Transmyocardial Laser Revascularization Research Articles

Novel concepts in the management of angina in coronary artery disease.

Coronary artery disease remains a condition with high prevalence and detrimental effects on the quality of life of affected individuals. Its most frequent manifestation, stable angina pectoris, may be challenging to manage despite the available antianginal pharmacotherapy and adequate risk factor control, especially in subjects not amenable to revascularization. In the direction of refractory angina pectoris, several approaches have been developed over the years with varying degrees of success. Among the most recognized techniques in managing angina is enhanced external counterpulsation, which utilizes mechanical compression of the lower extremities to increase blood flow to the heart. Moving to coronary sinus reduction, it leads to an increase in coronary sinus backward pressure, ultimately augmenting myocardial blood flow redistribution to ischemic regions and ameliorating chronic angina. Clinical trial results of the above-mentioned techniques have been encouraging but are based on small sample sizes to justify their widespread application. Other interventional approaches, such as transmyocardial laser revascularization, extracorporeal shockwave myocardial revascularization, and spinal cord stimulation, have been met with either controversial or negative results, and their use is not recommended. Lastly, angiogenic therapy with targeted intramyocardial vascular endothelial growth factor injection or CD34+ cell therapy may be beneficial and warrants further investigation. In this review, we summarize the current knowledge in the field of angina management, highlighting the potential and the gaps in the existing evidence that ought to be addressed in future larger-scale, randomized studies before these techniques can be safely adapted in the clinical practice of patients with refractory angina pectoris.

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy.

We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. Eight male patients (age 62 ± 2.4years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies.

Abstract 13346: Long Term, Synergistic Benefit of Transmyocardial Laser Revascularization and Platelet Rich Plasma - Significant Improvement of Global Longitudinal Strain in Coronary Artery Bypass Graft Patients

Introduction: Transmyocardial revascularization (TMR) is a procedure designed to treat patients with end-stage coronary artery disease (CAD). TMR creates myocardial micropores which undergo endothelialization and redistribute ischemic stress, thereby improving regional wall motion. Autologous platelet rich plasma (PRP) growth factors contribute to endothelialization and neovascularization. In this study, we evaluate the effectiveness of TMR combined with PRP to improve cardiac function in patients undergoing CABG using echocardiograms. Methods: A single-center, single surgeon retrospective analysis of CABG patients was performed (2019-2021). Patients in the TMR group had ten channels (7 Watts/channel) created in the infero-lateral wall of the left ventricle (LV) and those in the PRP group had autologous PRP extract injected(1ml, without calcium) in the same area. In patients treated with both TMR and PRP, ten channels were made in the inferolateral LV with PRP extract injected in the peri-TMR zone, 5mm adjacent to the channels. Post-operative ejection fraction (EF) and global longitudinal strain (GLS) were measured using speckle tracking up to one year. Results: Fifty-two patients (71% men, mean age 66y ±9.04y) were enrolled in the study and randomized to four experimental groups: CABG only (n=16); CABG/TMR (n=17); CABG/PRP (n=10); and CABG/TMR/PRP (n=9). At one-year follow-up, patients treated with both TMR and PRP had a significant improvement in average GLS (-15.96, p= 0.02) compared to TMR alone (-13.78, p= 0.26) and PRP alone (-15.79, p= 0.08). Patients treated with TMR and PRP also had a significant rise in post-operative EF (57.78%, SD +/- 6.18) compared to TMR alone (55.0%, SD +/- 6.85) and PRP alone (49.5%, SD +/- 11.65). Conclusions: TMR with PRP extract treatment at the time of CABG confers a significant one year improvement in cardiac function as measured by LVEF and GLS. These outcome metrics highlight cardiac remodeling and can mitigate the incidence of heart failure readmissions. With further prospective trials and longer follow-up periods, concomitant adjunctive TMR with PRP extract therapy at time of CABG may have durable and significant cardiac scar remodeling benefits leading to heart recovery in CABG patients.

The impact of non-pharmacological therapies on cardiovascular outcomes in patients with refractory angina: a systematic review and meta-analysis of randomized controlled trials

Abstract Despite advances in revascularization techniques and optimal medical management, refractory angina (RFA) represents an essential group of patients where progress has stalled, and in which therapeutic approaches remain uncertain. Numerous randomized control trials have reported clinical outcomes on a variety of treatments but to date no direct outcome comparison has been made. Our aim is to investigate and compare the outcomes of these different non-pharmacological technologies in RFA, centring on major adverse cardiac events and all-cause mortality. We performed a systematic review and meta-analysis of randomized controlled trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive search was performed of PubMed, EMBASE (Excerpta Medica database),Cochrane, ClinicalTrials.gov, Google Scholar databases of randomized controlled trials, and scientific session abstracts. Studies were deemed eligible if they met the following criteria: (1) full-length publications in peer-reviewed journals; (2) evaluated non-pharmacological therapies use in patients with no further revascularization options while on optimal medical treatment; (3) patients had ongoing angina, Canadian Cardiovascular Society class II–IV; and (4) included a placebo/control arm. We calculated risk ratios for all-cause mortality, combined MACE events. We assessed heterogeneity using χ2 and I2 tests. We analysed 3292 citations with 51 randomized control trials testing 9 therapies including angiogenic proteins, stem-cell therapy, lipoprotein apheresis, coronary sinus reducer, spinal cord stimulator, percutaneous laser revascularization, shock-wave therapy, transmyocardial laser revascularization and enhanced external counter pulsation all meeting the inclusion criteria (table 1). Our analysis identified stem cell therapy as the only therapy with a reduction in all-cause mortality (Odds ratio, 0.45; CI, 0.21–1.00) (figure 1). A corresponding reduction in major adverse cardiac events (MACE) was also seen with stem cell therapy (OR 0.48: CI 0.30–0.75) alongside patients who received angiogenic proteins (OR 0.72: CI 0.55–0.93) and cardiac shockwave therapy (OR, 0.21: CI 0.10–0.46) Improvements in secondary measures of angina symptoms or frequency were seen with stem cell therapy, angiogenic proteins, coronary sinus reducer, spinal cord stimulator, shock-wave therapy, transmyocardial laser revascularization and enhanced external counterpulsation. This is the largest meta-analysis comparing outcomes of novel technologies used in refractory angina. This suggests that stem cell therapy is the only non-pharmacological therapy for RFA associated with a reduction in mortality, MACE and anginal symptoms. We propose further larger randomized control trials, to support these findings. Funding Acknowledgement Type of funding sources: None. Table 1. Randomized control trials and outcomesFigure 1. All-cause mortality forest plot

Management of refractory angina: an update.

Despite the use of anti-anginal drugs and/or percutaneous coronary interventions (PCI) or coronary artery bypass grafting, the proportion of patients with coronary artery disease who have daily or weekly angina ranges from 2% to 24%. Refractory angina refers to long-lasting symptoms (for >3 months) due to established reversible ischaemia, which cannot be controlled by escalating medical therapy with the use of 2nd- and 3rd-line pharmacological agents, bypass grafting, or stenting. While there is uncertain prognostic benefit, the treatment of refractory angina is important to improve the quality of life of the patients affected. This review focuses on conventional pharmacological approaches to treating refractory angina, including guideline directed drug combination and dosages. The symptomatic and prognostic impact of advanced and novel revascularization strategies such as chronic total occlusion PCI, transmyocardial laser revascularization, coronary sinus occlusion, radiation therapy for recurrent restenosis, and spinal cord stimulation are also covered and recommendations of the 2019 ESC Guidelines on the Diagnosis and Management of Chronic Coronary Syndromes discussed. Finally, the potential clinical use of current angiogenetic and stem cell therapies in reducing ischaemia and/or pain is evaluated.

A DECADE OF EXPERIENCE IN APPLICATION OF TRANSMYOCARDIAL LASER REVASCULARIZATION IN COMBINATION WITH AORTOCORONARY SHUNTING

Objective: to study the security and the effect of transmyocardial laser revascularization in combination with aortocoronary shunting in patience with diffuse coronary artery disease.Materials and methods: the study compared the results of surgical treatment in patients with diffuse distal coronary artery disease in the period from 2007 to 2013. Patients were divided into two groups, the first group consisted of patients who underwent CABG in combination with TMLR (n-60), the second group includes patients who underwent isolated CABG (n-46). According to the initial demographic data and comorbidity, the groups were not significantly different from each other. Subsequent observation (on average 7, 5±0, 9 years) included rating of survival and return of angina. Results: remote mortality during the observation period in the first group was 7, 6 % (n = 4), and in the second group — 18, 9 % (n = 7). In both groups the functional class of angina pectoris significantly decreased, however, in the first group this tendency was more expressed (exertional angina I EF in the CABG + TMLR group have 54 (90 %) patients, in the second group — 33 (71,7 %), p = 0,02. Conclusions: transmyocardial laser revascularization in combination with aortocoronary shunting in high-risk patients with diffuse atherosclerotic lesions of the coronary arteries contributed to an increase in exercise tolerance, reduced symptoms, and provided an acceptable quality of life in the long term.

Long-term results of isolated transmyocardial laser revascularization in combination with the intramyocardial autologous bone marrow stem cells injection.

To evaluate the long-term results of TMLR using a CO2 laser in combination with intramyocardial injection of ABMSC as an isolated procedure in patients with the end-stage coronary artery disease, the study included 20 patients (90% male), with a mean age of 58.4 ± 8.7 years. To assess the long-term results, patients were examined in a hospital. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Angina Questionnaire (SAQ) were used. The evolution of laboratory and instrumental indices, as well as medical therapy, was assessed. The end points of the study were death, acute myocardial infarction (AMI), repeated myocardial revascularization, recurrent hospitalizations due to coronary artery disease, and stroke. The changes in angina functional class were also evaluated. The median of follow-up period was 54 (36; 83) months, that is, 4.5 years. The analysis of the evolution of echocardiographic data showed the absence of statistically significant changes in the following parameters: left ventricular end-diastolic diameter (EDD) (p = 0.967), end-systolic diameter (ESD) (p = 0.204), end-diastolic volume (EDV) (p = 0.852), end-systolic volume (ESV) (p = 0.125), and left ventricular ejection fraction (LVEF) (p = 0.120). The patients continued to regularly take the main groups of medications. Nitrate consumption was significantly reduced (p < 0.001). Significant positive dynamics were observed in the changes in angina functional class. At the baseline, all patients had angina III FC, in the long term, 3 patients had II FC, 11 patients had I FC, and 6 patients had no angina. Clinical outcomes (mortality, recurrent myocardial infarction, stroke) were absent during the follow-up period. There were two cases of repeated myocardial revascularization. Regression analysis revealed that SYNTAX score was associated with the clinical outcome "repeated revascularization." TMLR in combination with intramyocardial injection of ABMSC is a safe method to achieve a statistically significant antianginal effect and reduce the need for "nitrates," which in turn improves the quality of life and reduces the frequency of hospitalizations due to coronary artery disease. These results can be achieved with strict adherence to the certain indications for the intervention.

NON-CONVENTIONAL APPROACHES FOR THE MANAGEMENT OF ANGINA

Angina is usually classified as a symptom of an underlying cardiovasculardisease which is one of the most common disorder that is affecting the human lifenow a days. It is presented as a throbbing chest pain that can radiate to left armand back due to ischemia of major vessel supplying blood to heart. Several drugclasses and their combination has long been used to treat angina for e.g. Nitrates,Nitrites, Calcium channel blockers, Beta blockers and sodium channel blockersto improve the demand vs supply ratio of oxygen so that the heart muscles canperform its function effectively. The increasing prevalence of disease andresulting resistance to conventional therapy has urged scientists to find otherways that can help in the management of this disease. Cardiovascular andconsequently angina is thus the focus of many studies. In this review a number ofstrategies and their associated mechanisms has been discussed which includeLife style modification, Yoga, Acupuncture therapy, Herbal treatment , L-arginine,L-carnitine, Omega 3 fatty acids, Gene therapy, Cell therapy, Chinese Medicine,and Interventions like Spinal cord Stimulation, Percutaneous coronaryintervention, Enhance external counter pulsation, Extracorporeal shockwavemyocardial revascularization, Transmyocardial laser revascularization,transcutaneous electrical nerve stimulation, percutaneous retrograde coronarysinus perfusion. Coronary sinus perfusion, Coronary sinus reducer, Videothoracoscopic sympathectomy (VTSY) may help in short term and long-termmanagement of angina

Impact of Nd : YAG laser radiation (λ = 1.44 mm) on myocardial tissue in the treatment of coronary heart disease by transmyocardial laser revascularisation

We have studied the impact of Nd : YAG laser radiation with a wavelength of λ = 1.44 μm on the myocardial tissue for the formation of channels in the treatment of coronary heart disease by transmyocardial laser revascularisation (TMLR). The mechanism of perforation of the myocardial tissue by a laser pulse is presented and an experimental setup for TMLR is developed. In experiments on biological objects, the optimal parameters of radiation energy and duration necessary for the formation of channels of a given size in a single laser pulse are determined. The exposure regime ensures the adequate character of myocardial tissue destruction, assessed by such criteria as the perforation force, exposure energy, size of the coagulation zone, and level of carbonisation.

An Experimental Apparatus for Transmyocardial Laser Revascularization Based on an Nd:YAG Laser

We present here the results obtained during the development of an experimental apparatus for transmyocardial laser revascularization based on an Nd:YAG laser. Use of laser irradiation with a wavelength of 1.44 μm was shown to be effective in producing targeted angiogenesis in transmyocardial laser revascularization in experimental studies using a model of ischemic myocardium. The optimum regimes for pulsed Nd:YAG laser irradiation of the myocardium with thermal tissue damage were established. Morphological changes in the transmyocardial laser channels in pig myocardium were studied. The objective of the experiments was to confirm the efficacy of using this apparatus for transmyocardial laser revascularization with an Nd:YAG laser for the treatment of patients with diffuse lesions to the coronary arteries.

Refractory Angina: the Current State of Mechanical Therapies.

Refractory angina (RA), which is characterized by tissue ischemia along with neurological, mitochondrial, and psychogenic dysfunction, is becoming a major cause of morbidity in patients with advanced coronary artery disease. In this review, we discuss in detail the invasive mechanical non-cell therapy-based options, the evidence behind these therapies, and future trends. There is extensive ongoing research in the areas of spinal-cord stimulation, transmyocardial laser revascularization, sympathectomy, angiogenesis, and other non-cell-based therapies to explore the best therapy for refractory angina. There is conflicting data in the literature suggesting subjective improvement in angina, but very few studies boast improvement in core objective parameters such as myocardial blood flow, survival, or rehospitalizations. Patients with refractory angina are a complex group of patients that need novel approaches to help alleviate their symptoms and reduce mortality. A carefully selected sequence of therapies may provide the best results in this patient population.

Отдаленные результаты операций изолированной трансмиокардиальной лазерной реваскуляризации в сочетании с интрамиокардиальным введением аутологичных стволовых клеток костного мозга

Введение. В настоящее время во всем мире активно внедряются альтернативные методы лечения ишемической болезни сердца (ИБС) и используются в ситуациях, когда не представляется возможным выполнить прямую реваскуляризацию миокарда. Среди них трансмиокардиальная лазерная реваскуляризация (ТМЛР), введение аутологичных стволовых клеток костного мозга (АСККМ). Чтобы достичь «синергизма» ТМЛР с интрамиокардиальным введением АСККМ, оба метода комбинировали.

Is there RCT evidence to support the use of transmyocardial laser revascularization compared with medical therapy for the treatment of refractory angina?

Is there RCT evidence to support the use of transmyocardial laser revascularization compared with medical therapy for the treatment of refractory angina?

Experimental Studies of the Efficacy of Transmyocardial Laser Revascularization Using an Erbium Laser

Results obtained using an erbium laser to produce directed angiogenesis in transmyocardial laser revascularization in experiments using an animal model of chronically ischemic myocardium are presented. An assessment of the efficacy of using the erbium laser to produce targeted angiogenesis is presented. The optimum operating regimes for erbium laser pulse irradiation of the myocardium, taking account of thermal tissue lesions, are identified. Morphological changes are investigated and morphometric analysis in tissues in the area of the transmyocardial laser channels are analyzed in a model of chronic ischemic heart disease (IHD) in dogs. Studies were performed for subsequent development and introduction of the new method into clinical practice in patients with IHD with diffuse coronary artery lesions.

EP13 EVOLUTIONARY AND CYCLICAL CHANGES IN CARDIAC SURGERY

Abstract Background and aim: The analysis of modern models and criteria discloses that current cardiac surgery often recalls the past. The aim of this study is to investigate whether historical knowledge is an important tool for research in aortic valve surgery and myocardial revascularization. Methods: PubMed, Scopus and Sciencedirect analysis of past and current literature were adopted to compare previous and current ideas. Results: In 1922, Graham and Allen introduced a cardioscope and a knife through the subclavian artery, or the left ventricular apex, to divide calcified aortic valve leaflets. This technique is a precursor of TAVI. The concept of sutureless prosthesis existed in the fifties and sixties. Hufnagel routinely implanted sutureless prostheses in the descending thoracic aorta to treat aortic insufficiency. The sutureless Magovern-Cromie valve has been implanted in orthotropic position from 1964 onward. The Sen's technique of trans-ventricular tunnels is a precursor of laser trans-myocardial revascularization. The Italian technique of internal mammary arteries ligature to treat angina pectoris, dating back to 1939 (Fieschi), and to the 50’ (Battezzati) was rediscovered, following 50 years of silence, in 2010. Endovascular occlusion of the mammary arteries by embolization has been suggested to treat patients suffering from angina not amenable to conventional revascularization techniques. Conclusions: Knowledge of old ideas and experiments, released from the technological constraints of their time, can be useful in current research. Ingenious theories that have fallen by the wayside can be brought back and explored again. History is a cycle. Heart valve surgery and myocardial revascularization are no exception.

Ten-year follow-up after combined coronary artery bypass grafting and transmyocardial laser revascularization in patients with disseminated coronary atherosclerosis

Coronary artery disease involving heavily calcified lesions has been associated with worse short- and long-term outcomes including increased mortality. This paper aims to evaluate long-term survival benefit when CABG + transmyocardial laser revascularization (TMLR) are performed on the hearts of patients with disseminated coronary atherosclerosis (DCA). This novel retrospective study was conducted between 1997 and 2002 and followed 86 patients with ischemic heart disease and severe DCA who underwent TMLR using a Holmium:YAG laser and/or CABG. There were 46 patients who had CABG plus TMLR on at least one heart wall (“combined therapy group”) and 40 patients who had CABG or TMLR separately on at least one heart wall (“single therapy group”). For the whole group, actuarial survival at 10 years was 78.3% in the combined group compared to 72.5% in the single therapy group (p = 0.535). Ten-year survival in the combined vs. single therapy group for the anterior heart walls was 100 vs. 72.2% (p = 0.027). For the lateral and posterior heart walls were 73.7 vs. 73.3% (p = 0.97) and 84.2 vs. 72% (p = 0.27), respectively. Kaplan-Meier survival analysis showed benefit only for the anterior heart wall (F Cox test, p = 0.103). Single therapy procedures on all heart walls (odds ratio 1.736, p = 0.264) or on the anterior heart wall only (odds ratio 3.286, p = 0.279) were found to be predictors of 10-year late mortality. Combined therapy (TMLR + CABG) provides benefit for perioperative mortality and long-term survival only when provided on the anterior heart wall. For patients with disseminated coronary atherosclerosis, cardiac mortality was found to be increased when followed up 6 years later, regardless of the therapy applied.

Midterm outcomes of transmyocardial laser revascularization with intramyocardial injection of adipose derived stromal cells for severe refractory angina.

IntroductionRefractory angina has limited effective therapeutic options and often contributes to frequent hospitalizations, morbidity and impaired quality of life.AimWe sought to examine midterm results of a bio-interventional therapy combining transmyocardial laser revascularization (TMLR) and intramyocardial injection of adipose derived stem cells (ADSC) in patients with refractory angina not amenable to percutaneous or surgical revascularization.Material and methodsWe included 15 patients with severe refractory angina and anterior wall ischemia who were ineligible for revascularization strategies. Adipose tissue was harvested and purified, giving the stem cell concentrate. All patients underwent left anterior thoracotomy and TMLR using a low-powered holmium : yttrium–aluminum–garnet laser and intramyocardial injection of ADSC using a combined delivery system.ResultsNo deaths or major adverse cardiovascular or cerebrovascular events were observed in the 6-month follow-up. Mean ejection fraction increased from 35% to 38%, and mean Canadian Cardiovascular Society Angina Score decreased from 3.2 to 1.4, with decreased necessity of nitrate usage. Seventy-three percent of patients reported health improvement particularly regarding general health and bodily pain. Improvement in endocardial movement, myocardial thickening and stroke volume index (35.26 to 46.23 ml/m2) on cardiac magnetic resonance imaging (MRI) was observed in 3 patients who had repeat CMR imaging after 6 months.ConclusionsOur study suggested that interventional therapy combining TMLR with intramyocardial implantation of ADSC may reduce symptoms and improve quality of life in patients with refractory angina. These early findings need further validation in large scale randomized controlled trials.

Влияние трансмиокардиальной лазерной реваскуляризации на ангинальные симптомы и клинический эффект у пациентов с неполной хирургической реваскуляризацией.

Цель. Оценить в отдаленном периоде влияние трансмиокардиальной лазерной реваскуляризации (ТМЛР) на ангинальные симптомы и клинические результаты у пациентов, которым невозможно выполнить полную реваскуляризацию методом аортокоронарного шунтирования (АКШ).

Transmyocardial laser revascularization combined with coronary artery bypass grafting in patients with severe forms of ischemic heart disease

Transmyocardial laser revascularization combined with coronary artery bypass grafting in patients with severe forms of ischemic heart disease