Title: Improved myocardial perfusion after transmyocardial laser revascularization in a patient with microvascular coronary artery disease.
Authors: Oskui PM, Mayeda GS, Burstein S, Gheissari A, French WJ, Thomas J, Kloner RA.
Publication: Lancet. SAGE Open Med Case Rep. 2014 Mar 4
We report the case of a 59-year-old woman who presented with symptoms of angina that was refractory to medical management. Although her cardiac catheterization revealed microvascular coronary artery disease, her symptoms were refractory to optimal medical management that included ranolazine. After undergoing transmyocardial revascularization, her myocardial ischemia completely resolved and her symptoms dramatically improved. This case suggests that combination of ranolazine and transmyocardial revascularization can be applied to patients with microvascular coronary artery disease.
Title: Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.
Authors: Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprielian R, Malik IS, Nijjer SS, Petraco R, Cook C, Ahmad Y, Howard J, Baker C, Sharp A, Gerber R, Talwar S, Assomull R, Mayet J, Wensel R, Collier D, Shun-Shin M, Thom SA, Davies JE, Francis DP; ORBITA investigators.
Publication: Lancet. 2018 Jan 6;391(10115):31-40.
Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy.
ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593.
ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group.
In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.
Title: Transmyocardial revascularization: 5-year follow-up of a prospective, randomized multicenter trial.
Authors: Allen KB, Dowling RD, Angell WW, Gangahar DM, Fudge TL, Richenbacher W, Selinger SL, Petracek MR, Murphy D.
Publication: Ann Thorac Surg. 2004 Apr;77(4):1228-34.
In prospective randomized trials at 1 year, transmyocardial revascularization (TMR) provided superior relief of angina, decreased rehospitalizations, and improved exercise times. We evaluated 5-year mortality and angina class in “no-option” patients with diffuse coronary artery disease randomized to TMR or continued medical management.
Two hundred twelve patients with refractory class IV angina who were not candidates for conventional therapy were randomized to receive holmium:yttrium-aluminum-garnet TMR (n = 100) or continued medical management (n = 112) at nine centers. Follow-up included all-cause mortality along with angina class assessment by blinded evaluators. Mean follow-up was 5.7 +/- 0.8 years.
Mean angina scores for TMR patients were 4.0 +/- 0.0 at baseline, 1.5 +/- 1.4 at 1 year, and 1.2 +/- 1.1 at a mean of 5 years (p < 0.001). After an average of 5 years, a significantly greater proportion of TMR than medical management patients experienced two or more class improvement in angina (88% versus 44%; p < 0.001). Kaplan-Meier intention-to-treat survival at 5 years was 65% versus 52% (TMR versus medical management; p = 0.05). Cumulative hazard curves demonstrated a significantly reduced risk of late death for TMR patients; average annual mortality beyond 1 year was 8% versus 13% (TMR versus medical management; p = 0.03).
Five-year follow-up of prospectively randomized, no-option class IV angina patients demonstrated significantly increased Kaplan-Meier survival in patients randomized to TMR. The significant angina relief observed 12 months after sole therapy TMR was sustained long term and continued to be superior to that observed for patients maintained on continued medical management alone.
Title: Adjunctive transmyocardial revascularization: five-year follow-up of a prospective, randomized trial.
Authors: Allen KB, Dowling RD, Schuch DR, Pfeffer TA, Marra S, Lefrak EA, Fudge TL, Mostovych M, Szentpetery S, Saha SP, Murphy D, Dennis H.
Publication: Ann Thorac Surg. 2004 Aug;78(2):458-65; discussion 458-65.
In a prospective, randomized trial involving 263 patients who would be incompletely revascularized by coronary artery bypass grafting (CABG) alone, CABG plus transmyocardial revascularization (CABG/TMR) provided an early mortality benefit with similar angina relief compared with CABG alone at 1 year. We evaluated the long-term outcome of patients randomized to CABG/TMR or CABG alone.
Thirteen centers that enrolled 83% (218/263) of the patients in the original trial participated in this longitudinal study. Between 1996 and 1998, these centers randomized 218 patients who would be incompletely revascularized by CABG alone because of diffusely diseased target vessels to either holmium:yttrium-aluminum-garnet (holmium:YAG) CABG/TMR (n = 110) or CABG alone (n = 108). Baseline demographics and operative characteristics were similar between groups. Follow-up (mean 5.0 +/- 1.7 years) included survival and blinded angina class assessment.
At this 5-year follow-up both groups experienced significant angina improvement from baseline, however, the CABG/TMR group had a lower mean angina score (0.4 +/- 0.7 vs 0.7 +/- 1.1, p = 0.05), a significantly lower proportion of patients with severe angina (class III/IV: 0% [0/68] vs 10% [6/60], p = 0.009), and a trend towards greater number of angina-free patients (78% [53/68] vs 63% [38/60], p = 0.08), compared with CABG alone patients. Kaplan-Meier survival at 6 years was similar between CABG/TMR and CABG alone patients (76% vs 80%, p = 0.90).
Five-year follow-up of prospectively randomized patients who would be incompletely revascularized because of diffuse coronary artery disease indicates that the addition of TMR to conventional CABG provides superior angina relief compared to CABG alone.
Title: Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina.
Authors: Allen KB, Dowling RD, Fudge TL, Schoettle GP, Selinger SL, Gangahar DM, Angell WW, Petracek MR, Shaar CJ, O’Neill WW.
Publication: N Engl J Med. 1999 Sep 30;341(14):1029-36
Transmyocardial revascularization involves the creation of channels in the myocardium with a laser to relieve angina. We compared the safety and efficacy of transmyocardial revascularization performed with a holmium laser with those of medical therapy in patients with refractory class IV angina (according to the criteria of the Canadian Cardiovascular Society).
In a prospective study conducted between March 1996 and July 1998 at 18 centers, 275 patients with medically refractory class IV angina and coronary disease that could not be treated with percutaneous or surgical revascularization were randomly assigned to receive transmyocardial revascularization followed by continued medical therapy (132 patients) or medical therapy alone (143 patients).
After one year of follow-up, 76 percent of the patients who had undergone transmyocardial revascularization had improvement in angina (a reduction of two or more classes), as compared with 32 percent of the patients who received medical therapy alone (P<0.001). Kaplan-Meier survival estimates at one year (based on an intention-to-treat analysis) were similar for the patients assigned to undergo transmyocardial revascularization and those assigned to receive medical therapy alone (84 percent and 89 percent, respectively; P=0.23). At one year, the patients in the transmyocardial-revascularization group had a significantly higher rate of survival free of cardiac events (54 percent, vs. 31 percent in the medical-therapy group; P<0.001), a significantly higher rate of freedom from treatment failure (73 percent vs. 47 percent, P<0.001), and a significantly higher rate of freedom from cardiac-related rehospitalization (61 percent vs. 33 percent, P<0.001). Exercise tolerance and quality-of-life scores were also significantly higher in the transmyocardial-revascularization group than in the medical-therapy group (exercise tolerance, 5.0 MET [metabolic equivalent] vs. 3.9 MET; P=0.05); quality-of-life score, 21 vs. 12; P=0.003). However, there were no differences in myocardial perfusion between the two groups, as assessed by thallium scanning.
Patients with refractory angina who underwent transmyocardial revascularization and received continued medical therapy, as compared with similar patients who received medical therapy alone, had a significantly better outcome with respect to improvement in angina, survival free of cardiac events, freedom from treatment failure, and freedom from cardiac-related rehospitalization.
Title: Transmyocardial Laser Revascularization Enhances Blood Flow within Bypass Grafts.
Authors: Tran R, Brazio PS, Kallam S, Gu J, Poston RS.
Publication: Innovations (Phila). 2007 Sep;2(5):226-30.
Early benefits from transmyocardial laser revascularization (TMR) may be related to acute sympathetic denervation. This study hypothesized that TMR as an adjunct to off-pump coronary artery bypass (OPCAB) would improve myocardial runoff in the TMR-treated regions and increase graft flow.
Graft blood flow was measured in 145 consecutive OPCAB patients. In patients with graft flow <40 mL/min (n = 25), the myocardial region served by the graft was treated with TMR. Blood flow was reassessed 10 minutes after TMR and compared with graft flow in the nontreated regions. Postoperative outcomes, transcardiac thrombin production, coagulation activation, myocardial, and inflammatory markers were assessed. A control group not treated with TMR (n = 14) was selected with similar graft flows and other baseline characteristics.
Risk factors, comorbidities, and preoperative medications were similar in all groups. TMR led to a 48% increase in bypass graft flow in 12 patients, but no significant change in flow in the remainder (n = 13). The control group also showed no change in graft flow measured during the same time-points. Compared with those that did not respond to TMR, responders showed a greater drop in pH during warm ischemia caused by distal anastomoses during OPCAB and significantly higher transcardiac gradients of F1.2, IL-8, TNFα, and VCAM.
TMR acutely improves venous bypass graft flow in regions with more severe myocardial acidosis and inflammation during and after OPCAB. Acute sympathetic denervation after TMR may provide mechanistic insight into the early clinical benefits of TMR as an adjunct to OPCAB.
Title: Patients with coronary artery disease not amenable to traditional revascularization: prevalence and 3-year mortality.
Authors: Williams B, Menon M, Satran D, Hayward D, Hodges JS, Burke MN, Johnson RK, Poulose AK, Traverse JH, Henry TD.
Publication: Catheter Cardiovasc Interv. 2010 May 1;75(6):886-91.
To determine the contemporary prevalence of and mortality in patients with coronary artery disease (CAD) not amenable to revascularization.
A growing number of patients have severe CAD with ongoing angina despite optimal medical therapy which is not amenable to traditional revascularization. Limited data exist on contemporary prevalence and outcome for these patients.
Clinical and angiographic data were reviewed for 493 consecutive patients undergoing coronary angiography and revascularization if indicated. Patients were categorized into six groups: (1) normal coronary arteries, (2) CAD <70%, (3) CAD >70% with complete revascularization by percutaneous intervention or coronary artery bypass grafting, (4) CAD >70% with partial revascularization, (5) CAD >70% treated medically, and (6) CAD >70% on optimal medical therapy with no revascularization option. All-cause mortality at 3 years was determined.
Prevalence for groups 1-6 was 14.8, 19.5, 36.9, 12.8, 9.3, and 6.7%, respectively. Three-year mortality increased with angiographic severity of CAD: 2.7, 6.3, 8.2, 12.7, 17.4, and 15.2%, respectively. Patients with incomplete revascularization (groups 4-6, n = 142) had higher mortality than completely revascularized patients (groups 1-3, n = 351): 14.8 vs. 6.6% (P = 0.004).
In a contemporary series of patients undergoing coronary angiography, 28.8% (142/493) of patients had significant CAD and did not undergo complete revascularization, including 12.8% partially revascularized, 9.3% managed medically, and 6.7% with “no-option.” These patients had higher mortality at 3 years (14.8 vs. 6.6%, P = 0.004) when compared with completely revascularized patients.
Title: Improved patient outcomes when transmyocardial revascularization is used as adjunctive revascularization.
Authors: Wehberg KE1, Julian JS, Todd JC 3rd, Ogburn N, Klopp E, Buchness M.
Publication: Heart Surg Forum. 2003;6(5):328-30.
Transmyocardial revascularization (TMR) has been recently used to treat patients with angina for whom angioplasty/stenting and/or coronary artery bypass grafting (CABG) is no longer an option.
A retrospective review of 255 consecutive patients who required CABG was done. Group 1 patients (n = 219) underwent complete revascularization with CABG alone. Group 2 patients (n = 36) received CABG plus TMR. TMR was performed in regions of nongraftable coronary targets. Indications for surgery in both groups were Canadian Cardiovascular Society angina scores III or IV and an ejection fraction > or = 30%. Exclusion criteria were an emergency procedure within 12 hours, unstable angina, or an acute myocardial infarction within 72 hours. Thirty-day outcomes of the two groups were compared. The means +/- SD of patient ages (63.3 +/- 1.6 years versus 65.4 +/- 1.4 years) and ejection fractions (51.6% +/- 0.9% versus 48.5% +/- 1.6%) were similar for the two groups.
The number of grafts performed and operating room times for the two groups were similar (3.1 +/- 0.1 versus 2.9 +/- 0.1 and 276.7 +/- 4.4 minutes versus 272.3 +/- 10.7 minutes, respectively). Intensive care unit times and lengths of stay (emergency room to discharge) were significantly shorter in the CABG plus TMR group (2.1 +/- 0.2 days versus 1.6 +/- 0.2 days [P < .001] and 8.2 +/- 0.4 days versus 7.1 +/-0.6 days [P < .001], respectively). The 30-day readmission rate was lower in the CABG plus TMR group (7.8% versus 2.8%; P < .5). The frequency of atrial fibrillation was also significantly lower in the CABG plus TMR group (37.4% versus 16.7%; P < .025). Major adverse outcomes, such as reoperation for bleeding, respiratory failure, renal failure, stroke, and mortality were similar in the two groups, although there were no mortalities in the CABG plus TMR group.
TMR as an adjunctive revascularization to CABG in selected patients with limited options may improve in-hospital outcomes.
Title: Transmyocardial laser revascularization combined with coronary artery bypass grafting: a multicenter, blinded, prospective, randomized, controlled trial.
Authors: Allen KB, Dowling RD, DelRossi AJ, Realyvasques F, Lefrak EA, Pfeffer TA, Fudge TL, Mostovych M, Schuch D, Szentpetery S, Shaar CJ.
Publication: J Thorac Cardiovasc Surg. 2000 Mar;119(3):540-9.
We sought to assess the safety and efficacy of transmyocardial revascularization combined with coronary artery bypass grafting in patients not amenable to complete revascularization by coronary bypass alone.
A total of 263 patients whose standard of care was coronary artery bypass grafting and who had one or more ischemic areas not amenable to bypass grafting were prospectively randomized to receive coronary bypass of suitable vessels plus transmyocardial revascularization to areas not graftable (n = 132) or coronary bypass alone with nongraftable areas left unrevascularized (n = 131). Group preoperative demographics and operative characteristics were similar.
The operative mortality rate after coronary bypass/transmyocardial revascularization was 1.5% (2/132) versus 7.6% (10/131) after coronary bypass alone (P =.02). Patients undergoing both coronary bypass and transmyocardial revascularization required less postoperative inotropic support (30% vs 55%, P =.0001) and had a trend toward fewer insertions of intra-aortic balloon pumps (4% vs 8%, P =.13) than did patients having coronary bypass alone. Multivariable predictors of operative mortality were coronary artery bypass alone (odds ratio, 5.3; 95% confidence interval, 1.1-25.7; P =.04) and increased age (odds ratio, 1.1; 95% confidence interval, 1. 0-1.2; P =.03). One-year Kaplan-Meier survival (95% vs 89%, P =.05) and freedom from major adverse cardiac events defined as death or myocardial infarction (92% vs 86%, P =.09) favored the combination of coronary bypass and transmyocardial revascularization. Baseline to 12-month improvement in angina and exercise treadmill scores was similar between groups.
In a prospective, randomized, multicenter trial, transmyocardial revascularization combined with coronary artery bypass grafting in patients not amenable to complete revascularization by coronary bypass alone was safe; however, angina relief and exercise treadmill improvement were indistinguishable between groups at 12 months of follow-up. Operative and 1-year survival benefits observed after adjunctive transmyocardial revascularization require confirmation by a larger validation study, which is ongoing.
Title: One-year outcome after combined coronary artery bypass grafting and transmyocardial laser revascularization for refractory angina pectoris.
Authors: Stamou SC, Boyce SW, Cooke RH, Carlos BD, Sweet LC, Corso PJ.
Publication: Am J Cardiol. 2002 Jun 15;89(12):1365-8.
Long-term outcomes after coronary artery bypass graft surgery (CABG) plus transmyocardial revascularization (TMR) are largely unknown. We report the results of 30-day and 3-, 6-, and 12-month clinical follow-up after CABG plus TMR in a consecutive series of patients with refractory angina pectoris and > or = 1 myocardial ischemic area not amenable to CABG. All patients who underwent CABG plus TMR (n = 169) (mean age 63 +/- 10 years, 70% men, 51% with previous CABG, 82% were deemed inoperable at other heart surgery centers due to small vessels or diffuse disease) between March 1996 and February 2000 were clinically followed and end points of interest (survival, stroke, acute myocardial infarction, and revascularization) and angina class were recorded at 30 days and 3, 6, and 12 months after CABG. At 1 year, actuarial survival and event-free survival were 85% and 81%, respectively. At the end of the first year after the procedure, 7 patients (4%) had angina class III/IV versus 152 patients (90%) at baseline (p <0.001). Predictors of major adverse cardiac events were advanced age (odds ratio [OR] 3.4, 95% confidence intervals [CI] 1.2 to 9.4, p = 0.01), prolonged intensive care unit stay (OR 3.3, CI 1.1 to 9.7, p <0.001), new-onset atrial fibrillation (OR 2.8, CI 1.1 to 7.0, p = 0.02), and in-hospital myocardial infarction (OR 1.5, CI 1.3 to 1.7, p <0.001). Thus, procedural success at 30 days and overall event-free and actuarial survival in a high-risk population setting shows that CABG plus TMR is a safe revascularization option for patients with intractable angina pectoris.
Title: Angina and Its Management.
Authors: Kloner RA, Chaitman B.
Publication: J Cardiovasc Pharmacol Ther. 2017 May;22(3):199-209.
Angina pectoris is defined as substernal chest pain, pressure, or discomfort that is typically exacerbated by exertion and/or emotional stress, lasts greater than 30 to 60 seconds, and is relieved by rest and nitroglycerin. There are approximately 10 million people in the United States who have angina, and there are over 500 000 cases diagnosed per year. Several studies now show that angina itself is a predictor of major adverse cardiac events. In addition, angina is a serious morbidity that impedes quality of life and should be treated. In the United States, pharmacologic therapy for angina includes β-blockers, nitrates, calcium channel blockers, and the late sodium current blocker ranolazine. In other countries, additional pharmacologic agents include trimetazidine, ivabradine, nicorandil, fasudil, and others. Revascularization is indicated in certain high-risk individuals and also has been shown to improve angina. However, even after revascularization, a substantial percentage of patients return with recurrent or continued angina, requiring newer and better therapies. Treatment for refractory angina not amenable to usual pharmacologic therapies or revascularization procedures, includes enhanced external counterpulsation, transmyocardial revascularization, and stem cell therapy. Angina continues to be a significant cause of morbidity. Therapy should be geared not only to treating the risk factors for atherosclerotic disease and improving survival but should also be aimed at eliminating or reducing the occurrence of angina and improving the ability of patients to be active.
Title: Video-assisted thoracoscopic surgery approach for transmyocardial laser revascularization..
Authors: Bashir MA1, Lyle BC1, Nasr AS1, Parekh K1.
Publication: Interact Cardiovasc Thorac Surg. 2017 Nov 1;25(5):848-849.
Transmyocardial laser revascularization is an established therapy for refractory coronary artery disease. However, utilization of the technology is not as widespread as expected. This is despite the fact that the efficacy of the technology has been established in multiple prospective randomized trials. Furthermore, only about 5% of transmyocardial laser revascularization cases annually are performed in a minimally invasive fashion. We report a case of a female patient treated in a minimally invasive thoracoscopic fashion.