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Keith B. Allen
Robert D. Dowling
Douglas R. Schuch
Thomas A. Pfeffer
Steven Marra
Edward A. Lefrak
Tommy L. Fudge
Mark Mostovych
Sibu P. Saha
Douglas Murphy
Hugh Dennis
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Right arrow Coronary disease

Ann Thorac Surg 2004;78:458-465
© 2004 The Society of Thoracic Surgeons

Original article: cardiovascular

Adjunctive transmyocardial revascularization: five-year follow-up of a prospective, randomized trial

Keith B. Allen, MDa*, Robert D. Dowling, MDb, Douglas R. Schuch, MDc, Thomas A. Pfeffer, MDd, Steven Marra, MDe, Edward A. Lefrak, MDf, Tommy L. Fudge, MDg, Mark Mostovych, MDh, Szabolc Szentpetery, MDi, Sibu P. Saha, MDj, Douglas Murphy, MDk, Hugh Dennis, MDl

a Departments of Cardiothoracic Surgery, St. Vincent Hospital, Indiana Heart Institute, Indianapolis, Indiana, USA
b University of Louisville, Jewish Heart and Lung Institute, Louisville, Kentucky, USA
c Sutter Memorial Hospital, Sacramento, California, USA
d Kaiser Permanente Medical Center, Los Angeles, California, USA
e Cooper Hospital, Camden, New Jersey, USA
f Fairfax Hospital, Falls Church, Virginia, USA
g Cardiovascular Institute of South-Surgery, Houma, Louisiana, USA
h St. Vincent Medical Center, Jacksonville, Florida, USA
i Sentara Norfolk General Hospital, Norfolk, Virginia, USA
j Central Baptist Hospital, Lexington, Kentucky, USA
k St. Joseph's Hospital, Atlanta, Georgia, USA
l North Ridge Hospital, Fort Lauderdale, Florida, USA

Accepted for publication April 12, 2004.

* Address reprint requests to Dr Allen, 10590 N Meridian St, Suite 105, Indianapolis, IN 46260, USA
e-mail: kallen2340{at}aol.com

Presented at the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 26–28, 2004.


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 
BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 
Due to the success in treating atherosclerotic heart disease with medical and percutaneous therapies, patients are increasingly being referred for coronary artery bypass grafting (CABG) later in their disease process after having developed a pattern of diffuse coronary artery disease. Incomplete revascularization due to diffusely diseased target vessels occurs in 10% to 25% of patients and is increasingly being recognized as an important predictor of perioperative adverse events [1, 2]. In particular, incomplete revascularization in the elderly has been cited as an independent predictor of operative mortality [1, 3, 4].

In five prospective, randomized trials at 1 year, sole therapy transmyocardial revascularization (TMR) provided patients with diffuse coronary artery disease not amenable to conventional surgical or percutaneous coronary intervention (PCI) superior angina relief, decreased rehospitalizations, and improved quality of life and event-free survival compared with continued medical therapy [5–9]. Three-year to 5-year follow-up of prospectively randomized trials demonstrated sustained angina relief following TMR with significantly superior angina relief compared to medical therapy [10–12]. In addition, 5-year follow-up of sicker class IV "no option" patients demonstrated significantly increased Kaplan-Meier survival in patients randomized to TMR [10]. Considering the success of sole therapy TMR in treating patients afflicted by diffuse coronary artery disease, TMR has been evaluated in conjunction with CABG in patients who would be incompletely revascularized by CABG alone in nonrandomized studies [13–15] and in three randomized trials [16–18]. In the largest trial involving 263 blinded patients, CABG/TMR provided operative and one-year survival benefits with similar angina relief (p = 0.2) compared with CABG alone [16]. We collected 5-year longitudinal follow-up of this single-blinded, prospective, multicenter, randomized controlled trial to evaluate the long-term benefits of CABG/TMR.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 Acknowledgments
 Discussion
 References
 
Patient selection and assessment
From 1996 to 1997, 263 patients whose standard of care was CABG but who had one or more viable target areas served by vessels that were not graftable due to diffuse disease were prospectively identified by angiography. Patients were randomized to receive either CABG alone or CABG of suitable vessels plus TMR (CardioGenesis Corporation, Foothill Ranch, CA) in areas not amenable to grafting. Study approval with one-year follow-up was obtained from the Institutional Review Board of each participating center and the Food and Drug Administration under an investigational device exemption. Details of enrollment and 1 year follow-up were previously reported [16].

All centers that participated in the original 1-year trial were encouraged to participate in this longitudinal follow-up. Thirteen centers whose research infrastructure allowed participation provided 218 patients for this report. This represented 83% (218/263) of the original study cohort with patients randomized to receive either CABG/TMR (n = 110) or CABG alone (n = 108). Approval for long-term follow-up was obtained in accordance with each center's Institutional Review Board and informed consent was obtained from patients. Baseline demographic and clinical characteristics of the two treatment groups were similar (Table 1). We evaluated long-term Canadian Cardiovascular Society (CCS) angina class, survival, and need for repeat revascularization. Long-term exercise treadmill scores were not collected as 1-year results were limited and showed no difference between groups.


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  		Table 1. Patient Demographics

 
Operative procedure
The CABG procedure and postoperative care were center-specific and comparable between groups at each center. Patients randomized to CABG alone had viable target areas that were served by vessels unsuitable for grafting left untreated, whereas patients randomized to CABG/TMR had a mean of 25 ± 10 channels placed in viable areas unable to be grafted, with individual channels spaced approximately 1 cm apart. The technique of adjunctive TMR using a holmium:yttrium-aluminum-garnet (holmium:YAG) laser has been described previously [16, 19]. The operative characteristics of both groups were similar with respect to time on bypass and number and distribution of bypassed vessels (Table 2).


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  		Table 2. Operative Characteristics

 
Follow-up
Patients were blinded to treatment assignment through 1-year follow-up. Follow-up was obtained through telephone interviews and self-administered worksheets and was complemented with hospital and physician medical records. Mortality follow-up was 100% and included querying of the Social Security Death Index. CCS angina class assessment was determined by blinded evaluators independent of study investigators and was obtained in 89% (128/144 [68 CABG/TMR; 60 CABG alone]) of survivors who completed the original trial. Mean follow-up was 5.0 ± 1.7 years (range: 4.3 to 6.7 years).

Statistical analysis
Demographic and baseline variables were analyzed using a two-sample t test for continuous variables and Fischer's exact test, or the Cochran-Mantel-Haenszel test for qualitative variables. As defined in the original study protocol, mean CCS angina class distribution for each group at baseline and follow-up was analyzed using the Cochran-Mantel-Haenszel test. A covariate analysis of long-term CCS angina class was performed by multilinear regression, treating the final CCS class as a continuous variable. An additional subanalysis was conducted using Fischer's exact test to determine the difference between groups regarding the proportions of patients who were either angina free or free from recurrent severe (class III/IV) angina. Comparison of operative mortality rates between groups was determined using Fischer's exact test. Kaplan-Meier survival estimates were used to analyze survival through the current follow-up; groups were compared using the Wilcoxon-Gehan test. Patients at risk are those at the exact time point. Long-term covariate analyses of freedom from angina and of mortality were performed using Cox proportional hazards regression considering baseline variables (age, gender, ejection fraction, history of diabetes, hypercholesterolemia, and hypertension, prior myocardial infarction, prior CABG, and prior PCI), treatment arm, and number and type of vessels bypassed. Variable selection was by backward elimination, where the criterion for removal from the model was a Wald X-square p value more than 0.2. All statistical analyses were performed using SAS software version 8.2 (SAS Institute, Inc., Cary, NC).


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Comment
 Acknowledgments
 Discussion
 References
 
Effectiveness
Baseline CCS angina class distribution was similar between groups (2.9 ± 1.3, CABG/TMR; 2.8 ± 1.3, CABG alone, p = 0.50). Whereas groups experienced significant improvement in CCS angina class from baseline during follow-up (Figs 1 and 2), CABG/TMR patients enjoyed a significantly lower mean angina score at 5 years compared with CABG alone patients (0.4 ± 0.7 vs 0.7 ± 1.1, p = 0.05). Significant predictors of final CCS angina class included randomization to CABG/TMR (p = 0.02) and no prior vascular surgery (p = 0.003). Subanalyses revealed that significantly fewer CABG/TMR compared with CABG alone patients had severe angina (class III/IV) at 5 years (0% [0/68] vs 10% [6/60], p = 0.009), although groups were well matched in this regard at baseline (68%, CABG/TMR vs 74%, CABG alone, p = 0.37). In addition, there tended to be more CABG/TMR compared with CABG alone patients who were angina free (78% [53/68] vs 63% [38/60], p = 0.08).



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  		Fig 1. Mean CCS angina class through 5 years. {square} = patients randomized to adjunctive transmyocardial revascularization and coronary artery bypass grafting; {diamondsuit} = patients randomized to coronary artery bypass grafting alone. (CCS = Canadian Cardiovascular Society.)

 


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  		Fig 2. Canadian Cardiovascular Society angina class distribution at baseline and long term. {square} = class I or none; = class II; {blacksquare} = class III or IV. (CABG/TMR = patients randomized to adjunctive transmyocardial revascularization and coronary artery bypass grafting; CABG alone = patients randomized to coronary artery bypass grafting alone.)

 
Significantly more diabetic patients who received CABG/TMR were free from angina at 5 years compared with diabetics who received CABG alone (93% [26/28] vs 63% [12/19], p = 0.02). In a multivariable analysis, predictors of long-term freedom from angina included diabetes (p = 0.04), no prior CABG (p = 0.002) and a trend favoring CABG/TMR treatment (p = 0.06, Table 3). There were no significant differences between groups in overall usage of ß-adrenergic blockers, antianginals, diuretics, or angiotensin-converting enzyme inhibitors at follow-up. Due to the advancements that have occurred in medications since the original trial (eg, new combination drugs, brands and alternate dosage forms) a detailed dose-related analysis of medication usage was not appropriate.


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  		Table 3. Multivariable Regression Analysis of Predictors of Long-Term Freedom From Angina

 
During follow-up, no additional CABG procedures were performed although a similar incidence of PCI occurred in each group (13% [14/110], CABG/TMR vs 11% [12/108], CABG alone, p = 0.84). In a multivariable model that considered the effect of postrandomization PCI on long-term angina improvement, the statistically significant superiority of CABG/TMR versus CABG alone was maintained, both in terms of long-term improvement (p = 0.04) and, in this analysis, freedom from angina (p = 0.04). After excluding patients who received a postrandomization PCI procedure, long-term CCS angina improvement remained superior following CABG/TMR compared to CABG alone (0.3 ± 0.7 vs 0.6 ± 1.1, p = 0.05). Similarly, exclusion of patients who received PCI during follow-up continued to demonstrate that significantly fewer CABG/TMR patients suffered from severe class III/IV angina (0% [0/53] vs 10% [5/48], p = 0.02).

Survival
A strong trend toward reduced operative mortality (in-hospital and ≤ 30 days) was observed after CABG/TMR compared with CABG alone (0.9% [1/110] vs 5.6% [6/108], p = 0.06), with deaths randomly distributed among centers. Kaplan-Meier survival was comparable between groups at 6 years (76%, CABG/TMR vs 80%, CABG alone, p = 0.90, Fig 3). Baseline demographic variables and clinical factors, along with the treatment group assignment, were included in a multivariable model to determine covariate predictors of long-term survival (Table 4). The presence of diabetes, prior dialysis, decreased ejection fraction and increased age were found to be predictive of increased long-term mortality risk.



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  		Fig 3. Kaplan-Meier survival estimates. (CABG/TMR = patients randomized to adjunctive transmyocardial revascularization and coronary artery bypass grafting; CABG alone = patients randomized to coronary artery bypass grafting alone.)

 

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  		Table 4. Multivariable Regression Analysis of Predictors of Long-Term Mortality

 

   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
Acknowledgments
 Discussion
 References
 
Randomized, multicenter clinical trials have shown that sole therapy TMR provides superior angina relief, improved exercise times, and improved quality-of-life/event-free survival compared with continued medical management at 1 year [5–9]. Blinded 5-year follow-up of randomized severe class IV angina patients demonstrated that holmium:YAG TMR not only provided a sustained and significant angina improvement compared to patients randomized to medical therapy (p < 0.001) but also conferred a survival advantage over medical therapy alone (65% vs 52%, p = 0.05) with a significantly reduced risk of late death beyond 1 year (p = 0.03) [10]. In the only other long-term follow-up of a randomized sole therapy TMR trial involving primarily class III angina patients, Aaberge and colleagues [11] reported significant angina relief 3 to 5 years after TMR using a carbon dioxide laser compared to medical therapy, however, no survival advantage was observed. This persistent improvement in angina is supported by a long-term follow-up of a series of 78 patients who received carbon dioxide TMR [12]. Although 5-year survival following carbon dioxide TMR in this series was only 49%, surviving patients enjoyed improved quality of life and a significant reduction in angina from baseline. Based on results replicated in multiple clinical trials, TMR is recommended by the American College of Cardiology/American Heart Association (ACC/AHA) and the Society of Thoracic Surgeons (STS) for the treatment for medically refractory, chronic stable angina in patients who are not candidates for PCI or CABG [20, 21].

Unlike the clear benefit observed following sole therapy TMR, the incremental benefit of TMR combined with CABG in patients who would be incompletely revascularized by CABG alone has been somewhat more difficult to assess due to the influence of adjacent bypass grafts and the lack of randomized control arms in some studies [13–15]. To date, three randomized controlled trials have evaluated CABG/TMR, thus permitting a more rigorous determination of its relative safety and effectiveness in a defined patient population [16–18]. In the largest trial involving 263 patients, patients randomized to CABG/TMR had a reduced operative mortality (1.5% vs 7.6%, p = 0.02), although the Parsonnet-predicted mortality risk was comparable (6.3%, CABG/TMR vs 6.6%, CABG alone, p = 0.80). CABG/TMR patients also had improved 1-year Kaplan-Meier survival (95% vs 89%, p = 0.05) and similar angina relief at 1 year (p = 0.2) compared with patients who received CABG alone [16].

Our long-term follow-up of these prospectively randomized patients reveals a significantly lower mean CCS angina class in CABG/TMR patients with similar long-term survival between groups. Of particular clinical importance is the significantly lower incidence of developing recurrent severe class III or IV angina following CABG/TMR, and the trend toward more CABG/TMR patients who are angina free as determined by blinded assessors at 5-year follow-up. Whereas subsequent percutaneous interventions occurred during follow-up, no patients required repeat CABG and a similar number of angioplasties were performed in each group. Even after excluding patients with subsequent interventions the angina relief afforded CABG/TMR patients remained significant.

In a second randomized study involving 49 patients considered at high risk for CABG, Frazier and colleagues [17] reported a trend toward lower operative mortality (9% vs 33%, p = 0.09) in patients randomized to CABG/TMR. In the smallest of the three randomized trials, a small single center study of 20 patients [18], significant angina class improvement from baseline was observed in both groups through 36 months, with superior exercise times observed through 18 months in CABG/TMR patients. Although exercise times were indistinguishable between groups at 36 months these results may be equivocal due to study design.

The early survival benefit reported by two of these randomized trials involving patients with diffuse coronary artery disease who would be incompletely revascularized by CABG alone has been criticized. In a recent retrospective, nonrandomized registry study, Peterson and colleagues [22] reported similar operative mortality and morbidity following CABG/TMR compared to a concocted case matched control group. The control group was derived by querying the STS database for patients with three-vessel disease who had CABG alone but who received less than three grafts, with the assumption that these patients were similar to patients who received CABG/TMR. The appropriateness of this comparison is questionable because it assumes that incomplete revascularization in the control group occurred in an area of ischemic viable myocardium supplied by a diffusely diseased, ungraftable coronary artery and that all participating centers accurately and consistently defined three-vessel disease. Furthermore, the presence of diffuse coronary artery disease is increasingly being recognized as an independent risk factor for operative mortality, yet this important demographic is unfortunately not factored into commonly used models for predicting surgical risk, including the current STS adult cardiac database (Fig 4). Graham and coworkers [3] concluded that diffuse coronary artery disease, when appropriately quantified, is a powerful independent predictor of operative mortality. Similarly, Osswald and associates [1] determined that incomplete revascularization due to small or diffusely diseased targets, particularly in the elderly, increased operative risk and was a significant predictor of operative mortality following CABG. In one series, the presence of diseased but nongrafted arteries posed a significant negative influence on event-free survival defined as the absence of death, recurrent angina, myocardial infarction, and the need for repeat CABG [4]. Others concur with these findings, and further find that incomplete revascularization due to small or diffusely diseased vessels also significantly increases the risk of late cardiac events [23–25]. Thus, such case-matched comparisons against CABG/TMR-treated patients with diffuse coronary artery disease can be unreliable because control database sources fail to account for diffuse coronary artery disease and therefore underestimate predicted operative mortality and morbidity in this patient group [26].



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  		Fig 4. Two angiograms from demographically similar patients, both with Society of Thoracic Surgeons predicted operative mortality of 3.1%. The striking difference in the quality of coronary targets is not accounted for ([top] patient A: good quality, easily visualized; [bottom] patient B: poor quality due to diffuse disease), however, when calculating perioperative morbidity or mortality risk making case matched retrospective comparisons unreliable in patients with diffuse coronary artery disease.

 
This study has several limitations. First, randomization occurred preoperatively, and although patients were blinded to treatment assignment, surgeons could not be blinded to treatment group. The surgeon's belief in TMR could potentially influence surgical conduct and bias intraoperative decisions. Although the operative characteristics were similar between groups, nonsignificant increases in grafting of the circumflex artery and overall number of grafts placed per patient were found in the CABG alone group. Despite this, CABG alone patients still had worse overall angina compared to CABG/TMR patients. Secondly, this study is a longitudinal long-term follow-up of a prospectively conducted 1-year trial. This study was limited to assessments that could be made in a high proportion of patients with a high degree of confidence: blinded angina assessment independent of study investigators and survival. In addition, not all centers who enrolled patients in the original trial participated in this long-term follow-up study. Nonetheless, 83% (218/263) of the original study cohort was evaluable, with baseline demographics well matched between groups and which reflected the baseline demographics of the original study population.

Cardiac surgeons are increasingly faced with a more complex patient population who have developed a pattern of diffuse coronary artery disease and who have exhausted their nonsurgical options. Both randomized and nonrandomized trials have validated the safety of TMR combined with CABG. This 5-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.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
Discussion
 References
 
We thank William N. Anderson, PhD for statistical analysis of the data and CardioGenesis Corporation for reimbursement of study expenses.


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 Discussion
References
 
DR Valluvan M. JEEVANANDAM (Chicago, IL): We were involved with the PLC randomization group, and I know one of the problems with their randomization was there was a significant number of crossover patients. So I want to know with your technology, I take it this is the Cardiogenesis study, whether there was any crossover of patients, or was this strictly randomized and adhered to?

DR ALLEN: Are you talking about sole therapy?

DR JEEVANANDAM: Yes, sole therapy. And the other question I have is that you have shown angina relief. Do you have any scans to show improved perfusion in the patients who have had coronary artery bypass grafting (CABG) versus CABG/transmyocardial revascularization (TMR)?

DR ALLEN: Transmyocardial revascularization in this study was performed using a holmium:YAG laser manufactured by Cardiogenesis Corporation. Like the sole therapy TMR study that was reported by Dr. Frazier, we also allowed crossover from the medical to the surgical arm of the trial if they met a predefined treatment failure criteria. The crossover rate in the Frazier PLC study was 59%. It was 32% in our study.

Obviously the focus of this talk was not on discussing sole therapy patients but rather on our long term follow-up of a randomized CABG/TMR trial. However, 5-year follow-up of our randomized sole therapy TMR trial, which will be published shortly in the Annals along with the STS guidelines for TMR, demonstrates that whether you analyze the data on an intent-to-treat basis or as three separate groups, the angina relief was markedly positive for patients who got sole therapy TMR.

DR JEEVANANDAM: You reported on angina. Do you have any perfusion scans on these patients?

DR ALLEN: Evaluating perfusion studies following TMR has been mixed. Of the five sole therapy TMR randomized trials, two with holmium: YAG, three with CO2, only the Frazier CO2 study reported an improvement in perfusion. That study, however, has been criticized because it bases its conclusions on only 13 baseline to 12-month paired scans in the medical arm of the study. Furthermore, when the FDA audited that data, there was no clinical correlation between improvement in perfusion and improvement on thallium scans. Positron emission tomography (PET) scans may be a more sensitive test for perfusion and I am looking forward to seeing data on this topic from Emory University in the near future. We did not, however, perform thallium studies in this CABG/TMR trial.

DR JEEVANANDAM: One of the biggest criticisms we get from our cardiology colleagues is that, angina is better, but do you have better perfusion? If you have some kind of perfusion study on these patients, it would be more compelling.

DR ALLEN: I think looking for an improvement in perfusion makes the assumption that the mechanism is only angiogenesis. You could simply have a restructuring of the microcirculation because of the laser channel without an overall improvement in perfusion and still get angina relief. Failure to understand the mechanism behind TMR is why long term follow-up of randomized TMR trials is so important.

DR JEFFREY SELL (Baltimore, MD): I have a question. A lot of the patients we see that are incompletely revascularizable have diabetes, and therefore often have faulty warning systems or no angina at all. What is the role for TMR in that kind of a patient?

DR ALLEN: That is a very good question. In the original sole therapy trials, you had to have angina to be enrolled. The incidence of diabetes in this CABG/TMR study was about 40%. Angina relief in diabetic patients was similar to those that got CABG/TMR versus CABG alone.

DR ALICE M. MASCETTE (Bethesda, MD): What evaluation was done of concomitant medical therapy as a confounding variable in your postoperative patients?

DR ALLEN: That is a very excellent question, and I think the answer is these were center-specific decisions and not dictated by the protocol. However, when we reviewed medication usages, for example, statin use particularly, there was no difference between groups. Patients were discharged on similar amounts of ß blockers; aspirin was used universally on everybody. So we tried to follow in both groups AHA and ACC guidelines.

DR KEITH HORVATH (Chicago, IL): Thank you, Keith, for a nice presentation. I think this is important information, particularly in light of that recent Journal of the American College of Cardiology article. As you pointed out, and I think it is important for everyone to understand, these are CABG plus TMR patients. The data from the database that was used for that JACC article I think unfortunately has led to a concern that the adjunctive use of this device is inappropriate. I think that is completely false and I think you have helped show that that is the case.

But as a point of clarification, in answer to the questions that came up regarding sole therapy TMR, the perfusion scans for both of the randomized control trials with sole therapy CO2 TMR showed an improvement in perfusion. The Frazier study that you referred to had an 80% follow-up, and that, for the record, is necessary to be stated.

DR ALLEN: My response to that is I encourage you to read the PLC article in the New England Journal of Medicine, and I will stand by my earlier statement.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 

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