Percutaneous Laser Revascularization Research Articles

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

Effectiveness of percutaneous laser revascularization therapy for refractory angina.

Refractory angina is a debilitating disease characterized by persistent cardiac pain resistant to all conventional treatments for coronary artery disease. Percutaneous myocardial laser revascularization (PMLR) has been proposed to improve symptoms in these patients. We used meta-analysis to assess the effectiveness of PMLR versus optimal medical therapy for improving angina symptoms, health-related quality of life (HRQL), and exercise performance; the impact on all-cause mortality was also examined. Seven trials, involving a total of 1,213 participants were included. Our primary analyses showed that at 12-month follow-up, those who had received PMLR had ≥2 Canadian Cardiovascular Society class angina symptom reductions, OR 2.13 (95% CI, 1.22 to 3.73), as well as improvements in aspects of HRQL including angina frequency, SMD = 0.29 (95% CI, 0.05 to 0.52), disease perception, SMD = 0.37 (95% CI, 0.14 to 0.61), and physical limitations, SMD = 0.29 (95% CI, 0.05 to 0.53). PMLR had no significant impact on all-cause mortality. Our secondary analyses, in which we considered data from one trial that featured a higher-dose laser group, yielded no significant overall impact of PMLR across outcomes. While PMLR may be effective for improving angina symptoms and related burden, further work is needed to clarify appropriate dose and impact on disease-specific mortality and adverse cardiac events.

The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium: A pilot study

Background Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium. Methods A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies. Results A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed. Hibernating myocardium was demonstrated 4 weeks after ameroid placement by DSE. Coronary angiography demonstrated a discrete 90%stenosis in the proximal LAD at the site of ameroid constrictor placement without evidence of collaterals. Using PMR, 17 bursts were successfully delivered to the anterior wall distal to the ameroid constrictor. Four weeks after PMR, there was improvement in wall motion function in the region distal to the ameroid placement by echocardiography. Histopathologic analysis demonstrated the absence of myocardial infarction in the anterior wall distal to the ameroid constrictor. Conclusions The performance of PMR in a porcine model of hibernating myocardium is feasible and is associated with an improvement regional wall motion function after 4 weeks.

Alternative therapeutic strategies for patients with severe end-stage coronary artery disease not amenable to conventional revascularization.

Although there have been remarkable advances in medical therapy, percutaneous coronary interventions, and coronary artery bypass graft surgery, complete revascularization remains a challenge given the more complex coronary artery disease prevalent in contemporary practice. The lack of donors for cardiac transplantation will fuel the search for effective alternative strategies for dealing with patients with severe ischemic heart disease not amenable to conventional revascularization techniques. Percutaneous laser revascularization clearly diminishes anginal symptoms; however, the blinded trials have provided conflicting results, with one study showing a definite decrease in angina and another suggesting that the placebo effect may play a major role in this modality. Similarly, surgical transmyocardial laser revascularization is limited by the lack of consistent improvement in objective measurements of ischemia and the potential confounding mechanisms of denervation and the placebo effect, and thus should be reserved for only the most highly selected patients. Although enhanced external counterpulsation is associated with an improvement in anginal symptoms and exercise tolerance, this modality is limited by its availability, tolerability, and rigid exclusion criteria. Of the alternative strategies available, therapeutic angiogenesis holds the most promise. However, the long-term results of ongoing randomized clinical trials require further scrutiny. Novel methods for vascular reconstruction are evolving techniques, but should be viewed currently as mainly experimental methods. The common goals of these new treatment options would be to reduce symptoms, decrease morbidity, and potentially improve mortality by reducing ischemia through favorably impacting myocardial oxygen supply and demand. The optimal management of patients with severe end-stage coronary artery disease not amenable to conventional revascularization techniques will continue to remain a challenge for the clinician and will be the main focus of basic cardiovascular research and clinical trials in the new millennium.

Do transmyocardial and percutaneous laser revascularization induce silent ischemia? An assessment by exercise testing

Background Transmyocardial and percutaneous laser revascularization (TMR, PTMR) may reduce angina and increase exercise tolerance in otherwise untreatable angina patients, although the mechanism is unknown and the placebo effect may be significant. One other proposed mechanism is cardiac denervation leading to silent ischemia. Methods Electrocardiograms obtained during symptom-limited exercise (ETT, modified Bruce protocol) at baseline and 12 months were analyzed (blinded core laboratory) from 182 patients randomized to TMR (n = 92) or medical therapy alone (MEDTMR, n = 90) and 219 patients randomized to PTMR (n = 109) or medical therapy alone (MEDPTMR, n = 110). Results Exercise duration increased 1 year after TMR or PTMR relative to medically treated patients (6.8 ± 3.4 min vs 8.6 ± 3.5 min for TMR; 7.3 ± 3.1 min vs 9.1 ± 3.6 min for PTMR, P <.05). At baseline, 20% of TMR and MEDTMR subjects had ST depression >1.0 mm, >80% had angina during exercise, but only 3% had ST changes without chest pain (silent ischemia). This did not change after TMR. In the PTMR group, more subjects exercised to >1.0 mm ST depression (from 17% to 34%, P <.05), with no change in MEDPTMR, but the proportion with silent ischemia did not change in either group. Conclusion Exercise tolerance improved after TMR and after PTMR. Relative to PTMR, TMR more effectively suppressed pain during exercise and ischemic ST depression. However, neither TMR nor PTMR induced significant silent ischemia. These results suggest that denervation may not be a significant factor contributing to angina relief after these procedures. The contribution of the placebo effect was not determined by these results. (Am Heart J 2002;143:1052-7.)

Changes in myocardial perfusion after catheter-based percutaneous laser revascularisation.

This study investigated the effect of percutaneous laser revascularisation (PMR) on regional myocardial blood flow. PMR is a new therapeutic modality for patients suffering from angina pectoris due to coronary artery disease (CAD) that is not amenable to revascularisation. Initial clinical studies discovered reduced angina pectoris and increased exercise capacity after PMR. There are no previous clinical studies reporting the impact of PMR on perfusion. Thirty-six patients with end-stage CAD underwent thallium-201 single-photon emission tomography studies on four different occasions: immediately before PMR and 3, 6 and 12 months following PMR. Each study consisted of pharmacological stress and rest scintigraphy. Semiquantitative evaluation was performed by use of 14 standardised wall segments which were classified (a) according to the localisation of the PMR target region into treated segments, segments adjacent to the treated area and non-treated segments and (b) according to the pre-therapeutic local perfusion into four groups: no (0), slight (I), moderate (II) or severe (III) perfusion deficit. At stress in treated segments of groups II and III local scintigraphic count densities increased from 60.1% and 34.7% at baseline to 65.3% and 48.3% after 12 months (P<0.05) while they decreased in segments of group 0 from 94.2% to 85.7% (P<0.05). In rest studies no changes occurred. Thus, the local rest-stress differences within the target areas become smaller after PMR. In the PMR target area but not in the nontreated area an improvement in regional myocardial flow reserve occurs in wall segments with initially severely or moderately reduced stress perfusion. This effect is consistent with the clinical improvement after PMR.

188 Percutaneous laser revascularization improves resting ejection fraction as determined by contrast echocardiography in patients with refractory angina

188 Percutaneous laser revascularization improves resting ejection fraction as determined by contrast echocardiography in patients with refractory angina

188 Percutaneous laser revascularization improves resting ejection fraction as determined by contrast echocardiography in patients with refractory angina

188 Percutaneous laser revascularization improves resting ejection fraction as determined by contrast echocardiography in patients with refractory angina

Feasibility and safety of percutaneous laser revascularization using the Biosense system in porcine hearts.

Direct myocardial revascularization (DMR) is being explored to improve symptoms in patients with refractory ischemic coronary syndromes. This study assessed the safety and feasibility of percutaneous DMR using the Biosense non-fluoroscopic navigation system (incorporating the holmium : yttrium aluminium garnet laser) in pig hearts. Twenty pigs underwent left ventricular mapping using the Biosense system, followed by percutaneous DMR with a holmium : yttrium aluminium garnet laser at 2 J x 1 pulse, and were sacrificed acutely (n = 5), at 24 h (n = 5), and at 3 weeks (n = 10) after the DMR procedure. The hearts were examined grossly and microscopically. Serial creatine kinase-MB level was measured up to 24 h. There were no procedural complications. Animals received 13 +/- 2 channels in 19 +/- 7 min. The catheter was able to reach all regions, including the septum. There was no increase in creatine kinase-MB level up to 24 h. One animal died within an hour of the procedure. There was one sealed perforation into the subepicardial fat as a result of same site laser activation. Histologic evaluation in the acute and 24 h groups revealed laser channels which were 3.6 +/- 2.2 mm long, 1.5 +/- 0.7 mm wide, with an entry angle of 73 +/- 12 degrees. Channels were filled with platelet thrombi acutely and were surrounded by well-defined rims of thermal coagulation and an 'impact zone' of viable myocardium; at 3 weeks, no channels remained patent and they had been replaced by well-healed granulation tissue. It is feasible and safe to perform percutaneous DMR with the Biosense system and the channels created with the chosen laser parameters are rapidly sealed with platelet thrombi and at 3 weeks are replaced by well-healed granulation tissue.