therapeutic approaches, direct local myocardial injury might be a common mechanism to induce therapeutic angiogenesis. METHODS: We studied the long-term clinical outcome in 16 patients with severe CAD who received either catheter-based PMR (n = 8) or intramyocardial autologous BM cell implantation (n = 8) as guided by electromechanical mapping. RESULTS: There were no significant differences in the baseline characteristics and the number of injection versus the number of laser pulse delivered between the 2 groups (P > .05). As compared with baseline, the New York Heart Association functional class and the number of anginal episodes were significantly reduced at 3- and 6-month follow-up in both BM and PMR groups (P < .05). However, the improvement in the New York Heart Association class and the reduction in anginal episodes at 18 months were only persisted in the BM group (P < .05) but not in the PMR group (P > .05). Furthermore, there were significant improvements in exercise time at 6- and 18-month follow-up, and the extent of stress-induced perfusion single-photon emission computed tomography defects at 6-month follow-up in BM group, as compared with baseline (all P < .05), but not in the PMR group (all P > .05). As compared with baseline, there were no significant changes in the total quality of life scores during follow-up in both groups (all P > .05). CONCLUSIONS: The results of this study demonstrated that the catheter-based intramyocardial autologous BM cell implantation might be more effective than PMR in improving symptoms and exercise capacity in patients with severe CAD. The beneficial effect of direct intramyocardial injection was over and beyond those noted in patients treated with PMR, suggesting a potential direct therapeutic effect of BM cells, rather than local myocardial injury alone on chronic ischemic myocardium.

Safety of catheter-based intramyocardial autologous bone marrow cells implantation for therapeutic angiogenesis.

The long-term safety and efficacy of autologous bone marrow cell implantation into the myocardium remains undefined. We studied the long-term clinical outcome of 12 patients with severe coronary artery disease who underwent electromechanical mapping-guided catheter-based autologous bone marrow cell implantation. Magnetic resonance imaging at 3 and 6 months showed no evidence of intramyocardial tumor formation, myocardial damage, or worsening of left ventricular ejection fraction. No sustained arrhythmia was detected on 24-hour Holter monitoring. After 44 +/- 10 months of follow-up, 1 patient had died of stroke at 8 months and another patient had died of myocardial infarction at 20 months. Computed tomography at 36 months or postmortem examination showed no tumor formation or intramyocardial calcification at the treated sites, and no sustained ventricular arrhythmia or sudden death was observed. Autologous bone marrow cell implantation into the ischemic human myocardium was not associated with long-term major adverse events regarding tumor, scar, or calcification formation, and the arrhythmogenic risk was low.

Effect of endomyocardial laser channels on regional innervation shown with (125)I-MIBG and autoradiography.

UNLABELLED: The aim of this study was to map regional innervation against regional flow early after laser channel placement using autoradiography in a porcine model. METHODS: Four juvenile male swine underwent left ventricular mapping using a catheter-based mapping system and laser treatment with 20-30 channels to the mid and distal anterior wall of the left ventricle. Three days later animals were injected with 37 MBq (125)I-metaiodobenzylguanidine (MIBG) followed in 3 h with 1,110 MBq (99m)Tc-sestamibi; 1 h later the animals were killed. Hearts were removed, perfusion fixed, and sliced into 1-cm slices. The slices best showing laser holes were selected, and circumferential sections were taken for autoradiography and hematoxylin-eosin staining. Phosphor screens were exposed for (99m)Tc and (125)I, and images were processed. The MIBG image was subtracted from the methoxyisobutylisonitrile (MIBI) image and vice versa, and color tables were applied to the difference images and overlaid on the perfusion images. Quantitative analysis of the light image data was also performed. RESULTS: Thirty-three sections from the last 3 experiments were analyzed. Acoustic damage from 30 laser channels was identified from the hematoxylin-eosin sections. Reduced MIBG relative to regional flow was seen in surrounding tissue corresponding to only 1 channel. There was no statistically significant difference in light units expressed as (MIBG - MIBI)/maximal MIBG value between laser channels and unmarked myocardial map regions. The regions identified from the color table on the map as low MIBG relative to MIBI were significantly lower than remaining laser channels and remaining myocardium. Mean light units for the regions with high MIBG relative to MIBI were significantly higher than the remaining laser channels and remaining myocardium. CONCLUSION: Using a high-resolution technique correlated with microscopic pathology in an animal model, there is negligible regional denervation 3 d after placement of endomyocardial laser channels.

The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent.

OBJECTIVES: This study sought to compare the efficacy and safety results after coronary implantation of a combined sirolimus-eluting CD34 antibody coated Combo stent (OrbusNeich Medical, Ft. Lauderdale, Florida) with the paclitaxel-eluting Taxus Liberté stent (PES) (Boston Scientific, Natick, Massachusetts). This report summarizes the first-in-man randomized, controlled multicenter REMEDEE trial (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) angiographic, intravascular ultrasound, and clinical results up to 12 months. BACKGROUND: Drug-eluting stents have limited restenosis and reintervention but are complicated by especially late and very late stent thrombosis and accelerated neoatherosclerosis. Alternative or adjunct technologies should address these limitations. METHODS: One hundred eighty-three patients with de novo native coronary artery stenoses were randomized 2:1 to Combo stent or PES implantation. The primary endpoint is the angiographic in-stent late lumen loss at 9 months, which was tested for noninferiority between the 2 stent groups. Secondary endpoints include the occurrence of major adverse cardiac events. RESULTS: The Combo stent was found to be noninferior to the PES in 9-month angiographic in-stent late lumen loss with 0.39 ± 0.45 mm versus 0.44 ± 0.56 mm (pnoninferiority = 0.0012). At 12 months, the occurrence of major adverse cardiac events was 8.9% in the Combo group and 10.2% in the PES group (p = 0.80) with no difference in mortality, occurrence of myocardial infarction, or target lesion revascularization. No stent thrombosis was reported in either group. CONCLUSIONS: In the REMEDEE trial the Combo stent has shown to be effective by meeting the primary noninferiority angiographic endpoint and safe, with an overall low rate of clinical events in both stent groups, including no stent thrombosis up to 12 months.

Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial).

AIMS: Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). METHODS AND RESULTS: We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. CONCLUSION: Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.

Validation of R wave voltage endomyocardial mapping to assess myocardial fibrosis: comparison with thallium and dobutamine echocardiography in a swine model.

The first aim of this study was to validate R wave voltage values measured with a catheter-based three-dimensional mapping system (NOGA, Biosense) against myocardial fibrosis in a swine model of ameroid placement. The second aim was to correlate the UPV maps with thallium uptake and low-dose dobutamine echocardiography. The electromechanical catheter mapping system can be used to guide endomyocardial laser therapy and direct gene delivery to the myocardium. The accuracy of R wave voltage in identifying myocardial fibrosis and its comparison with other imaging technologies against histopathology has not been fully investigated in an animal model. Ameroid constrictors were placed on 24 vessels in 14 swine. Wall motion abnormalities by echocardiography were detected in distribution of the constrictors at 22 +/- 10 days. Animals underwent rest and delayed thallium imaging, low-dose dobutamine echocardiography, and R wave voltage mapping. Animals were sacrificed, hearts were removed, 4-micron slices were stained, and fibrosis was quantified. Five control animals were studied to obtain segment normalization. There was significant agreement between each imaging modality and fibrosis by chi-square analysis. The correlation for segment normalized thallium uptake and segment normalized UPV score versus fibrosis were both significant (P < 0.001) with an r2 value of 0.362 vs. thallium, and r2 = 0.445 vs. UPV. The correlation was improved using log of UPV vs. fibrosis (r = 0.532). These results help validate R wave voltage mapping as an imaging technique to identify myocardial fibrosis.