Transmyocardial Revascularization Channels Research Articles

Synergistic Effect of Transmyocardial Revascularization and Platelet-Rich Plasma on Improving Cardiac Function After Coronary Artery Bypass Grafting.

Background Coronary artery disease (CAD) is a global health burden, contributing to mortality and morbidity. A proportion of patients with CAD suffer from diffuse CAD, where conventional revascularization techniques such as percutaneous coronary intervention and coronary artery bypass grafting (CABG) may be insufficient to adequately restore myocardial perfusion. Transmyocardial revascularization (TMR) uses a laser to create microscopic channels in the myocardium, inducing inflammation, angiogenesis, and neovascularization to improve perfusion to ischemic regions. Platelet-rich plasma (PRP) is an autologous concentrate of platelets that contains a myriad of growth factors and bioactive proteins, which have been shown to promote tissue regeneration and wound healing. The combination of TMR and PRP therapies has been proposed to synergistically enhance myocardial revascularization and functional recovery in patients with advanced CAD undergoing surgical revascularization. Methods This study evaluated the efficacy of combining TMR and PRP with CABG in improving cardiac function in diffuse CAD patients. Fifty-two patients were randomized to CABG alone (n = 16), CABG+TMR (n = 17), CABG+PRP (n = 10), and CABG+TMR+PRP (n = 9). TMR was performed using a holmium:YAG laser to create 10 channels in the inferolateral left ventricular wall. PRP was prepared from autologous whole blood and injected into the myocardium adjacent to the TMR channels. Cardiac function was assessed using speckle-tracking echocardiography preoperatively, postoperatively, and at one-year follow-up. Adverse events, including post-operative atrial fibrillation, acute kidney injury, and readmissions, were also recorded. Statistical analyses were performed to compare outcomes between the treatment groups. Results The CABG+TMR+PRP group showed significantly improved global longitudinal strain (GLS) at one year compared to CABG alone (mean GLS -15.96 vs -12.09, p = 0.02). Post-operative left ventricular ejection fraction trended higher in the TMR+PRP group (57.78%) vs other groups, but not significantly. Post-operative atrial fibrillation was higher in the TMR+PRP group (67% vs 25%, p = 0.04), potentially reflecting increased inflammation. No significant differences were observed in other adverse events. Conclusions The results of this study suggest a synergistic benefit of combining TMR and PRP therapies as an adjunct to CABG in patients with diffuse CAD. The significant improvement in GLS at one year in the TMR+PRP group compared to CABG alone indicates enhanced myocardial remodeling and functional recovery, which may translate to improved long-term outcomes. The higher incidence of postoperative atrial fibrillation in the TMR+PRP group warrants further investigation but may reflect the heightened inflammatory response necessary for angiogenesis and tissue regeneration. Prospective, randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings and optimize treatment protocols. Nonetheless, concomitant TMR+PRP therapy represents a promising approach to augmenting myocardial revascularization and recovery in patients with advanced CAD undergoing surgical revascularization.

Robotically assisted, completely endoscopic transmyocardial revascularization is feasible.

The purpose of this study was to assess the feasibility of an endoscopic, optical-fiber-based, laser delivery system (LDS) developed to perform sole-therapy transmyocardial revascularization (TMR) in a totally endoscopic, robotically assisted operation. Forty-two patients were enrolled in a multicenter, prospective, single-arm clinical trial conducted at four US centers between 2005 and 2007. Transmyocardial revascularization was performed completely endoscopically with robotic assistance, introducing the Holmium:Yttrium aluminum garnet (YAG) LDS via a 5-mm port. Completion of the operation endoscopically defined procedural success. Clinical data were recorded before, during, and at least 30 days after the procedure. All patients had Canadian Cardiovascular Score angina class IV at baseline. The mean ejection fraction was 49% (range [R], 28-71), the mean age was 59.1 years (R, 36-80), 71% (30/42) were men, 86% (36/42) underwent previous coronary artery bypass grafting surgery, and 76% (32/42) underwent prior coronary stenting. Procedural success was accomplished in 93% (39/42). For the procedural successes, the mean number of TMR channels was 32 (R, 16-50), the median operative time was 88 minutes (R, 48-250 minutes), and the median length of stay postoperatively was 2.5 days (R, 1-10). There was no operative or 30-day mortality, and no patient received any transfusion. At 30 days, freedom from major adverse cardiac events was 95% (two patients had transient congestive heart failure). At the median 6-month follow-up (single-center data, n = 12), the mean (SD) Canadian Cardiovascular Score angina score was 1.3 (0.05) (P < 0.001 vs baseline). Robotically assisted TMR can be performed using an endoscopic, optical-fiber-based LDS, with high procedural success, avoidance of early adverse clinical events, and potential for successful angina relief.

Transmyocardial Revascularization Induces Mesenchymal Stem Cell Engraftment in Infarcted Hearts

Transmyocardial revascularization (TMR) prior to mesenchymal stem cell (MSC) transplantation augments repair of infarcted hearts. We evaluated the effects of TMR on homing and engraftment of circulating MSCs and mediators of this effect. Three weeks after left anterior descending coronary artery ligation in female rats, 10-channel needle TMR was performed in the infarct, followed by daily intravenous injections of 1 million male MSCs for 5 days. Control rats had MSC infusions without TMR (n=16/group). Donor MSC survival was evaluated at 3 days and at 1 week by quantitative polymerase chain reaction, as well as expression of stem cell factor (SCF), stromal derived factor-1 (SDF-1), c-kit, and chemokine receptor type 4 (CXCR4). The MSCs engrafted into the infarct, clustering around TMR channels. The MSC engraftment was greater in TMR hearts at 3 days and at 1 week. Both SCF (p=0.03) and c-kit (p=0.01) were upregulated by TMR at 3 days, but their levels fell at 1 week (p=0.3, p=0.5, respectively). The SDF-1 levels were higher in TMR hearts at both 3 days (p=0.04) and at 1 week (p=0.04). The CXCR4 was upregulated early by TMR (p=0.0002) but levels dropped dramatically at 1 week (p=0.045). Transmyocardial revascularization induces transmigration and engraftment of circulating MSCs. Post TMR, the transcription of SCF and c-kit is rapid and corresponds temporally to MSC engraftment, while SDF-1 levels rise slowly. The CXCR4 is also transiently upregulated. The TMR-augmented repair of infarcted hearts by stem cell transplantation may be mediated by a novel mechanism: transmigration and engraftment of circulating progenitor cells.

Intramyocardial Injection of Autologous Platelet-Rich Plasma Combined with Transmyocardial Revascularization

Transmyocardial revascularization (TMR) can improve refractory angina but does not consistently demonstrate an effect on myocardial function. Recent studies suggest a synergistic effect between TMR and exogenously supplied growth factors. We evaluated the clinical role of intramyocardial injection of autologous platelet-rich plasma (PRP) in conjunction with TMR. Twenty-five nonrevascularizable patients with class III/IV angina underwent minimally invasive sole therapy TMR during a 5-year period at a single institution. Group 1 (14 patients) underwent TMR alone while group 2 (11 patients) underwent TMR plus injection of PRP (Magellan plasma separator) between TMR channels. Blinded angina assessment and ejection fraction (EF) were measured preoperatively and at 6 months postoperatively. Baseline EF (57 +/- 10% vs. 50 +/- 7%), angina class (3.7 +/- 0.5 vs. 3.7 +/- 0.5), and the number of channels (48 +/- 5 vs. 48 +/- 4) were statistically similar in both groups. At 6 months, two class angina relief was similar in both groups (92% vs. 100%, p = 0.4); however, the TMR + PRP group had a lower average angina score (1.3 vs. 0.4, p = 0.07) and more were angina free (23% vs. 78%, p = 0.04) than the TMR-alone group. EF improved in the TMR + PRP group (-2.0% vs. +9.0%, p = 0.07) compared to the TMR-alone group. Two 30-day morbidities occurred in the TMR-alone group (atrial fibrillation and left pleural effusion) and one mortality occurred in the TMR + PRP group. Intramyocardial injection of autologous PRP combined with TMR may be more efficacious at relieving angina and improving myocardial function than TMR alone.

Combined transmyocardial revascularization and cell-based angiogenic gene therapy increases transplanted cell survival

We hypothesized that pretreatment of an infarcted heart by mechanical transmyocardial revascularization (TMR) before transplantation of bone marrow cells (BMCs) or BMC-expressing angiogenic growth factors would increase transplanted BMC survival and enhance myocardial repair. Female Lewis rats underwent coronary ligation 3 wk before creation of 10 needle TMR channels (3 groups) or no TMR (3 groups), followed by transplantation of 3 x 10(6) male donor BMCs, BMC transfected with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1) (BMC + VBI), or medium alone. At 1, 3, and 7 days, we evaluated transplanted cell survival, vascular densities, and left ventricular (LV) function (N = 4 per group x 6 groups x 3 time points). At 3 days, vascular densities in the scar were increased by TMR + BMC + VBI and by BMC + VBI (P < 0.05), and at 7 days, vascular densities were greatest in rats receiving TMR + BMC + VBI (P < 0.05). Transplanted cell survival at 3 and 7 days was increased by TMR and by BMC + VBI. Combined therapy with TMR + BMC + VBI resulted in the greatest cell survival at 3 days (P < 0.05) versus BMC. After 7 days, LV ejection fraction (LVEF) was lowest in rats receiving neither BMC nor TMR and greatest in rats receiving TMR + BMC + VBI (P = 0.004). We concluded that mechanical pretreatment of infarcted myocardium by TMR enhances the effect of subsequent cell-based gene therapy on transplanted cell survival, angiogenesis, and LV function. Scar pretreatment with TMR combined with cell-based multigene therapy may maximize myocardial repair.

Functional comparison of transmyocardial revascularization by mechanical and laser means

Background. As a result of the clinical benefit observed in angina patients treated by transmyocardial revascularization (TMR) with a laser, interest in mechanical TMR has been renewed. Although the injury induced by mechanical TMR is similar to laser TMR, the resultant impact on myocardial contractility is unknown. The purpose of this study was to determine whether mechanical TMR improves ventricular function as compared with laser TMR in chronically ischemic myocardium. Methods. After establishing an area of chronic myocardial ischemia, 25 domestic pigs were randomized to treatment by: excimer laser (group I), a hot needle (50°C) (group II), a normothermic needle (group III), an ultrasonic needle (40 KHz) (group IV), or no treatment (group V). All devices create a transmural channel of the same diameter; 22 ± 1 transmural channels were created in each animal. Regional myocardial contractility was assessed by measuring ventricular wall thickening at rest and with dobutamine stress echocardiography. Six weeks after revascularization, the animals were restudied at rest and with stress. Postsacrifice and histologic analysis of angiogenesis and TMR effects was then assessed. Results. Laser TMR provided significant recovery of ischemic myocardial function. This improvement in contractility after laser TMR was a 75% increase over the baseline function of the ischemic zone ( p < 0.01). Mechanical TMR provided no significant improvement in function posttreatment. In fact, TMR achieved with an ultrasonic needle demonstrated a 40% worsening of the contractility versus the pretreatment baseline ( p < 0.05). Histologic analysis demonstrated a significant increase in new blood vessels in the ischemic zone after laser TMR, which was not demonstrated for any of the other groups ( p < 0.05). Additionally, evaluation of the mechanical TMR channels demonstrated significant scarring, which correlated with the functional results. Conclusions. Using devices to create an injury analogous to the laser, mechanical TMR failed to improve the function of chronically ischemic myocardium. Only laser TMR significantly improved myocardial function.

Excimer laser (308 nm) based transmyocardial laser revascularization: Effects of the lasing parameters on myocardial histology

The effect of the excimer laser (308 nm) parameters on transmyocardial revascularization (TMR) channels is not well defined. This study investigates the influence of the pulse repetition rate, the size of the delivery catheter and its advancement speed on the morphology of TMR channels in vivo. Myocardial ablation was performed in a porcine model (N = 27) using multifiber catheters of 1.0 and 1.4 mm in diameter. The catheters were advanced into the myocardium at different speeds (1.27 and 2.54 mm/sec) while ablating at various repetition rates (10-80 Hz). The radiant exposure was kept at 35 mJ/mm(2) throughout the experiments. The channel histology was quantified by digital microscopy. The channel cross-sectional area and the extent of the thermal damage decrease as the catheter advancement speed exceeds the ablation speed and vice versa. Within the parameters tested, advancement speed of about 1.3 mm/sec and pulse repetition rates of 40 Hz produce channels of size comparable to the catheter's diameter with moderate thermomechanical damage. The repetition rate, catheter size, and catheter advancement speed are closely intertwined and crucial to the histological outcome of excimer laser based TMR.

Transmyocardial revascularization aggravates myocardial ischemia around the channels in the immediate phase.

We examined whether transmyocardial revascularization (TMR) relieves myocardial ischemia by increasing regional perfusion via the transmural channels in acute canine experiments. Regional blood flow during transient coronary ligation (2 min) was compared before and 30 min after TMR, and at the third transient ischemia the mid-left ventricle (LV) was cut and immediately frozen along the short axis for the analysis of NADH fluorescence in the regions around the TMR channels. In low-resolution analysis (2-4 g tissue or 2-3 cm(2) area), regional perfusion was not significantly altered after TMR, and NADH fluorescence was observed throughout the ischemic region without significant spatial variation. High-resolution analysis (2.8 mg, 1 mm x 1 mm) revealed that the flow after TMR was lower, and NADH fluorescence was higher in the regions close to the channels (1-2 mm) than in the regions 3-4 mm away from them. Creating TMR channels did not improve the regional perfusion and rather aggravated the local ischemia in the vicinity of the channels in the immediate phase.

Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures

Background. Transmyocardial laser revascularization (TMLR), which has been shown to reduce angina in clinical trials, was originally based on the belief that laser channels are unique and can remain patent. An increasing body of evidence indicates otherwise, and transmyocardial revascularization (TMR) angiogenesis is currently thought to be induced by nonspecific inflammatory response to tissue injuries. We tested the hypothesis that mechanical transmyocardial revascularization (TMMR) may induce angiogenic responses similar to that seen with lasers. Methods. Ameroid constrictors were implanted around proximal circumflex arteries of porcine hearts. Six weeks later, they were randomly assigned (n = 5 each) to receive 10 transmural channels in the ischemic zone by a carbon dioxide laser (group I) or by a needle (group II). A third group (group III) had 30 needle channels in the same area, while a control group (group IV) received no TMR. The hearts were harvested 1 week later, and, using immunohistochemistry, vascular endothelial growth factor (VEGF) expression was studied and quantified by computerized morphometric analysis. Densities of vascular structures positively stained for VEGF per high-power field (HPF) were also compared. Results. Virtually no TMR channels remained patent histologically. Group III had a significant higher level of total VEGF expression (14.18 ± 0.78 mm 2) compared with group I (7.07 ± 2.06 mm 2, p < 0.001) and group II (4.74 ± 3.35 mm 2, p < 0.001). Vascular density was significantly elevated in all treatment groups compared with the control (group I, 7.7 ± 0.8/HPF vs group II, 4.5 ± 2.3/HPF vs group III, 8.1 ± 0.6/HPF vs group IV, 1.1 ± 0.5/HPF). Conclusions. In view of the significant cost implications, our findings that needle punctures may also induce angiogenic response comparable with that with laser suggest that it is justifiable and desirable to include a TMMR arm for comparison with TMLR in future clinical trials.