Ann Thorac Surg 2000;69:1098-1103
© 2000 The Society of Thoracic Surgeons
ORIGINAL ARTICLES: CARDIOVASCULAR
Perioperative cardiac function and predictors for adverse events after transmyocardial laser treatment
Ole Tjomsland, MDa,
Lars Aaberge, MDb,
Sven M. Almdahl, MD, PhDa,
Morten Dragsund, MDa,
Per Moelstad, MD, PhDa,
Kjell Saatvedt, MD, PhDa,
Kenneth Nordstrand, MD, PhDa
a Feiring Heart Clinic, Feiring, The National Hospital, University of Oslo, Oslo, Norway
b Division of Heart and Lung Diseases, The National Hospital, University of Oslo, Oslo, Norway
Address reprint requests to Dr Tjomsland, Feiring Heart Clinic, 2093 Feiring, Norway
e-mail: mrisberg{at}ah.telia.no
 |
Abstract
|
|---|
Background. Previous studies have reported that mortality and morbidity after transmyocardial laser treatment (TML) mainly occur perioperatively. The present study was designed to evaluate left-ventricular function and identify risk factors for cardiac-related adverse events in this phase.
Methods. Forty-nine patients were studied. The inclusion criteria were angina pectoris Canadian Cardiovascular Society Angina Score (CCSAS) class III and IV refractory to medical therapy and untreatable by coronary artery bypass graft or percutaneous transluminal coronary angioplasty, age less than 75 years, left ventricular ejection fraction greater than or equal to 30%, and myocardial regions with reversible ischemia. Hemodynamic data and cardiac adverse events were registered. The follow-up time was 30 days.
Results. A transient decrease in mean cardiac index (CI) was observed, reaching its minimum immediately after end of the surgical procedure (1.8 ± 0.4, p < 0.01 vs baseline). Two patients (4%) died during the postoperative period (30 days). Seventeen patients (35%) experienced adverse cardiac-related events, where CCSAS class IV, unprotected left main stem stenosis, and diabetes mellitus were identified as risk factors in a multivariate analysis.
Conclusions. A transient impairment of left ventricular function was observed after TML. The morbidity and mortality after TML were almost exclusively cardiac-related, identifying CCSAS class IV, unprotected left main stem stenosis, and diabetes as risk factors.
|
Introduction
|
|---|
Transmyocardial laser treatment (TML) is currently evaluated as a treatment modality for patients with end-stage coronary artery disease unsuitable for conventional revascularization with percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). TML was based on the hypothesis that the laser-made channels could contribute to myocardial perfusion by conducting blood from the left ventricular cavity into the ischemic myocardium [1]. However, experimental [2] and clinical data [3] indicate that the laser-made channels are occluded by thrombus, and thereafter with fibrous tissue, and consequently do not perfuse ischemic regions of the myocardium, not even in the acute setting when the channels presumably still are patent [4–6]. Results from uncontrolled multicenter trials suggest that TML with carbon dioxide laser leads to a decrease in physician-assessed angina scores and improved exercise tolerance [7]. Randomized trials comparing TML with medical treatment have demonstrated improvement in functional class of angina pectoris and lower incidence of unstable angina in patients with angina inamenable to PTCA or CABG after TML [8, 9]. However, observations regarding the effect of TML on myocardial perfusion are conflicting [10, 11], and the mechanisms responsible for the angina-relieving effect remain unclear. It has been suggested that TML provides angina-relief through destruction of myocardial peripheral nerve-endings [12], and over longer periods improved perfusion through induction of angiogenesis and collateral recruitment [13].
In the first clinical TML studies, the early mortality (30 days) was found to be between 11% and 20% [10, 14], mostly cardiac-related, indicating perioperative compromised cardiac function. The incidence of myocardial infarction after TML has been reported to vary between 2% and 20% [10, 14]. Schofield and coworkers [9] reported an early mortality of 5% in a randomized prospective study. Their favorable results were explained by the fact that patients with left ventricular ejection fraction (LVEF) less than 30%, and those requiring intravenous therapy to control angina were excluded. Furthermore, 1 year follow-up showed that the mortality in the TML group occurred almost entirely in the early postoperative period. Knowledge of the cardiac function in the perioperative phase after TML is essential for optimizing the postoperative care. The aim of the present study was to evaluate perioperative cardiac function and to identify risk-factors for cardiac-related adverse events after TML.
|
Material and methods
|
|---|
Patient selection and demographics
From November 1995 through May 1998, 50 patients in "The Norwegian prospective randomized trial on transmyocardial revascularization versus optimal medical treatment in patients with refractory angina pectoris" were enrolled (Table 1). The protocol was approved by the regional board of ethics in medical research September 25, 1995. Informed consent was signed prior to inclusion. The inclusion criteria were angina pectoris CCSAS (Canadian Cardiovascular Society Angina Score) class III and IV refractory to medical therapy and untreatable by CABG or PTCA, age less than 75 years, LVEF estimated by multiple-gated acquisition (MUGA) ventriculography greater than or equal to 30%, and reversible ischemia assessed with 99Tc tetrofosmin single photon emission computed tomography (SPECT) and dobutamine stress-ecchocardiography. Exclusion criteria were intolerance to anesthesia, uncompensated heart failure, and severe chronic obstructive pulmonary disease. In 1 patient, as previously reported [15], LAD was judged intraoperatively to be graftable, revascularized with a LIMA graft after completion of the TML procedure, and consequently excluded from the present study. Demographics of the 49 patients included in the study are depicted in Table 1. The follow-up time was 30 days.
Anesthesia
The patients were premedicated with a peroral dose of diazepam or an intramuscular injection of morphine-chloride and scopolamine. Anesthesia was induced with a bolus dose of fentanyl and thiopental, and muscle relaxation was achieved by pancuroniumbromide. Intubation was performed with a single-lumen tube. Anesthesia was maintained with fentanyl and isofluran. Intravenous nitroglycerin was routinely administered postoperatively, and was continued for the next 20 hours. Postoperative pain control was obtained by thoracal epidural application of marcain and morphine the first 1 to 3 postoperative days. The patient’s preoperative medication was continued and adjusted as necessary during the postoperative period.
Operative technique
All the surgical procedures were performed by the same surgeon (K.N.). The patients were positioned in a 45 degree right lateral decubitus, and a left anteromedial thoracotomy was performed through the fourth or fifth intercostal space. The pericardium was identified, and then opened anteriorly longitudinally to the phrenic nerve. Present adhesions were divided to expose the surface of the left ventricle. Postoperative bleeding was drained through a chest tube, which was removed the first postoperative day.
Laser technique
A carbon dioxide laser (The Heart Laser; PLC, Milford, MA) was used to create transmyocardial channels, synchronized with the R wave of the electrocardiogram. The laser energy was delivered to the myocardium through a handpiece placed on the epicardial surface. The pulse duration was set to deliver 30 to 50 J at each firing. Penetration of the left ventricular cavity was confirmed by transesosphageal ecchocardiography. The density of the channels were approximately 1 to 2 pr cm2. Bleeding from the channels was controlled with digital pressure, or an epicardial suture if necessary.
Intraoperative and postoperative assessment of cardiac function
After induction of anesthesia, a 7.5 F gauge thermal lament-wrapped flow-directed pulmonary artery catheter (IntelliCath; Baxter Healthcare Corp, Irvine, CA) was introduced through the left subclavian vein using a 8.5 F introducer (Arrow Int, Reading, PA). This catheter was used to assess left ventricular function over the first 20 postoperative hours with a semicontinuous monitoring of cardiac output (CO), pulmonary artery blood pressure (PAP), and mixed venous oxygen saturation [16]. Cardiac index (CI) and stroke volume (SV) were calculated.
Data analysis
The data were registered, categorized into subgroups, and analyzed. The subgroups were patients recovering from the perioperative phase without adverse events (group nAE), and those who developed cardiac-related adverse events, defined as cardiac death, myocardial infarction, postoperative left ventricular failure requiring pharmacological support, or intraaortic balloon pump (IABP) (group AE).
Statistical analysis
Analysis of variance for repeated measurements (ANOVA) was used to evaluate the hemodynamic data within and between the two groups. Appearing differences were evaluated with a Tukeys posthoc test. A two sampled Student’s t-test, or a Fisher’s exact test, was used as appropriate, to evaluate the difference in demographics and the perioperative data between the groups. Data not normally distributed according to Skewness test, were evaluated with a Wilcoxon sign rank test. Multiple logistic regression analysis was used to predict risk factors for developing adverse events, employing a forward selection procedure, entering at each step the variable inducing the largest change in the log likelihood in the model. Data are presented as mean ± standard deviation (SD), and range is presented when appropriate. Differences were considered statistically significant when the p value was less than 0.05. Statistical analysis were performed with the NCSS program (Number Cruncher Statistical System, Kaysville UT), the multiple logistic regression analysis with the SYSTAT program (SPSS Inc, Chicago IL).
|
Results
|
|---|
Operative data
Mean operating time was 82 ± 23 minutes (55 to 175), no differences were found between group nAE and group AE (Table 2). An average of 48 ± 7 (30 to 62) laser channels were created in each heart, with no significant difference between the two groups. Arrhythmias requiring immediate treatment were not observed during the surgical procedure. Intraoperative deaths did not occur.
Hemodynamics
A significant increase in heart rate, compared to the baseline value, was observed 4 hours after operation, this level was maintained throughout the observation period (Table 3, Figs 1–6). Mean stroke volume was significantly increased 8 and 12 hours postoperatively. No significant alterations in mean systemic or pulmonary blood pressure was observed the first 20 hours after operation. After the end of the surgical procedure, a significant decrease in CI and mixed venous saturation was observed. Cardiac index reached baseline value 1 hour postoperatively, increasing to its maximal value 12 hours after operation, whereas mixed venous oxygen saturation remained significantly decreased throughout the observation period.
View larger version (14K):
[in this window]
[in a new window]
|
Fig 1. A significant increased heart rate was observed in group AE vs group nAE at 16 hours postoperatively.
|
|
View larger version (15K):
[in this window]
[in a new window]
|
Fig 2. A significant lower stroke volume was observed in group AE vs group nAE at 12, 16, and 20 hours postoperatively.
|
|
View larger version (12K):
[in this window]
[in a new window]
|
Fig 3. No significant differences in mean systemic arterial blood pressure were observed between group AE vs group nAE during the observation period.
|
|
View larger version (13K):
[in this window]
[in a new window]
|
Fig 4. No significant alterations in mean pulmonary artery blood pressure were observed between group AE vs group nAE during the observation period.
|
|
View larger version (15K):
[in this window]
[in a new window]
|
Fig 5. The differences appearing between the two groups in cardiac index (CI) did not reach the level of statistical significance, although CI increased significantly vs baseline after 3 hours in group nAE, whereas a significant increase in group AE first was observed after 8 hours.
|
|
View larger version (16K):
[in this window]
[in a new window]
|
Fig 6. A significant lower mixed venous oxygen saturation was observed 4, 16, and 20 hours postoperatively in group AE vs group nAE.
|
|
Cardiac complications
Four patients (8%) developed myocardial infarctions. This diagnosis was based upon infarct-specific changes in cardiac enzymes (CK-MB-isoenzyme values above 50 µg/L ASAT above 100 U/L and ASAT/ALAT ratio more than 2) and development of Q-waves in electrocardiogram. Two of the patients suffering myocardial infarction died in the postoperative phase (2 and 14 days postoperatively). Seventeen patients (35%) developed left ventricular failure. Two patients (4%) needed IABP. Seven patients (14%) developed postoperatively atrial fibrillation (1 to 3 days postoperatively), and in 2 patients (4%) ventricular arrhythmias, all converted pharmacologically.
Other complications
Four patients (8%) were treated for postoperative pneumonia, and 2 patients (4%) required reintubation. These patients arose exclusively from group AE. No patients had pneumothorax. Two patients required blood transfusions in the postoperative period. Renal failure was observed in 1 patient (2%), and 2 patients (4%) developed urinary tract infections. Superficial wound infection treated with antibiotics occurred in 2 patients (4%). In 1 patient (2%), the chest tube had to be removed surgically in general anesthesia the first postoperative day. None of the patients discharged alive had neurological deficits detectable by clinical examination.
Risk factors for developing cardiac adverse events
Univariate analysis (Table 1) identified preoperative CCSAS functional class IV, diabetes mellitus, unprotected left main stem stenosis without patent grafts, low left ventricular ejection fraction, preoperative use of heart failure medication (ACE-blockers and diuretics), and age, as factors disposing for cardiac related adverse events after TML. After adjustment with a model of multiple logistic regression preoperative CCSAS class IV, diabetes mellitus and unprotected left main stem stenosis were identified as risk factors for cardiac related adverse events.
|
Comment
|
|---|
The present study is the first to assess left ventricular function with a semicontinuous assessment of cardiac output in the perioperative phase (20 hours) after TML. Cardiac output decreased significantly immediately after end of the surgical procedure, reaching preoperative values after 1 hour. In the period between 4 and 20 hours after end of the surgical procedure there was a significant increase in cardiac output compared to the baseline value. Adverse events, defined as death, myocardial infarction, and low cardiac output requiring inotropic support or IABP, were observed in 17 patients (35%). In patients developing adverse events, heart rate was significantly increased, while stroke volume, cardiac output, and mixed venous oxygen saturation were significantly decreased during the first 20 hours. Preoperative CCSAS class IV, unprotected left main stem stenosis, and diabetes mellitus were identified as risk factors.
The pulmonary artery catheter used to monitor cardiac output, and mixed venous oxygen saturation was introduced after induction of general anesthesia, the preoperative value of cardiac output does not accordingly reflect the physiological baseline. The normal value of CI, after traditional cardiac operation is reported to be between 2.2 and 4.4 L/min/m2, a value below this level during the early postoperative period increases the probability of mortality and morbidity [17]. In the present study, mean CI was below this level the first 3 postoperative hours. A moderate decrease in heart rate and stroke volume was observed during the first postoperative hours, although it did not reach the level of statistical significance. Since the mean pulmonary and systemic arterial pressures, as indicators of preload and afterload were not significantly altered the first hours after operation, when the lowest level of cardiac output was observed, the significant decrease in cardiac output is probably caused by impaired myocardial contractility. The laser treatment per se and the manipulation of the heart during the surgical procedure could presumably cause transient myocardial dysfunction. Moreover, experimental models [2, 18] have demonstrated that TML performed with creation of 1 channel per cm2 leads to necrosis of approximately 6% of the myocardium subjected to TML. Microscopic examination of human myocardium 2 hours after TML showed that the myocardium surrounding the laser-made channels is characterized by myofibrillary degeneration and edema, potentially reversible injuries that could lead to a transient depressed myocardial function [19].
Lutter and colleagues [19] studied the left ventricular function the first 6 hours after TML, and found in contrast to our results, that CI did not decrease in patients with LVEF greater than 35%. However, patients with LVEF less than 35% experienced a significant transient reduction in CI after end of the surgical procedure, and concluded that IABP should be started preoperatively in patients with reduced left ventricular contractile reserve, in order to support the phase of reversible myocardial damage induced by TML. The patients in the group with LVEF less than 35% included in the study of Lutter and colleagues had unstable angina at the time of operation and were in addition to IABP treated intraoperatively and postoperatively with inotropic support with norepinephrine or epinephrine. Several other investigators have also studied the effects of TML in patients with unstable angina [20, 21], and reported an early mortality (30 days) of 16 and 20%. Patients with unstable angina are obviously high-risk patients, primarily in need of myocardial revascularization to prevent myocardial infarction, ischemia induced arrhythmias, and heart failure. Although the term, transmyocardial revascularization (TMR), has been used to describe the laser procedure, where multiple laser made transmyocardial channels are created in the left ventricular wall, results from various studies have failed to demonstrate increased myocardial perfusion after TML in a variety of animal models of acute myocardial ischemia [4, 6, 22]. Also, the results regarding the effect of TML on myocardial perfusion observed in clinical studies [10, 11] are conflicting. It has been shown that, TML protects against ventricular arrhythmias in experimental models of acute myocardial ischemia [6, 18], however the potential antiarrhythmic effect of TML has not been studied in patients with ischemic heart disease. In contrast to patients undergoing CABG, offering improved myocardial perfusion immediately after operation, patients treated with TML face the challenges of the postoperative phase without the potential of a surgically improved myocardial perfusion. As long as no effect on objective endpoints, such as survival, cardiac function, or perfusion, can be unequivocally demonstrated in prospective randomized clinical trials, TML should be recognized as symptomatic treatment. Thus, in order to minimize the morbidity and mortality after TML, precaution should be taken to avoid treatment of patients at risk of developing postoperative left ventricular dysfunction, including patients with unstable angina.
In conclusion, we found that the intraoperative and perioperative phases after TML are characterized by a transient impairment of left ventricular function, with a significant decrease of CI immediately after operation, reaching preoperative values after 1 hour. The morbidity and mortality after TML were almost exclusively cardiac-related. Preoperative CCSAS class IV, unprotected left main stem stenosis, and diabetes mellitus were identified as risk factors. Further research is needed to evaluate whether optimization of perioperative cardiac function and adjustment of the indications for TML can decrease the incidence of cardiac-related mortality and morbidity in patients with stable angina.
|
References
|
|---|
-
Mirhoseini M., Cayton M.M. Revascularization of the heart by laser. J Microsurg 1981;2:253-260.[Medline]
-
Fisher P.E., Khomoto T., DeRosa C.M., Spotnitz H.M., Smith C.R., Burkhoff D. Histologic analysis of transmyocardial channels. Ann Thorac Surg 1997;64:466-472.[Abstract/Free Full Text]
-
Schweitzer W., Schneider J., Maas D., Hardmeier T. Transmyocardial laser revascularization. Postmortal myocardial histomorphology of laser channels in 10 patients 1 to 18 days after treatment with a CO2-laser. Pathologe 1997;18:374-384.[Medline]
-
Kohmoto T., Fisher P.E., Gu A., et al. Does blood flow through Holmium. Ann Thorac Surg 1996;61:861-868.[Abstract/Free Full Text]
-
Hardy R.I., James F.W., Millard R.W., Kaplan S. Regional myocardial blood flow and cardiac mechanics in dog hearts with CO2 laser-induced intramyocardial revascularization. Basic Res Cardiol 1990;85:179-197.[Medline]
-
Lutter G., Yoshitake M., Takahashi N., et al. Transmyocardial laser-revascularization. Eur J Cardiothorac Surg 1998;13:694-701.[Abstract/Free Full Text]
-
Burns S.M., Sharples L.D., Tait S., Caine N., Wallwork J., Schofield P.M. The transmyocardial laser revascularization international registry report. Eur Heart J 1999;20:31-37.[Abstract/Free Full Text]
-
March R.J. Transmyocardial laser revascularization with the CO2 laser. Semin Thorac Cardiovasc Surg 1999;11:12-18.[Medline]
-
Schofield P.M., Sharples L.D., Caine N., et al. Transmyocardial laser revascularisation in patients with refractory angina. Lancet 1999;353:519-524.[Medline]
-
Cooley D.A., Frazier O.H., Kadipasaoglu K.A., et al. Transmyocardial laser revascularization. J Thorac Cardiovasc Surg 1996;111:791-797.[Abstract/Free Full Text]
-
Diegeler A., Schneider J., Lauer B., Mohr F.W., Kluge R. Transmyocardial laser revascularization using the Holium. Eur J Cardiothorac Surg 1998;13:392-397.[Abstract/Free Full Text]
-
Kwong K.F., Kanellopoulos G.K., Nickols J.C., et al. Transmyocardial laser treatment denervates canine myocardium. J Thorac Cardiovasc Surg 1997;114:883-889.[Abstract/Free Full Text]
-
Spanier T., Smith C.R., Burkhoff D. Angiogenesis. J Clin Laser Med Surg 1997;15:269-273.[Medline]
-
Nagele H., Kalmar P., Lubeck M., et al. Transmyocardial laser revascularization—a treatment option for coronary heart disease?. Z Kardiol 1997;86:171-178.[Medline]
-
Saatvedt K., Dragsund M., Nordstrand K. Transmyocardial laser revascularization and coronary bypass grafting without cadiopulmonary bypass. Ann Thorac Surg 1996;62:323-324.[Free Full Text]
-
Yelderman M.L., Ramsay M.A., Quinn M.D., Paulsen A.W., McKnown R.C., Gillmann P.H. Continuous thermodilution cardiac output measurements in intensive care unit patients. J Cardiothor Vasc Anes 1992;6:270-274.
-
Dietzman R.H., Ersek R.A., Lillehei C.W., Castañeda A.R., Lillehei R.C. Low output syndrome. Recognition and treatment. J Thorac Cardiovasc Surg 1969;57:138-150.[Medline]
-
Tjomsland O., Grund F., Kanellopoulos G.K., Kvernebo K., Ilebekk A. Transmyocardial laser induces coronary hyperemia and reduces ischemia-related arrhythmias, but fails to delay development of myocardial necrosis after coronary artery occlusion in pigs. J Cardiovasc Surg 1999;40:325-331.[Medline]
-
Lutter G., Saurbier B., Nitzsche E., et al. Transmyocardial laser revascularization (TMLR) in patients with unstable angina and low ejection fraction. Eur J Cardiothorac Surg 1998;13:21-26.[Abstract/Free Full Text]
-
Dowling R.D., Petracek M.R., Selinger S.L., Allen K.B. Transmyocardial revascularization in patients with refractory, unstable angina. Circulation 1999;98:73-76.[Abstract/Free Full Text]
-
Allen K.B., Dowling R.D., Heimansohn D.A., Reitsma E., Didelot L., Shaar C.J. Transmyocardial revascularization utilizing a Holmium. Eur J Cardiothorac Surg 1998;14(Suppl 1):100-104.
-
Whittaker P., Kloner R.A., Przyklenk K. Laser-mediated transmural myocardial channels do not salvage acutely ischemic myocardium. J Am Coll Cardiol 1993;22:302-309.[Abstract]
Accepted for publication September 16, 1999.
This article has been cited by other articles:
|
|
|
|
 
C. R. Bridges, K. A. Horvath, W. C. Nugent, D. M. Shahian, C. K. Haan, R. J. Shemin, K. B. Allen, and F. H. Edwards
The Society of Thoracic Surgeons practice guideline series: transmyocardial laser revascularization
Ann. Thorac. Surg.,
April 1, 2004;
77(4):
1494 - 1502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Guleserian, H. S. Maniar, C. J. Camillo, M. S. Bailey, R. J. Damiano Jr, and M. R. Moon
Quality of life and survival after transmyocardial laser revascularization with the holmium:YAG laser
Ann. Thorac. Surg.,
June 1, 2003;
75(6):
1842 - 1848.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Saririan and M. J. Eisenberg
Myocardial laser revascularization for the treatment of end-stage coronary artery disease
J. Am. Coll. Cardiol.,
January 15, 2003;
41(2):
173 - 183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Krabatsch, R. Petzina, H. Hausmann, A. Koster, and R. Hetzer
Factors influencing results and outcome after transmyocardial laser revascularization
Ann. Thorac. Surg.,
June 1, 2002;
73(6):
1888 - 1892.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Aaberge, K. Rootwelt, S. Blomhoff, K. Saatvedt, M. Abdelnoor, and K. Forfang
Continued symptomatic improvement three to five years after transmyocardial revascularization with co2 laser: A late clinical follow-up of the norwegian randomized trial with transmyocardial revascularization
J. Am. Coll. Cardiol.,
May 15, 2002;
39(10):
1588 - 1593.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
