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

Abstract

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.

Keywords: coronary artery bypass grafting (cabg); coronary artery disease (cad); platelet-rich plasma (prp); speckle tracking echocardiography (ste); transmyocardial revascularization (tmr).

Figure 1. Transmyocardial revascularization using the handpiece.

Transmyocardial revascularization (TMR) was performed on the heart by lasing channels in the myocardium, with an energy output of 7 W per laser pulse using the Ho:YAG fiber optic hand tool. The gray region seen on the heart represents an infarcted zone following ischemic damage. Depending on the ischemic region and the size of the patient’s heart, a total of 20–40 channels are created using the TMR laser handpiece. Typically, channels are placed on the anterolateral, apical, and inferoapical regions of the heart. The original figure was created by Dr. Zain Khalpey for a previous publication [19].

Figure 2. Demographic details of the four study groups.

(A) Age; (B) male sex. No significant differences were found between study groups. Statistical comparisons were undertaken by comparing each group to the control group using ANOVA, with a p-value of 0.05 used as the significance threshold as conventional. TMR: transmyocardial revascularization, PRP: platelet-rich plasma.

Figure 3. Clinical characteristics of the four study groups.

(A) Society of Thoracic Surgeons (STS) risk score; (B) preoperative left ventricular ejection fraction (LVEF); (C) preoperative global longitudinal strain (GLS). All four groups were similar in terms of their STS risk score, preoperative LVEF, and preoperative GLS. Statistical comparisons were undertaken by comparing each group to the control group using ANOVA, with a p-value of 0.05 used as the significance threshold as conventional. TMR: transmyocardial revascularization, PRP: platelet-rich plasma.

Figure 4. Comorbidities in each of the four study groups.

(A) Body mass index; (B) hypertension; (C) diabetes mellitus; (D) previous stenting; (E) hyperlipidemia; (F) preoperative intra-aortic balloon pump use. All four groups were generally similar in terms of their comorbidities. The only significant difference was a significantly greater proportion of patients in the TMR-only group with hyperlipidemia compared to controls. Statistical comparisons were undertaken by comparing each group to the control group using ANOVA, with a p-value of 0.05 used as the significance threshold as conventional. BMI: body mass index, IABP: intra-aortic balloon pump, TMR: transmyocardial revascularization, PRP: platelet-rich plasma.

Figure 5. Postoperative LVEF was similar between groups.

While differences in postoperative left ventricular ejection fraction (LVEF) between groups did not quite reach statistical significance, there was a trend toward a better LVEF in the TMR+PRP and TMR-only groups compared to the control. There was a trend towards a lower LVEF in the PRP-only group. Statistical comparisons were undertaken by comparing each group to the control group using ANOVA, with a p-value of 0.05 used as the significance threshold as conventional. TMR: transmyocardial revascularization, PRP: platelet-rich plasma.

Figure 6. A significantly improved GLS was seen at one year in the TMR+PRP group.

(A) Left ventricular ejection fraction (LVEF) at one year; (B) global longitudinal strain (GLS) at one year. There was a significantly improved GLS in the TMR+PRP group measured using speckle tracking echocardiography at one year postoperatively. Left ventricular ejection fraction (LVEF) at one year was similar between groups. Statistical comparisons were undertaken by comparing each group to the control group using ANOVA, with a p-value of 0.05 used as the significance threshold as conventional. TMR: transmyocardial revascularization, PRP: platelet-rich plasma.

Figure 7. Adverse events across the four study groups.

(A) Postoperative atrial fibrillation (POAF); (B) acute kidney injury as per KDIGO criteria [27]; (C) continuous renal replacement therapy. A significantly greater proportion of patients in the TMR+PRP group experienced POAF than the control group. Otherwise, groups were similar in terms of these adverse outcomes. Statistical comparisons were undertaken by comparing each group to the control group using ANOVA, with a p-value of 0.05 used as the significance threshold as conventional. KDIGO: Kidney Disease Improving Global Outcomes, TMR: transmyocardial revascularization, PRP: platelet-rich plasma.