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Transmyocardial laser revascularization (TMLR) in patients with unstable angina and low ejection fraction
Abstract
Does perioperative use of the intraaortic balloon pump (IABP) improve the postsurgical outcome of patients presenting with endstage coronary artery disease, unstable angina and low ejection fraction transferred for transmyocardial laser revascularization (TMLR)?
TMLR, as sole therapy combined with the perioperative use of an intraaortic balloon pump has been assessed in seven patients with endstage coronary artery disease, unstable angina and low ejection fraction (EF < 35%). Six out of seven patients had signs of congestive heart failure. These patients are compared with 23 patients with endstage coronary artery disease, stable angina and EF > 35%, who were treated with TMLR as sole therapy without the use of IABP. The creation of transmural channels was performed by a CO2-laser. All patients were evaluated by hybrid positron emission tomography (perfusion SPECT and viability PET) and ventriculography preoperatively. Echocardiography, clinical status and hemodynamic assessment by Swan Ganz catheter were performed perioperatively.
The perioperative mortality of this combined procedure (TMLR and IABP) was zero. Three out of seven patients had pneumonia with complete recovery. Swan Ganz catheter examinations showed deterioration of LV-function after TMLR intraoperatively and improvement after 2 h and further after 6 h on ICU (P < 0.05). In contrast, a decrease of LV-function in sole TMLR patients with an EF > 35%) has not been observed. Patients with EF < 35% needed the IABP for 2.3 days and moderate dose catecholamines for a mean of 3.0 days. The postoperative EF and resting wall motion score index (WMSI) of all analysed LV segments (evaluated by echocardiography) did not change compared to baseline (EF 31.3+/-2.6 preop. to 32.8+/-3.2 postop.; WMSI: 1.75+/-0.14 at baseline to 1.71+/-0.17 postop.). The average Canadian Angina Class at the time of discharge decreased from 4.0+/-0 (baseline) to 2.3+/-0.5 (P < 0.05) and the NYHA-Index from 3.9+/-0.3 to 2.7+/-0.5. No patient had signs of angina pectoris, whereas two patients still had signs of congestive heart failure.
The reported data support our concept to start IABP preoperatively in patients with reduced LV contractile reserve in order to provide cardiac support during the postoperative phase of reversible decline of LV-function induced by TMLR.
... Other centers report similar results excepting a significant improvement in regional perfusion and metabolism [3,11]. The exact mechanism which facilitates these subjective and objective transmyocardial laser revascularization-related improvements remains as yet unknown [12,13]. Various acute animal models have provided contradictory results that have led investigators to differing conclusions as to patency, perfusion and global function after transmyocardial laser revascularization [2]. ...
... We drilled one and two CO 2 laser channels per em" in laser groups 1 and 2, repectively, because the number of channels that should be drilled is still a controversial topic [5,6]. Regarding the parameters of IMP, arrhythmia, perfusion, regional contractility, myocardial water content, and histochemistry we did not observe any difference between laser group 1 and 2. In contrast, laser group 1 indicated higher LVSWIm ax values at the end of the study compared to, laser group 2. One channel per em" is the most WIdely used channel density in clinical and experimental studies [2][3][4][5][7][8][9][10][11][12]; however, a general threshold of channel density should be defined for clinically treating myocardial ischemia, because carbon dioxide las~r channels significantly decrease global heart function shortly after transmyocardial laser :evascularizatio~in ischemic human [5,12] and even In healthy porcine myocardium [6]. ...
... We drilled one and two CO 2 laser channels per em" in laser groups 1 and 2, repectively, because the number of channels that should be drilled is still a controversial topic [5,6]. Regarding the parameters of IMP, arrhythmia, perfusion, regional contractility, myocardial water content, and histochemistry we did not observe any difference between laser group 1 and 2. In contrast, laser group 1 indicated higher LVSWIm ax values at the end of the study compared to, laser group 2. One channel per em" is the most WIdely used channel density in clinical and experimental studies [2][3][4][5][7][8][9][10][11][12]; however, a general threshold of channel density should be defined for clinically treating myocardial ischemia, because carbon dioxide las~r channels significantly decrease global heart function shortly after transmyocardial laser :evascularizatio~in ischemic human [5,12] and even In healthy porcine myocardium [6]. ...
Objective
The purpose of this study was to determine the effect of transmyocardial laser revascularization (TMLR) on myocardial perfusion and function in chronically ischemic myocardium.
Methods
In the first operation a stenosis of the left anterior descending artery was created in 20 open-chest anesthetized pigs to implement this ischemic model. In contrast, four pigs served as controls (thoracotomy only). Seven days later (2nd operation), all animals were studied at baseline by analyzing different parameters of perfusion (radioactive microspheres), function, and intramyocardial pressure. Afterwards, pigs who received a left anterior descending artery stenosis were randomized into one of three groups: animals in laser group 1 (n = 7) received one and in laser group 2 (n = 7) two laser channels per cm² in the left anterior descending artery territory. Animals of the ischemic group (n = 6) underwent the same procedures without transmyocardial laser revascularization. Three months later, the animals were re-studied (3rd operation) and additional analysis of histochemistry and myocardial water content was performed.
Results
Regional myocardial blood flow (RMBF) in laser group 2 revealed statistically higher RMBF values compared to the ischemic group (0.39±0.13 versus 0.14±0.12 ml/min/g; P = 0.043), after 3 months, whereas the absolute RMBF had not increased compared to the 1-week baseline values. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared to the initial values in all study groups (P = ns). Nevertheless, laser group 1 demonstrated relatively higher LVSWImax values compared to the ischemic (1.33±0.19 versus 0.93±0.16 mJ/kg; P = 0.03) and laser group 2 (1.33±0.19 versus 1.02±0.15; P = 0.024). Regional contractility of laser groups 1 and 2 recovered after 3 months (which had deteriorated shortly after transmyocardial laser revascularization) and increased under stress (100% versus 144.33±46.42, P = 0.029 and 100% versus 116.26±21.06, P = 0.034; respectively). In contrast, the corresponding ischemic group values were not different from intial values (P = ns).
Conclusions
This model of chronic regional ischemia demonstrates that CO2-laser revascularization significantly improves microperfusion and regional function, whereas the overall perfusion and global LV function is unchanged.
... The maximal LVSWI at baseline and end of study are summarized inFig. 1 for all groups. After 6 h maximal LVSWI in the ischemia and laser group 1 and 2 were reduced significantly [13] as compared to their preoperative value (36 vs. 38 and 41%; P 0.05) and to the 6 h value of the control group (P 0.01). At the end of the study maximal LVSWI in the ischemia-, laser 1-and laser 2 group did not show any difference. ...
... The maximal left ventricular stroke work index in the ischemia-, laser 1-and laser 2 group did not show any difference at the end of the experiment. All groups showed in average a mean reduction of 39% of their baseline value [13] . It might be speculated that the similarity in measurements of global left ventricular function after a 6 h observation period between the three ischemic groups was due to a too short time period (half an hour) between creating CO 2 channels and setting of the infarction. ...
This experimental study in pigs was undertaken to answer the question whether TMLR after acute myocardial infarction may improve regional myocardial perfusion, left ventricular function and diminish myocardial necrosis in the area at risk.
Thirty open-chest anesthetized pigs were observed for 6 h, six pigs served as controls. In 24 pigs, occlusion of the left anterior descending artery (LAD) beyond the first diagonal branch was performed: seven pigs had LAD occlusion only (ischemia group), and 17 pigs were treated by TMLR (using a CO2-laser, energy: 40 J) prior to coronary occlusion; nine pigs received one laser channel (1 mm diameter) per cm2 (laser group 1) and eight pigs two channels per cm2 in the LAD territory (laser group 2). Regional myocardial blood flow by microspheres, function (franc starling curves), histochemical assessment (triphenyl tetrazolium chloride, TTC and histology), were performed.
The lased pigs were less prone to ventricular fibrillation (laser group 2, 38%; laser group 1, 56%; ischemic group, 100%; P < 0.05), and showed a significant smaller area of necrosis (TTC) in the area at risk (laser group 1, 23%; laser group 2, 14%; vs. ischemia group, 31%; P < 0.01). There was no significant difference between laser-treated and ischemia hearts regarding the amount of blood flow into the infarcted LAD region and the maximal left ventricular stroke work index after 6 h (P = n.s). Regional myocardial blood flow: ischemia group, 4 +/- 5 ml/100 g/min; laser group 1, 3 +/- 10 ml/100 g/min, and laser group 2, 2 +/- 10 ml/100 g/min; maximal left ventricular stroke work index: ischemia group, 1.8 mJ/g; laser group 1, 2.1 mJ/g and laser group 2, 2.1 mJ/g.
This model of acute regional ischemia demonstrates that CO2-laser revascularization diminish significantly the incidence of ventricular fibrillation and necrosis in the area at risk, and does not change regional myocardial perfusion and global left ventricular function. This experiment indicates that TMLR may be an alternative in treating advanced ischemic heart disease.
... Moreover, experimental models [2,18] have demonstrated that TML performed with creation of 1 channel per cm 2 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 Fig 6. A significant lower mixed venous oxygen saturation was observed 4, 16, and 20 hours postoperatively in group AE vs group nAE. ...
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.
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.
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.
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.
... Other centers report similar results excepting a signi®cant improvement in regional perfusion and metabolism [6,7]. The exact mechanism which facilitates these subjective and objective TMLR-related improvements remains as yet unknown [8,9]. Therefore, this study was initialized to evaluate the long-term effectiveness of TMLR in the setting of chronic ischemia in porcine hearts. ...
... All of the above-mentioned study groups used the same CO 2 laser regimen to perform the TMLR operation, but it remains unclear why the long-term results of these studies determined by the objective parameter of perfusion are very different. Despite its increasing surgical use, careful stepby-step experimental and clinical validation of TMLR is required to prove its effectiveness in treating regional myocardial ischemia [1±3, 8,9]. ...
The long-term effectiveness of transmyocardial laser revascularization (TMLR) was evaluated in the setting of a severe left anterior descending artery (LAD) stenosis.
To employ the chronic ischemic model, pigs underwent three operative procedures over a 13-week period. In the first operation, an operative stenosis of the LAD was created. One week later, the animals were studied at baseline by analyzing different parameters of perfusion (microspheres), function and ECG changes. Afterwards, pigs were randomized into one of three different experimental groups: animals in laser group 1 received one laser channel (n=9) and laser group 2 two channels per cm(2) (n=6) in the LAD territory (using a CO(2)-laser). Animals of the ischemic group (n=12) underwent the same procedures without TMLR-treatment. Twelve weeks later, the animals were re-studied (third operation) and killed. Additional analysis of myocardial water content and histochemistry was performed.
Chronic myocardial ischemia and regional myocardial blood flow (RMBF) in laser group 2 revealed relatively higher RMBF values compared with the ischemic group (P=0.015), after 3 months, but no absolute improvement of perfusion at rest compared with baseline was observed in all experimental groups. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared with initial values in all study groups (P not significant). However, laser group 1 demonstrated relatively higher LVSWI(max) values in comparison with the ischemic group (P=0.013) as did laser group 2 (P=0.017). Regional contractility of the laser groups recovered after 3 months (which was deteriorated shortly after TMLR, P<0.001) and increased under stress compared with baseline (laser 1: P=0.015, laser 2: P=0.017). In contrast, the ischemic group did not show any difference from initial values (P not significant). The lased pigs of group 2 were less prone to intractable ventricular fibrillation (P=0.036 vs. ischemic group), and showed a significant smaller area of necrosis in the area at risk (P=0.012 vs. ischemic group).
This model of chronic regional ischemia demonstrates that CO(2)-laser revascularization significantly ameliorates microperfusion and regional contractility, and diminishes the incidence of ventricular fibrillation and necrosis in the area at risk. However, it does not change the overall perfusion and global LV function.
... The main risk factor was heart failure: in several studies, the mean LVEF was less than 30%. The authors also identified unstable angina, mitral regurgitation, and the absence of at least one coronary artery with preserved blood flow as risk factors [18][19][20][21][22]. ...
To evaluate the long-term results of TMLR using a CO 2 laser in combination with intramyocardial injection of ABMSC as an isolated procedure in patients with the end-stage coronary artery disease, the study included 20 patients (90% male), with a mean age of 58.4 ± 8.7 years. To assess the long-term results, patients were examined in a hospital. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Angina Questionnaire (SAQ) were used. The evolution of laboratory and instrumental indices, as well as medical therapy, was assessed. The end points of the study were death, acute myocardial infarction (AMI), repeated myocardial revascularization, recurrent hospitalizations due to coronary artery disease, and stroke. The changes in angina functional class were also evaluated. The median of follow-up period was 54 (36; 83) months, that is, 4.5 years. The analysis of the evolution of echocar-diographic data showed the absence of statistically significant changes in the following parameters: left ventricular end-diastolic diameter (EDD) (p = 0.967), end-systolic diameter (ESD) (p = 0.204), end-diastolic volume (EDV) (p = 0.852), end-systolic volume (ESV) (p = 0.125), and left ventricular ejection fraction (LVEF) (p = 0.120). The patients continued to regularly take the main groups of medications. Nitrate consumption was significantly reduced (p < 0.001). Significant positive dynamics were observed in the changes in angina functional class. At the baseline, all patients had angina III FC, in the long term, 3 patients had II FC, 11 patients had I FC, and 6 patients had no angina. Clinical outcomes (mortality, recurrent myocardial infarction, stroke) were absent during the follow-up period. There were two cases of repeated myocardial revascularization. Regression analysis revealed that SYNTAX score was associated with the clinical outcome "repeated revascularization." TMLR in combination with intramyocardial injection of ABMSC is a safe method to achieve a statistically significant antianginal effect and reduce the need for "nitrates," which in turn improves the quality of life and reduces the frequency of hospitalizations due to coronary artery disease. These results can be achieved with strict adherence to the certain indications for the intervention.
... It has been previously demonstrated that TMR may increase the risk of postoperative heart failure, and the purported mechanism includes inflammatory reaction, edema, or reversible myocardial injury. 29,32 Regardless of the mechanism, the potential for TMR-induced heart failure remains a concern that should be studied further so that the risk-benefit ratio of TMR can be better delineated. Overall, the results at this time suggest that there may be a small increase in risk of decreased left ventricular function within the first year. ...
... It has been previously demonstrated that TMR may increase the risk of postoperative heart failure, and the purported mechanism includes inflammatory reaction, edema, or reversible myocardial injury. 29,32 Regardless of the mechanism, the potential for TMR-induced heart failure remains a concern that should be studied further so that the risk-benefit ratio of TMR can be better delineated. Overall, the results at this time suggest that there may be a small increase in risk of decreased left ventricular function within the first year. ...
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... All participants gave written informed consent pre-operatively. Seventy consecutive patients with left ventricular ejection fraction (LVEF) lower than 35% [13, 14] who were selected for elective isolated CABG, enrolled in a randomized , double-blind, placebo controlled trial at Shariati Hospital. Patients who underwent emergency CABG, those with myocardial infarction (MI) or ventricular arrhythmias within 72 hours before the operation, and those requiring inotropic support prior to the surgery were excluded. ...
Myocardial dysfunction needing inotropic support is a typical complication after on-pump cardiac surgery. In this study, we evaluate the effect of milrinone on patients with ventricular dysfunction undergoing coronary artery bypass graft (CABG).
Seventy patients with impaired left ventricular function [left ventricular ejection fraction (LVEF) < 35%] undergoing on-pump CABG were enrolled. Patients were randomized to receive either an intraoperative bolus of milrinone (50 microg/kg) or saline as placebo followed by a 24-hour infusion of each agent (0.5 microg/kg/min). Hemodynamic parameters and transthoracic echocardiographic measurement of systolic and diastolic functions were the variables evaluated.
Serum levels of creatine phosphokinase (CPK), the MB isoenzyme of creatine kinase (CK-MB), occurrence of myocardial ischemia or infarction, and mean duration of using inotropic agents were significantly lower in the milrinone group (p < 0.05). There were no significant differences between the two groups regarding the development of ventricular arrhythmia, duration of cardiopulmonary bypass, intra-aortic balloon pump and inotropic support requirement, duration of mechanical ventilation, duration of intensive care unit stay and mortality rate. Although mean pre-operative LVEF was significantly lower in the milrinone group, there was no significant difference between post-operative LVEFs.
We suggest that perioperative administration of milrinone in patients undergoing on-pump CABG, especially those with low LVEF, is beneficial.
... näle aufzeigten (56,98), seit den sechziger Jahren immer mehr vernachlässigt (117) sorgt werden, da die Koronargefäße oftmals intraoperativ größer sind, als sie präoperativ in der Coronarangiographie erscheinen (74). ...
Diese Arbeit befaßte sich mit den Auswirkungen der TMLR.
Zum Einsatz kam ein CO2-Laser in einem procinen Modell mit prolongier-ter Ischämie. Nach Anlage einer hochgradigen LAD-Stenose wurden die Ausgangswerte erhoben und die Tiere in eine von drei Gruppen randomi-siert: Tiere der Ischämiegruppe (n=10) erhielten keine Therapie, Tiere der Lasergruppen (jeweils n=10) wurden mit TMLR behandelt (Lasergruppe 1: 1 Kanal/cm2; Lasergruppe 2: 2 Kanäle/cm2). Nach drei Monaten wurden die oben genannten Parameter erneut erhoben.
Direkt nach TMLR stiegen die Enzymaktivitäten (p<0,05), es zeigte sich eine Reduktion des LVSWI (12,09±3,82 Gruppe1; 8,81±1,62 Gruppe2; p<0,05) und eine verminderte SMS im LAD-Versorgungsgebiet (70,4±10,0 Gruppe1; 34,8±9,7 Gruppe2; p<0,05). Nach drei Monaten zeigten die gelaserten Tiere eine gerin-gere Aktivität der LDH (93,83±9,83Gruppe1; 99,84±12,04 Gruppe2; p<0,05) und a-HBDH (59,09±11,67 Gruppe1; 70,29±8,67 Gruppe2; p=0,012), verbesserte RVSWI- (5,09±1,06 Gruppe1; 2,87±0,47 Gruppe2; p<0,05), MVO2- (260,7±67,71 Gruppe1; 277,58±108,75 Gruppe2; zur Ischämie: p=0,001) und RMBF-LAD/LCx-Werte (37,98±14,89 Gruppe1; 43,65±15,83 Gruppe2; zur Ischämie: p<0,05), die über den Werten der Ischämiegruppe (45,9±9,36 MVO2, 14,93±11,95 RMBF-LAD/LCx) lagen.
Gruppe 1 zeigte nach drei Monaten einen verbesserten LVSWI (p=0,036). SMS im LCx-Gebiet war in Gruppe 2 nach drei Monaten deutlich besser als in den anderen experimentellen Gruppen (p=0,001). Der RMBF in Gruppe 2 nahm dagegen ab (p<0,05). Der RMBF im LCx-Versorgungsgebiet änderte sich erwartungsgemäß nicht (p=n.s.).
Dieses procine Modell mit prolongierter regionaler Ischämie zeigte die di-rekte Schädigung der Kardiomyozyten nach TMLR mit Erhöhung von En-zymaktivitäten und einer Reduktion der Herzfunktion. Die Langzeitergeb-nisse sind erfolgversprehend, da die Behandlung mit TMLR langfristig er-höhte MVO2-Werte zur Folge hat und das Verhältnis des RMBF verbessert wird.
... Further studies are needed to determine the evolution of the LV contractile function with time after TvL. Although there may be important differences in the effects between transmyocardial and transventricular laser treatment approaches, it is interesting to note that transmyocardial laser treatment of patients with impaired LV function resulted in acute deterioration of the LV function that was reversible within 6 h [16]. ...
Creation of non-transmural myocardial channels by lasers transmitted through endovascular fiberoptics is a novel therapeutic option in the management of patients with coronary artery disease. The acute effect of transventricular laser treatment (TvL) on coronary blood flow, myocardial metabolism and left ventricular function are not well established.
In five anesthetized pigs, flow in the proximal left anterior descending coronary artery (LAD) was reduced and maintained at 70% of baseline. A venous shunt had previously been established draining the hypoperfused region. At 30 min of ischemia, non-transmural myocardial channels were created through the endocardium using a Ho:YAG laser. We measured (a) left ventricular, central venous and arterial pressures, (b) ascending aortic, LAD and coronary venous blood flows, as well as (c) lactate concentration and blood gases in arterial and coronary venous blood, prior to ischemia (baseline), before and 30 min after TvL. Data (given as mean +/- SD) were analyzed with repeated measures ANOVA.
Reduction of LAD blood flow resulted in reduced regional coronary venous blood flow and myocardial oxygen consumption, conversion of regional myocardial lactate uptake to release and adaptation of left ventricular contractility to a lower level. Following transventricular laser, the peak left ventricular systolic pressure declined from 86 +/- 12 to 77 +/- 11 mmHg (P < 0.05), its maximal first positive derivative (LV dP/dt) declined from 900 +/- 221 to 763 +/- 127 mmHg/s (P < 0.05) and the stroke volume decreased from 19.2 +/- 4.1 to 16.4 +/- 5.4 ml (P < 0.05). The changes in regional coronary venous flow, myocardial oxygen consumption and myocardial lactate release after TvL were not significant compared to before TvL. Significant intramural hematomas and tissue destruction were found around the channels at autopsy and by histologic examination.
Transventricular laser treatment of hypoperfused myocardium decreased left ventricular contractility in the acute phase, possibly due to development of perichannel hematomas and disruption of the wall architecture. In addition, TvL did not alter the regional myocardial oxygen supply/demand balance. These results call for caution in the treatment of patients with coronary artery disease by transventricular Ho-YAG laser when there is significant impairment of the left ventricular contractile function.
... In addition, early postoperative myocardial ischemia has been noted to occur relatively frequently post-TMR (18), and yet the possibility of laser treatment as a potential cause of this ischemia has not been described. Patients with preoperative unstable angina and congestive heart failure (1,8,19) have been noted to experience significantly greater post-TMR morbidity and mortality than stable patients. Based on the findings of this study, it seems logical that when laser induced injury is superimposed on significant preexisting left ventricular dysfunction, worsening heart failure with its associated morbidity results. ...
The purpose of this study was to determine the short-term effects of transmyocardial laser revascularization (TMR) on regional left ventricular systolic and diastolic function, myocardial blood flow (MBF) and myocardial water content (MWC).
Clinical studies of TMR have noted a significant incidence of cardiac complications in the early postoperative period. However, the early post-treatment effects of laser therapy on the myocardium and their potential contribution to postoperative cardiac morbidity are unknown.
Swine underwent holmium:yttrium-aluminum-garnet (holmium:YAG) (n = 12) or carbon dioxide (CO2) (n = 12) laser TMR. Regional systolic function for the lased and nonlased regions was quantitated using preload recruitable work area (PRWA) and regional diastolic function with the ventricular stiffness constant alpha.
Preload recruitable work area was significantly decreased in the lased regions both 1 (59.8+/-13.0% of baseline, p = 0.02) and 6 h (64.2+/-9.4% of baseline, p = 0.02) after holmium:YAG TMR. This decreased PRWA was associated with a significant reduction in MBF to the lased regions (13.2% reduction at 1 h, p = 0.02; 18.4% decrease at 6 h post-TMR, p = 0.01). These changes were not seen after CO2 laser TMR. A significant increase in MWC (1.4+/-0.3% increase with holmium:YAG, p = 0.004; 1+/-0.2% increase with CO2, p = 0.002) and alpha (217.4+/-44.2% of baseline 6 h post-holmium:YAG TMR, p = 0.05; 206+/-36.7% of baseline 6 h post-CO2 TMR, p = 0.03) was seen after TMR with both lasers.
In the early postoperative setting, impaired regional systolic function in association with regional ischemia is seen after TMR with a holmium:YAG laser. Both holmium:YAG and CO2 lasers are associated with increased MWC and impaired diastolic relaxation in the lased regions. These changes may explain the significant incidence of early postoperative cardiac morbidity. The impact of these findings on anginal relief and long-term outcome are not known.
Aim ― to reveal the immediate results of the transmyocardial laser revascularization (TMLR) using CO2-laser along with the intramyocardial injections of autologous bone marrow stem cells (ABMSC) in patients with end-stage coronary lesions who cannot be completely revascularized with either percutaneous catheter intervention (PCI) or coronary artery bypass graft surgery (CABG).
Materials and Methods ― There were 20 patients with coronary artery disease (CAD) (mean age 55.4±8.6 years; data presented as mean with standard deviation – M±SD) enrolled in this prospective observational study. 90% were men. All were in angina NYHA class III. Arterial hypertension was presented in 90%, peripheral atherosclerosis in 60%. Other 60% of the patients were post-myocardial infarction, 70% were current smokers and the mean SYNTAX Score was 45.7±12.4. All patients had normal left ventricular ejection fraction and volumes calculated echocardiographycally. Around the zone of CO2-laser impact were injected ABMSC concentrate 200 μl per injection.
Results ― All surgeries done off-pump via left-sided anterolateral thoracotomy approach and CO2-laser with the mean duration of 114±41 minutes. Magnetic resonance imaging data was compared to the left ventricle (LV) wall segments to perform the laser holes. A sign of transmural perforation was the blood jet from the holes in the LV wall. We executed 24±5 perforations and injected 91.5 (67, 115) mln of ABMSC (data presented as median with interquartile range) per patient. Perforations performed on the lateral, anterior and posterior LV walls in 95%, 85% and 45% respectively and on the apex in 60%. The number of the holes did not prolong the time of the surgery (r=–0.09; Spearman correlation). Three (15%) patients had non-fatal complications in the early postoperative period. There was no correlation between these complications and the baseline clinical characteristics or intraoperative parameters. Mortality was 0%. Length of the intensive care unit stay was 1 day and total hospital stay was 6.7±0.7 days (M±SD).
Conclusions ― TMLR with intramyocardial autologous stem cells injections in patients with end-stage CAD is safe. This procedure can be done in the most severe group of patients who cannot be completely revascularized with either PCI or CABG surgery. Futher investigation is needed to assess the effectiveness of the procedure.
The A.N. Bakoulev Scientific Center for Cardiovascular Surgery has a long experience of operations transmyocardial laser revascularization (TMLR). So TMLR procedure, alone or in combination with CABG, there are more than 1160 operations, from 2010, carried out 20 operations TMLR combined with the intramyocardially introduction of ASCM and 72 patients TMLR in combination with intramyocardial introduction ASCM in addition to CABG. The purpose - to reveal the immediate results of the transmyocardial laser revascularization (TMLR) using CO2-laser along with the intramyocardial injections of autologous bone marrow stem cells (BMSC) in patients with end-stage coronary lesions who cannot be completely revascularized with either percutaneous catheter intervention or coronary artery bypass graft surgery. Materials and methods. There were 20 patients (mean age 55.4 ± 8.6 years) enrolled in this prospective observational study. 90% were men. All were in angina NYHA class III FC. Arterial hypertension was presented in 90%, peripheral atherosclerosis in 60%. Other 60% of the patients were post MI, 70% were current smokers and the mean SYNTAX Score was 45,7 ± 12,4. All patients had normal LV EF (64,5%) and volumes calculated echocardiographycally. Around the zone of CO2-laser impact were injected concentrate ASCM 200 ml per injection. Results. All surgeries done off-pump via left-sided anterolateral thoracotomy approach and CO2-laser (Cardiolaser, Russian Federation) with the mean duration of 114 ± 41 min. MRI data was compared to the LV wall segments to perform the laser holes. A sign of transmural perforation was the blood jet from the holes in the LV wall. We executed 24 ± 5 perforations and injected 91,5-106 (67; 115) ml of BMSC concentrate per patient. Perforations performed on the lateral, anterior and posterior LV walls in 95%, 85% and 45% respectively and on the apex in 60%. The number of the holes did not prolong the time of the surgery ( r = -0,09, Spearman correlation). Three (15%) patients had non-fatal complications in the early postoperative period. There was no correlation between these complications and the baseline clinical characteristics or intraoperative parameters. Mortality was 0%. Length of the ICU stay was 1 (1; 1) day and total hospital stay was 6,7±0,7. Conclusion. TMLR with intramyocardial autologous stem cells injections in patients with end-stage CAD is safe. This procedure can be done in the most severe group of patients who cannot be completely revascularized with either PCI or coronary artery bypass graft surgery. Futher investigation is needed to assess the effectiveness of the procedure.
Treatment of patients with chronic severe angina that is refractory to conventional medical treatment, percutaneous coronary intervention or coronary artery bypass grafting (CABG) can present particular challenges. One possible further treatment option is the use of transmyocardial revascularization (TMR), either alone or combined with CABG, for a certain sub-group of these patients.
Die transmyokardiale Laserrevaskularisation ist ein chirurgisches Therapieverfahren, das als ultma ratio bei Patienten mit schwerster diffuser koronarer Herzerkrankung eingesetzt wird. Es führt bei der Mehrzahl der operierten Patienten zu einem signifikanten Rückgang des Angina-pectoris-Syndroms und einer deutliche Steigerung der physischen Leistungsfähigkeit. Dieser Effekt hält offensichtlich mehrere Jahre an. Nach unseren Erfahrungen ist eine transmyokardiale Laserrevaskularisation dann relativ gefahrlos wiederholbar. Eine Zunahme der Myokardperfusion oder der myokardialen Kontraktilität in den laserbehandelten Arealen konnte bislang nicht sicher nachgewiesen werden. Ebenso wurde bislang nicht belegt, daß die myokardiale Kontraktilität in den TMLR-Gebieten postoperativ ansteigt. Eine präoperativ bestehende Diabetes mellitus ist möglicherweise ein Risikofaktor für eine erhöhte Sterblichkeit im ersten Jahr nach TMLR und eine geringere Wahrscheinlichkeit, von der Operation hinsichtlich des Angina-pectoris-Syndroms zu profitieren. Im Einklang mit zahlreichen anderen Arbeitsgruppen gehen wir nach histologischer Analyse der Herzen verstorbener TMLR-Patienten davon aus, daß sich transmyokardiale Laserkanäle im frühen postoperativen Verlauf wieder verschließen. In der Umgebung der Laserkanäle setzt in der Folgezeit eine ausgeprägte Angioneogenese ein, die möglicherweise durch den spezifischen Effekt der Laserstrahlung mitunter ein erhebliches Ausmaß erlangen kann. Diese Angioneogenese könnte durchaus den Hauptwirkmechanismus der TMLR darstellen. Durch eine TMLR mit dem CO2-Laser kommt es nicht zu einer nennenswerten Zerstörung von kontraktilem Myokard.
Objective - There is no obvious explanation, except placebo, to the symptomatic effect of transmyocardial laser revascularization (TMR) in patients with refractory angina. Whether TMR improves myocardial perfusion or relieves symptoms without altering cardiac function is not clarified. Methods - One hundred patients with refractory angina were randomized 1:1 to TMR (CO2 laser) and medical treatment, or medical treatment alone. Technetium 99m (99mTc)-tetrofosmin myocardial perfusion tomography (SPECT), quantitative myocardial perfusion gated SPECT (QGSPECT), technetium 99m (99mTc) multiple gated acquisition radionuclide ventriculografi (MUGA) and cine-magnetic resonance imaging (cine-MRI) were performed at baseline and after 3 and 12 months. Results - Following TMR, a slight reduction in left ventricular ejection fraction (LVEF) (p < 0.05) was observed (MUGA and QGSPECT) compared to baseline. Inclusion of incomplete studies (QGSPECT) revealed a significant reduction in LVEF and increase in left ventricu...
Background: Patients with therapy refractory angina pectoris constitute a problem group, not amendable by conventional treatment. Transmyocardial laser revascularization (TMR) offers a new therapeutic option. The purpose of this study was to evaluate the safety and clinical efficacy of TMR.
Methods: TMR was performed in 40 patients using a new Holmium: YAG laser. In 24 patients TMR (only) was performed with an average of 24 channels/patient. Ninety six percent of these patients had already undergone at least one prior coronary artery bypass grafting procedure (CABG). In 16 patients a CABG in combination with TMR was performed. In this group 25 % had already undergone at least one prior CABG-procedure and received an average of 17,3 channels/patient.
Results: All patients demonstrated a significant improvement in angina pectoris and an average decrease in two CCS-classes, leading to an improvement of exercise capacity by 21 %. With regard to the above parameters there was no difference between TMR and TMR+CABG. Postoperatively, one patient died following acute myocardial infarction (only TMR). Other complications were wound infections (n=7,5 %) and pneumonias (n=5 %).
Conclusions: This study clearly demonstrates that TMR with a new Holmium: YAG laser is a safe method with low perioperative mortality. It is effective in relieving anginal pain and increasing quality of life in patients with severe coronary artery disease.
IntroductionBackground
Lasers used for TMRClinical applications of TMRProcedural morbidity and mortalityRisk factors for morbidity and mortality following TMRRecommendations for TMR as sole therapyRecommendations for TMR as an adjunct to CABGReferences
The increasing numbers of patients with refractory angina and coronary disease unamenable to traditional methods of revascularization has led to the emergence of new therapeutic approaches. Current data indicate that laser transmyocardial revascularization (TMR), typically requiring open thoracotomy, may provide these patients with improvements in angina class and myocardial perfusion. Recently, a percutaneous, catheter-based myocardial revascularization procedure has been developed with laser technology that permits the creation of channels from the endocardial surface of the left ventricle. This procedure has been evaluated in a pilot study of 30 patients with Canadian class III–IV angina and coronary artery disease unamenable to traditional methods of revascularization. The results demonstrated that the clinical application of percutaneous myocardial revascularization (PMR) is safe, and preliminary data indicate that the majority of patients experienced significant improvement in anginal symptoms. An ongoing multicenter randomized study is comparing PMR with conventional medical therapy in patients with severe, refractory angina, evidence of reversible ischemia, and contraindications to angioplasty or bypass surgery.
Transmyokardiale Laserrevaskularisation (TMLR) und linksventrikuläre Reduktionsplastik nach Dor (LVR) sind zwei neue chirurgische Verfahren, die bei Patienten mit austherapierter koronarer Herzkrankheit (KHK) bzw. inksventrikulärer Dilatation oder Herzwandaneurysmen Anwendung finden. Da für diese beiden Patientengruppen ein erhöhtes Risiko für plötzlichen Herztod bekannt sind und die genannten Operationsverfahren arrhythmogene Eigenschaften haben können, wurde in der vorliegenden Studie die Auswirkung dieser Verfahren mit der Inzidenz und Schwere von ventrikulären Arrhythmien, Veränderungen der Herzfrequenzvariabilität (HRV), Veränderungen der ST-Strecke und der QTD verglichen. Als Vergleichsgruppe wurden Patienten gewählt, die eine Bypassoperation erhielten. Präoperativ und eine Woche nach der Operation wurden bei 69 Patienten Langzeit-EKGs und 12-Kanal-
EKGs aufgezeichnet. Postoperativ zeigte sich bei den MLR-Patienten eine signifikante Zunahme von ventrikulären Tachykardien (³ 4 aufeinander folgende ventrikuläre Extrasystolen) von 0% auf 26%, p < 0,05. Ein Patient verstarb postoperativ während der Aufzeichnung des Langzeit-EKGs an Kammerflimmern. Ein Zusammenhang zwischen Höhe der CK- und CKMB-Werte oder der Lage der Laserkanäle konnte nicht festgestellt werden. Im Gegensatz zur TMLR beeinflussten LVR und Bypassoperation das Auftreten von ventrikulären Arrhythmien nicht wesentlich, zeigten aber eine signifikante Verringerung aller wichtigen HRVParameter.
Somit zeigt diese Studie, dass in der frühen postoperativen Phase nach TMLR das Risiko für ventrikuläre Tachykardien und plötzlichen Herztod erhöht ist, während die HRV unbeeinflußt bleibt. Im Gegensatz dazu führen LVR und Bypassoperation zu einer eindrucksvollen Verringerung der HRV-Parameter, die auch noch eine Woche nach Operation nachweisbar ist. Spontane ventrikuläre Arrhythmien bleiben dagegen von diesen letztgenannten Verfahren weitgehend unbeeinflußt.
Transmyocardial laser revascularization for angina relief and intramyocardial autologous endothelial progenitor cell injection for neoangiogenesis may offer a new treatment strategy for patients with intractable ischemic heart disease.
Transmyocardial laser revascularization and intramyocardial injection of bone marrow-derived CD133+ cells was performed in six highly symptomatic patients. Transmyocardial laser channels were created and isolated CD133+ cells were injected intramyocardially. All patients were followed up for a minimum of 6 months postoperatively.
One patient died shortly after the operation due to refractory heart failure. In the five survivors, CCS class improved as well as left ventricular ejection fraction. Left ventricular end-diastolic volume and myocardial perfusion varied between the patients. All patients described a considerable improvement in quality of life postoperatively. Repeated 24-hour Holter monitoring revealed no significant arrhythmias.
In this small patient cohort, intramyocardial CD 133+ cell injection combined with transmyocardial laser revascularization led to an improvement in clinical symptomatology in all patients and in left ventricular function in 4 out of 5 patients, with an unclear effect on myocardial perfusion. Caution is advised when employing this therapy in patients with severely depressed left ventricular function.
Einleitung. Da der Wirkmechanismus der neuen indirekten Revaskularisationsmethode TMLR nicht vollständig geklärt ist, wurden deren Effekte anhand eines akuten porcinen Tiermodells evaluiert.
Methoden. Zur TMLR kam ein CO2-Laser zum Einsatz. Die Evaluierung erfolgte anhand makroskopischer Infarktgrößenbestimmung (Evansblau- und TTC-Färbung), Histopathologie (LFB, HE, TUNEL), Gewebswasseranalyse und klinisch-chemischer Enzymdiagnostik (LDH, a-HBDH, CK, CKMB, Myoglobin, cTropI).
Ergebnisse. Makroskopie: TMLR kann bei RIVA-Ligatur die Ausbildung nekrotischer Areale innerhalb des Risikoareales reduzieren. TMLR im nicht-ischämischen Myokard führt zu makroskopisch sichtbaren fokalen Schädigungen. Histologie: Die Kanäle bleiben bis sechs Stunden nach TMLR offen. Es zeigte sich eine Lumenreduktion um durchschnittlich 51,7 und eine ca. 250 µm breite thermische Schädigungszone mit laserinduzierten DNA-Strangbrüchen in der Nekrosezone. Verbindungen der Kanäle zum linken Cavum und nativen Gefäßen konnten dargestellt werden. Evansblaupartikel in den Kanälen bei Unterbindung des RIVA beweisen einen Anschluß an das Cavum. Fibrinablagerungen in den Kanälen und eine granulozytäre Einwanderung im angrenzenden Gewebe waren zu beobachten. Ödembildung resultierte aus der RIVA-Ligatur sowie TMLR im nicht-ischämischen Myokard, verstärkt bei Kombination von RIVA-Ligatur und TMLR. Klinisch-chemische Diagnostik: Es ergaben sich vergleichbare Anstiege der Ischämiemarker im Serum aller experimentellen Gruppen, auch bei TMLR im nichtischämischen Myokard.
Schlußfolgerung. Die Reduktion der Nekroseausbreitung im Risikoareal ergibt sich aus einer Mikroperfusion über die Kanäle, einer Senkung des O2-Bedarfs durch Ablation myokardialen Gewebes und Induktion einer kontraktilen Dysfunktion. Im Zuge einer Entzündungsreaktion werden die Mikrokanäle zunehmend mit Fibrin verschlossen. TMLR führt zu Steigerung der kardiomyozytären Membranpermeabilität mit Ödembildung und konsekutiver Enzymfreisetzung.
Einleitung: An einem porcinen Modell der chronischen myokardialen Ischämie wurden die Wirkungen unterschiedlicher intramyokardialer Wachstumsfaktortherapien auf die globale Herzfunktion untersucht.
Methoden: Eine Woche nach Anlage einer hochgradigen RIVA-Stenose an Schweinen Deutscher Landrasse wurden Baseline-Daten der Hämodynamik (CO, CI, MAP, HR, LVP) bestimmt und zur Berechnung von dP/dtmax/min sowie LVSWI und RVSWI benutzt. Außerdem wurde der Stenosegrad mittels Angiographie verifiziert. Anschließend erhielten die Tiere intramyokardiale Injektionen mit 0,5 mg FGF-2-Protein (n=6), 2 mg VEGF121-Plasmid-DNA (n=7) oder 2 mg FGF-2-Plasmid (n=7). Nach Ablauf von drei Monaten wurden erneut alle Parameter bestimmt und mit den Baseline-Werten verglichen. Die Ergebnisse wurden einer ischämischen Kontrollgruppe (n=7), die keine Therapie erhielt, gegenübergestellt.
Ergebnisse: Die hochgradige RIVA-Stenose blieb während des dreimonatigen Beobachtungszeitraums unverändert. Während die Druckanstiegsgeschwindigkeit dP/dtmax in der Ischämiegruppe in dieser Zeit abfiel, ließ sich durch die Therapie in den beiden FGF-2 und VEGF-Gruppe ein Erhalt der Funktion erreichen. Die FGF-2- und VEGF-Plasmidbehandlungen führten dabei im Vergleich zur unbehandelten Ischämiegruppe zu besseren Ergebnissen. Für dP/dtmin ließ sich nach drei Monaten keine Abweichung zur Baseline feststellen. Beim LVSWI kam es nur in der FGF-2-Proteingruppe zu einer Verschlechterung. Der RVSWI fiel in allen Gruppen ab, Unterschiede zwischen den Versuchsansätzen ließen sich nicht nachweisen.
Schlussfolgerung: In dem hier verwendeten Modell führte die intramyokardiale Injektion von VEGF121- und FGF-2-Plasmid-DNA im Vergleich zu einer FGF-2-Proteininjektion in Bezug auf die Kontraktilität zu besseren Ergebnissen. Diese beiden Behandlungen erscheinen daher als geeignet zur Therapie der chronischen myokardialen Ischämie.
Die Induktion einer Revaskularisation durch angiogenetisch wirksame Wachstumsfaktoren bei Patienten mit kardiovaskulären Erkrankungen zeigt heute vielversprechende Ansätze. Das Ziel unserer Studie war, die Auswirkung einer Therapie mit FGF-2 und VEGF-A121 auf das Gefäßwachstum (Angio- und Arteriogenese) bei chronischer Myokardischämie im porcinen Modell zu untersuchen.
Methoden: Eine Woche nach Anlegen einer hochgradigen, proximalen RIVA-Stenose erfolgte eine intramyokardiale Applikation von 500 µg rhFGF-2 (n = 6), 2 mg phFGF-2 (n = 7), 2 mg phVEGF-A121 (n = 6) und einer Pufferlösung als Placebo (n = 3) in das ischämische Areal. Als weitere Kontrollen dienten nicht therapierte ischämische (n = 5) und gesunde Tiere (n = 5). Drei Monate später erfolgte nach immunhistochemischer Doppelfärbung mit dem Anti-von-Willebrand-Faktor und dem Anti-Smooth-Muscle-Actin eine Quantifizierung der Kapillaren und Arteriolen.
Ergebnisse: In allen Therapiegruppen konnten wir eine signifikante Steigerung der Kapillardichte im Vergleich zu der ischämischen Kontrollgruppe zeigen (p = 0,009 vs. rhFGF-2; p = 0,003 vs. phFGF-2; p = 0,017 vs. phVEGF-A; p = 0,036 vs. Placebo). Einen Unterschied zwischen den Gruppen und gegenüber den gesunden Tieren konnten wir allerdings nicht feststellen. Eine Therapie mit rhFGF-2 und phFGF-2 verursachte ferner eine signifikante Steigerung der Arteriolendichte im Vergleich zur ischämischen Kontrollgruppe (beide p = 0,003). Darüber hinaus war die in der phFGF-2-Gruppe ermittelte Arteriolendichte verglichen mit den gesunden Tieren ebenfalls signifikant erhöht (p = 0,03). Eine phVEGF-A-Applikation verfehlte dagegen knapp das Signifikanzniveau gegenüber der Ischämie (p = 0,052). Zwischen den Therapiegruppen bestanden auch bezüglich der Arteriolendichte keine Unterschiede.
Zusammenfassung: In einem porcinen Modell chronisch myokardialer Ischämie steigert eine Therapie mit FGF-2 unabhängig von seiner Applikationsform (Protein oder Plasmid) sowohl die Kapillar-, als auch die Arteriolendichte. Eine Plasmid-vermittelte VEGF-A121-Therapie bewirkt ausschließlich eine Zunahme der Kapillaren. Unsere Ergebnisse konnten die Theorie bestätigen, daß VEGF eine Angiogenese unterstützt, während FGF-2 neben einer Angiogenese auch eine Arteriogenese induziert.
Diese Arbeit wurde durchgeführt, um die Auswirkungen einer Therapie mit TMLR und intramyokardialer (i.m.) Verabreichung von Wachstumsfaktoren auf die regionale und die globale Funktion zu analysieren.
Zum Einsatz kamen ein CO2-Laser und die Wachstumsfaktoren bFGF und phVEGF121 in einem porcinen Modell chronisch myokardialer Ischämie. Eine Woche nach Anlage einer hochgradigen, proximalen RIVA-Stenose wurden die Schweine - nach Bestimmung der regionalen (SMV) und der globalen Funktion (dP/dt und LVSWI) in Ruhe und unter Dobutamin-Streß - in eine von 3 Gruppen randomisiert: Bei Tieren der ischämischen Kontrollgruppe (n=7) erfolgte keine Therapie, Tiere der TMLR+FGF-Gruppe wurden mit TMLR und i.m.-Injektion von 300µg bFGF-Protein behandelt (n=7), die der TMLR+VEGF-Gruppe mit TMLR und 2mg phVEGF (cDNA) (n=7). Nach 3 Monaten wurden die oben genannten Parameter in einer 3. Operation erneut bestimmt.
Nach 1 Woche Ischämie war die SMV in aller Gruppen im RIVA-Gebiet auf gleichem Niveau (12,6 vs. 11,75 vs. 11,0). Zum Ende der Studie verbesserte sich die SMV der behandelten Gruppen auf 18,3 (FGF) bzw. 19,1 (VEGF) versus 13,0 in der Kontrollgruppe (p=0,03).
Die dP/dtmax-Werte lagen bei der 2. OP in der Kontrollgruppe bei 1323, in der FGF-Gruppe bei 1101 und in der VEGF-Gruppe bei 1106 mmHg/s. 12 Wochen später ergaben sich folgende Werte: 1042 (p=ns.), 1256 (p=ns.) und 1412 (p=0,02) mmHg/s.
Der LVSWI änderte sich in den therapierten Gruppen im Dreimonatszeitraum nicht (FGF-Gruppe: 14,2 vs. 14,5 (p=ns.) und VEGF-Gruppe: 11,8 vs. 12,3 mJ/kg KG (p=ns.)). In der Kontrollgruppe dagegen verschlechterte sich der LVSWI von 13,0 auf 9,1 mJ/kg KG (p=0,018).
Dieses Modell chronisch-regionaler Ischämie zeigt, daß die CO2-Laserrevaskularisaton kombiniert mit direkter i.m.-Applikation der Wachstumsfaktoren bFGF bzw. phVEGF121 die regionale Kontraktilität in Ruhe und unter Streß signifikant steigert, und die globale Funktion zumindest relativ zur ischämischen Kontrolle verbessert.
Histologic examination of the human myocardium has been performed several days, weeks, and months after transmyocardial laser revascularization. We performed microscopic examinations 2 hours postoperatively. In addition to the patent channel (diameter, 1 mm) and a 1-to 2-mm rim of necrosis, a 1- to 3-mm zone of myofibrillary degeneration was found. This additional reversible injury immediately after transmyocardial laser revascularization could explain the higher mortality rate in patients with reduced left ventricular function.
The clinical experience with transmyocardial laser revascularization indicates that angina is relieved significantly, perfusion and treadmill tolerance are improved and hospital admissions are decreased. The exact mechanism for a laser revascularization linked improvement is still unknown. Transmyocardial laser revascularization should be used only in highly selected cases when conventional methods fail to improve patients symptoms. Further evaluation of the efficacy of the new indirect revascularization method in clinical (larger multicenter trials) and experimental studies to elucidate the mechanism of TMLR is warranted. Experimental long-term studies to explain the mechanism are in progress.
This experimental study was initiated to determine whether transmyocardial laser revascularization (TMLR) after acute myocardial ischemia may improve clinical chemistry and diminish the amount of necrosis. In addition, the influence of TMLR on healthy myocardium was analyzed.
The prolonged short-term effectiveness of TMLR was evaluated in 44 open-chest anesthetized pigs with (n = 21) or without (n = 23) the setting of acute myocardial ischemia (observation period 6 h): seven pigs served as controls (thoracotomy only). An additional seven pigs had left anterior descending artery (LAD) occlusion only (ischemia group). A subsequent 14 pigs were treated by TMLR (CO2) prior to LAD occlusion: Seven pigs received one laser channel/cm2 (group 1) and in seven pigs two channels/cm2 in the LAD territory (group 2) were performed. In addition, 16 pigs underwent TMLR without ischemia: Eight pigs received one channel/cm2 (group 3) and eight pigs two channels/cm2 (group 4). Clinical chemistry, histo-chemical assessment and histology were performed.
TMLR limits the expansion of the myocardial infarction zone: laser group 2 indicated a significant smaller area of necrosis in the area at risk (ischemic group (31%) vs. laser group 1 (19%), P = ns; laser group 2 (7%) vs. ischemic group, P < 0.01; laser group 1 vs. 2, P < 0.01). The amount of the area of necrosis and ischemia of laser groups 3 and 4 compared with control did not differ significantly (P = ns). Preventive creation of microchannels before ischemia did not diminish ischemic parameters (P = ns). The myocardial water content-measurements (MWC) in the ischemia, laser 1 and 2 groups did not show any difference at the end of the experiment, except higher values of laser group 2 (P < 0.05). Laser groups 3 and 4 revealed significantly higher MWC values compared with control (P < 0.001).
This prolonged acute study demonstrates that CO2-TMLR significantly reduces the amount of necrosis in the area at risk, but does not reduce cardiac ischemic markers. In healthy myocardium, TMLR significantly increases myocardial water content and ischemic parameters and induces small ischemic and very small necrotic areas surrounding open laser channels. Generally, the elevated cardiac enzymes and proteins are mainly attributed to the expected rise caused by vaporization of myocardial tissue in all laser groups.
Clinical studies have demonstrated a significant reduction of cardiac index shortly after transmyocardial laser revascularization in patients with low ejection fraction. We analyzed the influence of transmyocardial laser revascularization on healthy myocardium in pigs.
Carbon dioxide channels were created in 20 pigs which were observed for 6 hours. Ten pigs received one laser channel and ten pigs two laser channels per cm2 in the left anterior descending artery region. Seven pigs served as controls. Perfusion (microspheres), function, histochemical, and histologic assessments were subsequently performed.
A significant deterioration of left ventricular stroke work index was observed shortly after transmyocardial laser revascularization in both laser groups (p < 0.05). After 6 hours the left ventricular stroke work index did not increase and showed significantly reduced values at rest (p < 0.05) and during stress in the laser groups (p < 0.01). Normal regional perfusion, small ischemic and necrotic areas, open laser channels in the left anterior descending artery region and significantly increased myocardial water content were observed in the laser groups (p < 0.01).
Carbon dioxide laser channels significantly decrease global heart function shortly after transmyocardial laser revascularization in healthy porcine myocardium. This myocardial tissue showed no recovery 6 hours postoperatively.
For those of us old enough to remember what in the 1960s was known as ‘the Congo crisis’ ‐ soon to become the ‘endless crisis'‐ the tragic singularity of the present conjuncture is perhaps less apparent than some of the contributions to this special issue on the Congo might suggest. No one who lived through the agonies of the Congo's improvised leap into independence ‐ followed by the swift collapse of the successor state and the break‐up of the country into warring fragments ‐ can fail to note the analogy with the dismemberment of the Mobutist state in the wake of the 1998 civil war. Then as now the former Belgian colony was faced with a crisis of statelessness of huge proportions. The challenges confronting the international community today are in a sense remarkably similar to what they were in the early 1960s. How to reconstruct a broken‐backed polity, how to rebuild an army reduced to a rabble by the emergence of armed factions, how to revitalise basic human services, ensure a minimum of security and economic self‐sustenance; in short, how to restore the legitimacy, territorial integrity and internal sovereignty of the state, such are the daunting challenges facing the international community. This is not meant to suggest that history repeats itself, only that historical perspectives can offer important clues to an understanding of the present.
Myocardial revascularisation by laser is an emerging treatment for refractory angina in patients with coronary artery disease that is not amenable to conventional revascularisation. With the original technique, laser energy was applied to epicardial surface of the heart through a lateral thoracotomy; so-called transmyocardial laser revascularisation (TMR). It is now possible, using catheter-based percutaneous myocardial revascularisation (PMR) to deliver laser energy to the myocardium via the endocardial surface. In this article we discuss the possible mechanism of action of laser revascularisation, and summarise the results of recent randomised controlled trials of TMR, PMR systems are described, and the growing evidence for their efficacy is reviewed.
The clinical and experimental data relevant to the theoretical mechanisms and clinical results of laser myocardial revascularization are reviewed. Both transmyocardial and percutaneous approaches are considered. Both types result in a reduction in anginal symptoms in patients refractory to conventional therapy and are likely to act through common pathways. The proximate mechanisms for the transmyocardial revascularization effect most likely relate to myocardial inflammation, secondary stimulation of growth factors, and denervation of the myocardium.
Transmyocardial laser revascularization (TMLR) has been widely evaluated for treatment of the ischemic myocardium either in conjunction with coronary artery bypass grafting or as sole therapy. Clinically, it has shown significant improvement for angina symptoms, but the mechanism by which this modality works is unknown at this time. The original premise on which transmyocardial revascularization was established depended on its ability to essentially generate channels that would directly carry blood from the ventricle into the ischemic myocardium. This theory, however, has not been substantiated, so other mechanisms have been postulated. This article gives a historical perspective on the advent of transmyocardial revascularization and the many animal and human studies that have paved the way for its clinical use. Current controversies are examined, along with the new advances in laser technology and where the future of TMLR is headed.
The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris.
Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published.
One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2.
Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.)
Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.
To evaluate immediate changes in left ventricular wall motion in patients treated using Biosense direct myocardial revascularization laser system.
Regional wall motion in 10 patients undergoing catheter-based direct myocardial revascularization using a holmium:yttrium aluminium garnet laser was assessed by transesophageal echocardiography before and immediately after the procedure.
Mild deterioration in wall-motion score occurred rarely for only three of 160 (1.9%) segments and did not induce clinical heart failure.
With the current catheter-based laser myocardial revascularization strategy, mild deterioration in wall motion of treated segments was rarely observed and did not effect overall left ventricular function or induce clinical congestive heart failure.
Despite the proven effectiveness of coronary bypass surgery and percutaneous angioplasty techniques, an increasing number of patients are presenting with severe, medically intractable angina who are not candidates for either procedure. Two alternative strategies, transmyocardial laser revascularization and exogeneous administration of angiogenic growth factors (therapeutic angiogenesis) are currently being evaluated in such patients. This review focuses on the current status of these two procedures, emphasizing their similarities and differences in order to provide insight into what role each may ultimately play in the management of patients with otherwise unrevascularizable myocardial ischemia.
Does transmyocardial laser revascularization (TMLR), a new surgical technique for treating patients with otherwise intractable angina pectoris, improve myocardial perfusion, metabolism, and, consequently, function?
Patients referred for TMLR, alone or with coronary artery bypass grafting (CABG), were preoperatively evaluated clinically and by treadmill stress testing, echocardiography, ventriculography, radionuclide assessment of perfusion and metabolism, and hemodynamic assessment. Intraoperatively it was decided that some patients only required CABG. Follow-up evaluations were repeated after 6 (n = 40) and 12 months (n = 23) and compared with preoperative values.
CABG only was performed in 35 cases, TMLR + CABG in 17, TMLR only in 45. 1-year mortality was 11% in the TMLR, zero in the TMLR + CABG, and 11% in the CABG groups. In all groups a significantly improved CCS angina- and NYHA class was observed immediately after operation and after 6 and 12 months. In all study groups treadmill tolerance (p<0.05) improved, but regional and global function, perfusion at rest, and metabolism were not significantly changed at 6 and 12-months follow-ups. Perfusion studies under stress demonstrated an improvement only in the CABG group after 12 months (p<0.05), whereas in both TMLR groups the lasered ischemic segments remained unchanged.
TMLR significantly improves long-term clinical status and treadmill stress tolerance, but appears to have little if any effect upon regional and global function, perfusion, and metabolism.
The clinical and experimental data relevant to the theoretical mechanisms and clinical results of laser myocardial "revascularization" are reviewed. Both transmyocardial (TMR) and percutaneous (PMR) approaches are considered. Special attention is paid to the issue of TMR-induced angiogenesis. Both TMR and PMR result in a reduction in angina symptoms in patients refractory to conventional therapy and are likely to act through common pathways. TMR-induced angiogenesis appears to result from the up-regulation of vascular growth factors. However, the available data suggest that the angiogenic response is not a unique consequence of laser revascularization. Rather, the angiogenesis associated with TMR is likely to be a non-specific response of the myocardium to injury.
The increasing numbers of patients with refractory angina and coronary disease unamenable to traditional methods of revascularization has fed to the emergence of new therapeutic approaches. Current data indicate that laser transmyocardial revascularization (TMR), typically requiring open thoracotomy, may provide these patients with improvements in angina doss and myocardial perfusion. Recently, a percutaneous, catheter-based myocardial revascularization procedure has been developed with laser technology that permits the creation of channels from the endocardial surface of the left ventricle, This procedure has been evaluated in a pilot study of 30 patients with Canadian class III-IV angina and coronary artery disease unamenable to traditional methods of revascularization. The results demonstrated that the clinical application of percutaneous myocardial revascularization (PMR) is safe, and preliminary data indicate that the majority of patients experienced significant improvement in anginal symptoms, An ongoing multicenter randomized study is comparing PMR with conventional medical therapy in patients with severe, refractory angina, evidence of reversible ischemia, and contraindications to angioplasty or bypass surgery. (C) 1999 by Excerpta Medica, Inc.
This experimental study was initiated to determine whether TMLR may prevent porcine myocardium from ischemia and necrosis after acute myocardial infarction. In addition, the influence of TMLR on healthy myocardium was analyzed.
The short-term effectiveness of TMLR was evaluated in 38 open-chest anesthetized pigs with (n = 18) or without (n = 20) acute LAD occlusion (observation period 6 hours): Six pigs served as controls (thoracotomy only). An additional six pigs had LAD occlusion only (ischemic group). A subsequent 12 pigs were treated by TMLR (CO2) prior to LAD occlusion: Six pigs received one laser channel/cm2 (group 1) and in six pigs two channels/cm2 in the LAD territory (group 2) were performed. In addition, 14 pigs underwent TMLR without ischemia: Seven pigs received 1 channel/cm2 (group 3) and seven pigs 2 channels/cm2 (group 4). Pathomorphological assessment and histology were performed.
TMLR limits the expansion of the myocardial infarction zone: laser group 2 demonstrated a significantly smaller area of necrosis in the area at risk (ischemic group (32%) vs. laser group 1 (18%, p = ns) and 2 (8%, p = 0.0076); laser group 1 vs. 2, p = 0.0056). The amount of the area of necrosis of laser groups 3 (0.4%) and 4 (0.04%) compared to control (0%) did not differ significantly (p = ns). Furthermore, in the lased territories of laser groups 3 and 4 microscopic analysis revealed signs of ischemia in 10 +/- 30.9% of all examined histological samples (p = ns vs. control). During a short coronary occlusion the laser-induced tracks were partially filled with blue dye in 94.8 +/- 27.0/85.9 +/- 34.3/94.85 +/- 22.0%/70.21 +/- 47.0% (laser groups 1 - 4 respectively p = ns) The myocardial water content-measurements (MWC) of the ischemia and laser group 1 were not different at the end of the experiment (p = ns). In contrast, laser groups 2, 3 and 4 revealed significantly higher MWC values compared to control (p = 0.036, p < 0.001, p < 0.001; respectively).
This prolonged acute study demonstrates that preventive CO2-laser revascularization significantly reduces the amount of necrosis in the area at risk. Histological examination supported the idea that some pigment gained access to the ischemic tissue via patent channels. In healthy myocardium, TMLR significantly increases myocardial water content and induces non-significant small ischemic and very small necrotic areas surrounding open laser channels.
Background:
Transmyocardial laser revascularization for severe diffuse coronary artery disease reduces angina significantly. The effect on survival, however, is questionable, and risk factors are not adequately addressed. Considering that transmyocardial laser revascularization channels do not remain patent for improving direct myocardial blood supply, other variables such as perfusion through open native or grafted vessels in remote non-transmyocardial laser revascularization areas are probably more important for survival. This hypothesis is the subject of the study.
Methods:
Transmyocardial laser revascularization was performed with a CO2 laser system in 63 patients between October 1995 and December 1997. Patients received transmyocardial laser revascularization alone or in combination with coronary artery bypass grafting. The heart was divided into three perfusion zones as determined by the three major coronary arteries. Patients were divided into three groups according to the number of zones that were perfused by either a native coronary artery or a patent bypass graft: group 1 (n = 9), none; group 2 (n = 24), one; and group 3 (n = 30), two. Follow-up was performed at 3, 6, 12, 24, and 36 months and was 100% complete. Mean latest follow-up was 26.2 months, minimal follow-up of survivors was at least 12 months.
Results:
Overall mortality was remarkably higher in group 1 (77.8%) compared with group 2 (20.8%, p = 0.005) and group 3 (13.3%, p = 0.001). Hospital mortality was 22.2% in group 1, 0% in group 2, and 3.3% in group 3. Late mortality was also higher in group 1 (55.5% versus 20.8%, and versus 9.9%, respectively). Cardiac deaths were more frequent in group 1 (55.5% versus 12.5% in group 2, p = 0.02, and versus 9.9% in group 3, p = 0.009). The number of perfused myocardial zones showed a significant influence for survival (p = 0.002).
Conclusions:
These data give some directional evidence that survival seems to be beneficially affected by the number of nonlasered perfused myocardial zones through native vessels or grafts in patients undergoing transmyocardial laser revascularization.
The purpose of this study was to determine the effect of transmyocardial laser revascularization (TMLR) on myocardial perfusion and function in chronically ischemic myocardium.
In the first operation a stenosis of the left anterior descending artery was created in 20 open-chest anesthetized pigs to implement this ischemic model. In contrast, four pigs served as controls (thoracotomy only). Seven days later (2nd operation), all animals were studied at baseline by analyzing different parameters of perfusion (radioactive microspheres), function, and intramyocardial pressure. Afterwards, pigs who received a left anterior descending artery stenosis were randomized into one of three groups: animals in laser group 1 (n=7) received one and in laser group 2 (n=7) two laser channels per cm(2) in the left anterior descending artery territory. Animals of the ischemic group (n=6) underwent the same procedures without transmyocardial laser revascularization. Three months later, the animals were re-studied (3rd operation) and additional analysis of histochemistry and myocardial water content was performed.
Regional myocardial blood flow (RMBF) in laser group 2 revealed statistically higher RMBF values compared to the ischemic group (0.39+/-0.13 versus 0.14+/-0.12 ml/min/g; P=0.043), after 3 months, whereas the absolute RMBF had not increased compared to the 1-week baseline values. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared to the initial values in all study groups (P=ns). Nevertheless, laser group 1 demonstrated relatively higher LVSWI(max) values compared to the ischemic (1.33+/-0.19 versus 0.93+/-0.16 mJ/kg; P=0.03) and laser group 2 (1.33+/-0.19 versus 1.02+/-0.15; P=0.024). Regional contractility of laser groups 1 and 2 recovered after 3 months (which had deteriorated shortly after transmyocardial laser revascularization) and increased under stress (100% versus 144.33+/-46.42, P=0.029 and 100% versus 116.26+/-21.06, P=0.034; respectively). In contrast, the corresponding ischemic group values were not different from initial values (P=ns).
This model of chronic regional ischemia demonstrates that CO(2)-laser revascularization significantly improves microperfusion and regional function, whereas the overall perfusion and global LV function is unchanged.
There is no obvious explanation, except placebo, to the symptomatic effect of transmyocardial laser revascularization (TMR) in patients with refractory angina. Whether TMR improves myocardial perfusion or relieves symptoms without altering cardiac function is not clarified.
One hundred patients with refractory angina were randomized 1:1 to TMR (CO2 laser) and medical treatment, or medical treatment alone. Technetium 99m (99mTc)-tetrofosmin myocardial perfusion tomography (SPECT), quantitative myocardial perfusion gated SPECT (QGSPECT), technetium 99m (99mTc) multiple gated acquisition radionuclide ventriculografi (MUGA) and cine-magnetic resonance imaging (cine-MRI) were performed at baseline and after 3 and 12 months.
Following TMR, a slight reduction in left ventricular ejection fraction (LVEF) (p < 0.05) was observed (MUGA and QGSPECT) compared to baseline. Inclusion of incomplete studies (QGSPECT) revealed a significant reduction in LVEF and increase in left ventricular end-diastolic volume (LVEDV) (p < 0.05) compared to a control group. Otherwise, no between-group comparisons showed statistically significant differences.
TMR did not improve myocardial perfusion, but led to a reduction in LVEF and increase in LVEDV, however not significantly different from the control group.
In ischemic cardiomyopathy (left ventricular ejection fraction [LVEF] < or = 30%), myocardial revascularization by coronary artery surgery has better results than heart transplantation, provided there is sufficient ischemic but viable myocardium. The mode of action of transmyocardial laser revascularization (TMR) is still being debated, but if the procedure induces improved myocardial perfusion it could be a "bridge," or alternative, to heart transplantation.
We retrospectively analyzed 194 patients, who underwent TMR between July 1997 and October 1999. Patients with TMR as an adjunct to coronary artery surgery (n = 30) and those who did not provide written consent to the procedure (n = 8) were excluded; 126 patients had normal or moderately reduced left ventricular function, and 30 patients with ischemic cardiomyopathy (LVEF < or = 30%) were included.
After 12 months, the Canadian Cardiovascular Society (CCS) score dropped significantly from 3.6 (3 to 4) to 2.4 (1 to 4) and maximum work load increased significantly from 58 W (25 to 100 W) to 73 W (25 to 120 W). However, thallium score and LVEF did not improve significantly (27% [15% to 30%] to 32% [15% to 45%]). Prior to the TMR procedure, all 30 patients had a "low risk" or "medium risk" of death according to the Aaronson classification. The 30-day, 1-year, and 2-year survival rates were 83%, 50%, and 47%, respectively.
We conclude that TMR in ischemic cardiomyopathy (LVEF < or = 30%) has a perioperative risk comparable to that for heart transplantation, but there is no improvement of myocardial performance or life expectancy. Therefore, TMR cannot be regarded as a "bridge," or alternative, to transplantation. However, in individual cases with contraindications for transplantation the anti-anginal effect may justify use of the procedure.
Within the period from 11/1994 to 3/1996 a total of 125 patients underwent isolated transmyocardial laser revascularization with an 800 watt CO2 laser in our institution. All of these patients suffered from severe diffuse coronary disease with class III or IV CCS angina despite maximum antianginal therapy and had previously undergone one or more CABG and/or PTCA procedures. Preoperatively the patients underwent left heart catheterization, echocardiographic wall motion analysis, as well as thallium perfusion scans (SPECT) during exercise. These tests were repeated 3, 6, and 12 month after the procedure. Postoperatively, 71 percent of the patients report a marked decrease in angina pectoris symptoms (mean CCS value was 3.5 preoperatively, 1.9 three months after surgery, and 2.0 six month after TMR) and better physical endurance (ergometric maximal work load increased from a preoperative mean of 55.0 ± 30.7 watts to 76.5 ± 21.8 watts three months after surgery, p<0.05). However, the left ventricular ejection fraction remained unchanged, with 42.5 ± 11.0 % before, 45.1 ± 10.9 % three month, and 45.3 ± 13.4 % six months after TMLR (p=NS). In one half of the patients an improvement in perfusion scans (Th-SPECT) three and six months after surgery was observed. 11 out of these 125 patients died after TMR from different reasons (pneumonia, untreatable ventricular arrhythmia, myocardial infarction, septicemia). Eight patients who died between the 1st and 42nd postoperative day underwent a postmortem examination with histological analysis of the areas treated by TMR. The predominant finding was recently closed channels. In specimens from patients who died several weeks after TMR a high density of capillaries was evident within the closed channels. Our results seem to justify the use of TMLR in patients who presented with urgent indications for myocardial revascularization, although their coronary vessel status did not seem to promise success for aorto-coronary bypass surgery. But in conclusion of histological findings, it seems unlikely, that TMR follows the mechanism of the amphibian heart.
Objectives: For patients with severe angina, in whom PTCA or CABG is impossible, a new Laser treatment technique (transmyocardial laser revascularization=TMLR) has been used for revascularization. Methods: Between 9/95 and 2/96 TMLR was performed in 14 male patients (mean age 68.0±5.5 years) who had demonstrable ischemia in viable myocardium. Preoperative 11/14 patients (79%) had an MI and 9/14 patients (64%) underwent previous CABG. LV-EF was 46% on average. The mean Canadian Cardiovascular Society (CCS) angina class was 3.6±0.6. All patients are followed by PET, 201-TI-SPECT or Tc99m-Sestamibi scan, echo, exercise tolerance test, clinical status and ventriculography - preoperative, 4 and 12 months after operation. Perioperative Swan Ganz catheter - investigations were performed. Results: In 4/14 patients (36%) a combined procedure (TMLR and aortocoronary bypass operation) has been done. In these cases 12.3 microchannels and in the solitary procedures (TMLR in 64%) 28 microchannels per patient (on average) were achieved. One week after operation (n=13) mean CCS angina class was to 2.5±0.8 (p<0.05). At 4 month, (n=6), mean CCS angina class decreased to 1.8±0.6 (p<0.05). Resting perfusion and metabolic, echocardiographic and MUGA-scan- studies did not represent statistically significant change over baseline (p=ns). In contrast average treadmill tolerance and the average maximal exertion were both significantly increased. Conclusions:This study indicates that the treatment with TMLR relieves symptoms and increases treadmill tolerance. Further systematic follow-up will show if myocardial perfusion and contractility will improve. Experimental porcine studies to explain the mechanism of TMLR are in progress.
Methods used to revascularize ischemic myocardium have included arterial reconstruction, coronary artery bypass grafting, providing direct circulation from the intraventricular chamber, and techniques to promote collateral circulation.
Ventricular channels from the epicardial surface through the endocardium are readily made with the CO2 laser. Animal experiments suggest that these channels protect the ischemic myocardium and provide circulation to the muscle from the ventricular chamber.
Clinical use of the CO2 laser in conjunction with aortocoronary bypass grafting is reported in a patient with three-vessel coronary artery disease and total occlusion of the left anterior descending coronary artery (LAD), and hypokinesis of the anterior wall and apex. Following bypass a series of laser channels were made in the hypokinetic area of the left ventricle. Postoperative myocardial Tc PYP scans were within normal limits, including the previously dyskinetic anterior apical area. Serial EKGs remained unchanged from the preoperative status. Creatinine phosphokinase-myocardial band (CPK-MB) was elevated to 6 on the first and second postop day and was 0 from the third day. The patient was not recatheterized.
The technique of myocardial revascularization by laser may be a viable addition to present treatment modalities. Further investigation and long-term follow-up are needed.
Abstract In recent time, it has become more and more probable that patients with severe diffuse coronary artery disease, who are not candidates for aortocoronary bypass surgery or percutaneous transluminal coronary angioplasty procedures, can benefit from transmyo-cardial laser revascularization (TMR). But the underlying principle of TMR still remains unclear. This study reports on a histological analysis of eight patients, in whom a total of 250 channels had been created, who died after TMR. The TMR channels were created by a CO2 laser surrounded by a zone of necrosis with an extent of about 500 μm. In the hearts of patients who died in the early postoperative period (1 to 7 days postoperative), almost all channels were closed by fibrin clots, erythrocytes, and macrophages. There were no obvious connections between the channels and the ventricular cavity. In specimens from patients, who died 2 or more weeks after the procedure, a granular tissue with high macrophage and mono-cyte activity was observable. Within this tissue, we observed a developing network of capillaries. Otherwise, the tissue filling the channels did not substantially differ from scar tissue. We failed to observe connections between the ventricular cavity and the new capillaries. Whether these vessels within the closed channels have any impact on myocardial perfusion remains unclear, but it seems unlikely that the clinical effects of TMR are based on the principle of the amphibian heart.
We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-d-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary arterybypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13 %) was estimated in the segments with no 18F-FDG uptake. Despite the potential limitations due to the semiquantitative analysis of the images, the method appears to provide reliable information for the diagnostic and prognostic evaluation of patients with CAD undergoing CABG and confirms that the identification of hibernating myocardium with 18F-FDG is of paramount importance in the diagnosis of patients undergoing CABG.
The effectiveness of intraaortic balloon counterpulsation is reduced frequently by arterial insufficiency following balloon insertion and occasionally by inability to pass the balloon centrally from a peripheral site. From a series of patients undergoing cardiac catheterization, a subgroup with increased likelihood of needing balloon counterpulsation can be selected. Patients so chosen have received one aortoiliac injection of contrast material at the time of cardiac catheterization. Impressive degrees of vessel irregularity and stenosis on an atherosclerotic basis and of tortuosity of normal lumen size have been noted. Such information, gathered at little additional risk or irradiation, is considered to be important in the subsequent choice of sides for transfemoral insertion and may rule out attempted passage of the balloon by this route, directing the surgeon to a deliberate, prompt, transabdominal or thoracic aortic insertion if necessary.
We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary artery bypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18F-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13%) was estimated in the segments with no 18F-FDG uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
The intra-aortic balloon pump (IABP) has been used for 23 years to treat cardiogenic shock from various causes. A retrospective review was conducted to evaluate the morbidity, mortality, and risk factors associated with insertion of this device. Over a recent 3-year period, 415 such pumps were inserted either by percutaneous (323) or cut-down (92) technique in 404 patients. Indications for placement included intraoperative pump failure (46%), cardiac instability before coronary artery bypass grafting (28%), perioperative support (13%), cardiac transplantation (7%), and cardiogenic shock (6%). Noncardiac vascular complications occurred in 67 patients, 55 per cent of whom required surgical correction. Operative procedures included femoral artery thrombectomy, bypass grafting, fasciotomy, and amputation. Major risk factors for vascular complications included diminished or absent femoral pulses on initial examination, being a woman, and obesity. In patients with known peripheral vascular disease, the risk of a vascular complication was 17.9 per cent when a surgical cut-down technique was used to insert the IABP, and 38.9 per cent when a percutaneous insertion was performed. The mortality doubled in those patients who had a vascular complication as compared to those who did not (34% vs 17%). A more liberal use of an open surgical technique in those patients with peripheral vascular disease, obesity, and who are women may help to reduce complications after the insertion of the intra-aortic balloon pump.
A significant number of patients with ischemic heart disease are not candidates for coronary artery bypass or percutaneous transluminal angioplasty and do not respond to medical management. This group includes those who have diffuse coronary artery disease, those with poor ventricular function, and those who have had poor results from previous surgery. Developing a method to directly revascularize the myocardium by creating channels through the ventricular wall has challenged many investigators. Early methods, including needle acupuncture, were successful in the acute phase, but long-term patency could not be achieved. Closure of the channels was due to fibrosis and scarring. Experiments in our laboratory demonstrated that myocardial channels, made with the CO2 laser, remained patent up to five years. Histopathologic examination of the channels showed minimal damage to the surrounding cells in the acute phase. Studies at intervals of two months to two years showed patent endothelialized channels, with no evidence of fibrosis. Channels created in the myocardium protected the ventricle against an ischemic event when the left anterior descending branch of the coronary artery was ligated. Clinical experience with direct myocardial revascularization by CO2 laser indicates it may be a viable method of treating those patients with ischemic heart disease who are not candidates for other forms of management. The treatment and early postoperative follow-up in one patient are described.
To assess the importance of contraction band necrosis (CBN) in patients with acute myocardial infarction (AMI) treated with selective intracoronary thrombolysis, CBN, coagulation necrosis, and infarct size (expressed as CBN + coagulation necrosis) were analyzed quantitatively in 16 autopsied hearts. Intracoronary thrombolysis was performed from 2 to 6 hr after the onset of AMI, and the time from the onset of AMI to death was 7 to 168 hr. Cineangiography revealed no evidence of good collateral circulation in any of the patients. The 16 patients were classified into three groups: six patients with successful thrombolysis (100% to 99% stenosis, group I), five patients with unsuccessful thrombolysis (100% to 100%, group II), and five patients with 99% stenosis before thrombolysis (group III). Among the three groups, there were no significant differences in the time from the onset of AMI to thrombolysis, the time from the onset of AMI to death, the cause of death, or the degree of collateral circulation. The percentage of the risk area involved by the infarct in group I (82 +/- 6%) was similar to that in group II (80 +/- 11%). Infarct size was not reduced in group I because collateral circulation was not good and because the degree of recanalization after thrombolysis was 1%. However, the percentage of the infarct area with CBN was significantly higher in group I (20 +/- 9%) then in group II (3 +/- 3%). This finding shows that diffuse CBN occurred after reperfusion in patients with AMI treated with thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Catheter insertion for intra-aortic balloon pumping (IABP) was successful in 91% of 332 candidates. Fifty-three patients (16.5%) had significant catheter-associated vascular complications, of which lower extremity ischemia with threatened limb loss was the most prevalent (70%). Thirty-six of these patients required an angioplastic repair or vascular grafting. Of the 36, 19 patients with ischemia who needed continued balloon support received femorofemoral (F-F) grafts to restore and maintain adequate limb perfusion. Wound infection occurred in six of the patients but there was no limb loss. F-F grafting is a simple procedure that requires little time and allows one to maintain IABP for prolonged periods without concern for critical obstruction to limb perfusion.
During a five-year period, 178 patients had the intraaortic balloon pump (IABP) inserted for circulatory support. The IABP was used most frequently as an adjunct for weaning patients from cardiopulmonary bypass. Seventy-seven of 103 patients (75%) were successfully weaned from cardiopulmonary bypass with the IABP, and 36 of them (35%) ultimately survived hospitalization. Other indications for the IABP included circulatory support before cardiac operation (16 patients), operative prophylaxis in high-rish patients (13), and postoperative hemodynamic support (23). Additionally, the IABP was placed in 23 patients who did not undergo cardiac operation. The incidence of IABP-related complications was significantly less when the IABP was inserted through the ascending aorta (4%) intraoperatively compared with the femoral or iliac artery (25%) (p less than 0.05). This was due primarily to vascular complications and groin wound infections that occurred with the femoral or iliac artery approach. IABP-related spinal cord paralysis developed in 3 patients (1.7%). We conclude that the IABP is an effective support device for treating patients with left ventricular failure particularly when weaning them from cardiopulmonary bypass. However, the risk of complications, including paraplegia, must be carefully weighed when use of the IABP is considered, especially in situations in which its efficacy is less clear.
We assessed the transmyocardial laser revascularization (TMLR) as sole therapy in patients with symptomatic coronary artery disease refractory to interventional or medical treatment.
Thirty-one patients were evaluated with positron emission tomography (PET), dobutamine echocardiography, 201Tl single-photon emission computed tomography (201Tl-SPECT), and multigated acquisition radionuclide ventriculography (MUGA). TMLR was performed in 21 patients who had demonstrable ischemia in viable myocardium. The mean Canadian Cardiovascular Society (CCS) angina class was 3.70 +/- 0.7 (4 patients with unstable angina). Untreated septal segments were used as controls. At 3 months, (n = 15 patients), the mean CCS angina class was to 2.43 +/- 0.9 (P < .05). On dobutamine echocardiography, the mean resting wall motion score index was improved by 16% in lased segments (P < .03 vs control), and mean LVEF at peak stress increased by 19% (P = NS vs baseline). On 201Tl-SPECT, perfusion of lased and nonlased segments did not change. On PET, the mean ratio of subendocardial to subepicardial perfusion (SEn/SEp) increased 14% over baseline (P < .001 vs control). At 6 months (n = 15 patients), the mean CCS angina class was 1.7 +/- 0.8 (P < .05). The mean resting wall motion score index was up by 13% in lased segments (P < .05 vs control). Resting LVEF was unchanged. Stress LVEF increased 21% (P = NS vs baseline). Myocardial perfusion remained unchanged by 201Tl-SPECT. On PET, 36% of the lased segments were better, and 25% were worse compared with baseline. The resting SEn/SEp by PET was up 21% (P < .001 vs control). All deaths (two perioperative and three late) occurred in patients with preoperative congestive heart failure. Two patients required repeat revascularization of new coronary lesions.
These results suggest that TMLR improves anginal status, relative endocardial perfusion, and cardiac function in patients who do not have preoperative congestive heart failure.
The increased incidence and prevalence of congestive heart failure place a high priority on novel treatment strategies. Left ventricular ejection fraction remains the single most valuable measurement providing both diagnostic and prognostic insights. The most systematic approach to heart failure involves an objective assessment of functional disability, to include exercise tests such as a 6-minute walk under standardized conditions. Left ventricular dysfunction incites a host of neurohumoral compensations that are of fundamental importance in the heart failure syndrome expression. Both vasoconstrictor and vasodilator neurohormones are stimulated and provide new therapeutic opportunities. The therapeutic approach to heart failure begins with a strong emphasis on prevention, patient education, and self-participation in therapy with respect to both its monitoring and adjustment. Diuretics remain a mainstay of therapy but, in the face of severe heart failure, may become ineffectual, requiring constant infusion of loop-active diuretics, combination diuretics, or diuretics in association with concomitant low-dose dopamine infusion. Vasodilator therapy has been an important advance: combination hydralazine and nitrate therapy was initially shown to be efficacious in improving survival, and more recently, angiotensin-converting enzyme (ACE) inhibitors, in the form of enalapril, have shown incremental benefit on survival over this combination. Interestingly, there is now evidence from both SOLVD and SAVE to demonstrate an unexpected and, as yet, unexplained reduction in the frequency of both unstable angina and myocardial infarction. Although, on balance, the weight of evidence concerning the long-term efficacy of inotropic agents has been disappointing, especially as it relates to their unfavorable effects on survival, recent information on vesnarinone, an agent with a complex and diversified mechanism of action, suggests that with appropriate doses, improved symptoms and survival are possible. A substantial amount of new information from randomized placebo-controlled trials attests to the symptomatic relief, hemodynamic improvement, and gain in exercise performance achieved by digoxin. A long-term survival study is ongoing to assess its effects on mortality. beta-Blockers, especially metoprolol, appear beneficial in some patients with heart failure, possibly related to their reduction in sympathetic nervous activity and restoration of beta-receptor population, with resultant improved contractile performance, enhanced myocardial relaxation, and overall increase in cardiac efficiency. Based on available evidence, the best contemporary approach to treatment involves the use of ACE inhibitors coupled with diuretic therapy, either continuous or intermittent, to relieve central or peripheral congestion. The addition of digoxin or a hydralazine nitrate combination is a logical next step, with commencement of low-dose beta-blocker a reasonable option.(ABSTRACT TRUNCATED AT 400 WORDS)
During the years 1988-1991 6319 patients underwent cardiac surgicalprocedures in Denmark. In 183 patients (2.9%) with left
ventricular failureintra-aortic balloon counterpulsation (IABP) was used. Four percent of theIABP were placed preoperatively,
86% intraoperatively and 10%postoperatively. Severe complications occurred in 16 patients (8.7%) andwere mainly vascular due
to limb ischemia. The incidence of complicationswas independent of the duration of balloon pumping. Sixty percent of thepatients
were weaned from IABP. The 30-day mortality rate was 54%. Duringthe observation period we found a gradual decrease in the
use of IABP aswell as a reduction in mortality.
We are investigating a new technique for myocardial revascularization in which an 800 W carbon dioxide laser is used to drill 1 mm diameter channels into a beating heart after left thoracotomy. Clotting occludes the channels on the subepicardium, and in the long-term setting, blood from the left ventricular cavity flows through these channels to perfuse the ischemic subendocardium. To test the efficacy of this technique in a preliminary clinical trial, we used it as sole therapy for 21 consecutive patients. All patients had hibernating myocardium, reduced coronary flow reserve, or both, had distal diffuse coronary artery disease, and had angina refractory to normal therapy. Eight patients were excluded from follow-up because of death (n=5), rerevascularization (n=2), or diaphragmatic paralysis resulting in postoperative respiratory incapacity (n=1). In the remaining 13 patients available for follow-up, the mean angina class (Canadian Cardiovascular Society) was 3.7 +/- 0.4 before operation and 1.8 +/- 0.6 12 months after operation (p < 0.01). Mean resting left ventricular ejection fraction was 48% +/- 10% before operation and 50% +/- 8% at 12-month follow-up. At 12 months, resting mean subendocardial/subepicardial perfusion ratio had increased by 20% +/- 9% in septal regions treated by laser but decreased by 2% +/- 5% in untreated regions (n=11, p <.001). These results suggest that revascularization by this laser technique positively affects subregional myocardial perfusion and may result in clinical benefits for patients with reversible myocardial ischemia. Studies to date have not demonstrated significant changes in global and regional ventricular contractile function.
A new technique, transmyocardial laser revascularization, provides direct perfusion of ischemic myocardium via laser-created transmural channels. From 1993 to 1995, we have treated 20 patients (mean age 61 years, four women and 16 men) with transmyocardial laser revascularization. Preoperatively, the average angina class was 3.7. The patients were screened before the operation by a technetium sestamibi perfusion scan to identify the location and extent of their reversible ischemia.
Operative exposure is gained via a left anterior thoracotomy. With the use of a 850-watt carbon dioxide laser, an average of 21 +/- 4 channels were created in 22 minutes with a total operative time of less than 2 hours.
The in-hospital mortality was two of 20 patients. Three additional patients died after discharge. After an accumulated 172 patient-months (mean follow-up 11 +/- 8 months, range 1 to 26 months), the mean angina class is I (p = 0.01). Postoperative sestamibi scans were obtained at 3, 6, and 12 months. Using the septum as a control and comparing the postoperative results with the preoperative baseline, we noted a significant improvement in perfusion particularly in the areas of reversible ischemia.
These early results indicate that transmyocardial laser revascularization is a simple operative technique that may improve myocardial perfusion and provide angina relief for patients in whom standard methods of revascularization is contraindicated.
The creation of transmyocardial channels from the epicardium to the left ventricular cavity with the use of a CO2 laser is a modern approach in the treatment of patients with chronic ischemic cardiac disease. The histological features of human myocardium at different times after transmyocardial laser therapy have not been previously described. We had the opportunity to examine hearts from patients who died without clinical evidence of a persistent therapeutic effect at 3, 16, and 150 days after transmyocardial laser revascularization (TMR) respectively.
We grossly localized the laser-created channels in unfixed and formalin-fixed tissue. Three ventricular levels were defined for cutting the hearts into four segments. Then, transmural blocks were excised and cut crosswise and lengthwise for histological investigation through the use of established staining methods. On day 3, laser-induced channels were filled with abundant granulocytes and thrombocytes, fibrinous network, and detritus and were surrounded by severe myocardial necrosis. Furthermore, the epicardial and endocardial portions were obstructed by fibrinous network and microclots. Granulocytes were mostly absent on day 16; in addition, the channels were filled with erythrocytes or fibrinous network. On day 150, we observed a string of cicatricial tissue admixed with a polymorphous blood-filled capillary network and small veins, which very rarely had a continuous wrinkled link to the left ventricular cavity.
We found different stages of wound healing in human nonresponder myocardium after TMR, resulting in scarred tissue that displayed capillary network and dilated venules without evidence of patent and endothelialized laser-created channels. Experimental studies are necessary to analyze the morphological basis for TMR-mediated effects in human responder myocardium.
Transmyocardial laser revascularization was used as the sole therapy for patients with ischemic heart disease not amenable to percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. This technique uses a carbon dioxide laser to create transmyocardial channels for direct perfusion of the ischemic heart.
Since 1992, 200 patients, at eight hospitals in the United States, have undergone transmyocardial laser revascularization. The patients have a combined 1560 months of follow-up for an average of 10 +/- 3 months per patient. Their age was 63 +/- 10 years and their ejection fraction was 47% +/- 12%. Eighty-two percent had at least one previous bypass graft operation and 38% had a prior angioplasty. Preoperatively, the patients underwent nuclear single photon emission computed tomography perfusion scans to identify the extent and severity of their ischemia. These scans were repeated at 3, 6, and 12 months. Angina class, admissions for angina, and medications were recorded.
The perioperative mortality was 9%. Angina class decreased significantly from before treatment to 3, 6, and 12 months (p < 0.001). Likewise, there was a significant decrease in the number of perfusion defects in the treated left ventricular free wall. Concomitantly, there was a significant decrease in the number of admissions for angina in the year after the procedure when compared with the year before treatment (2.5 vs 0.5 admissions per patient-year).
These combined results indicate that transmyocardial laser revascularization provides angina relief, decreases hospital admissions, and improves perfusion in patients with severe coronary artery disease.
Transmyocardial laser revascularization (TMR) is a new therapeutic principle for patients with coronary artery disease and no possibility of conventional revascularization with CABG or PTCA. The clinical value of the method is not known. Therefore we investigated all 46 patients treated with sole TMR in our center using clinical investigation, LV and coronary angiography, right heart catheterization, MIBI perfusion imaging and myocardial FDG-PET pre- and 6 months post TMR. 117 patients judged not suitable for conventional revascularization procedures were submitted for TMR. The indication for the procedure was reevaluated in every case. 52 patients (mean EF 41 +/- 16%) could be further treated by intensified anti-anginal medication, seven patients received bypass grafts, four patients had PTCA, three patients were listed for heart transplantation, and five patients had a combined CABG plus TMR. Only 46 (38% of the submitted patients, mean EF 55 +/- 15%) were accepted for sole TMR. CCS class of these patients was 3.3 +/- 0.4, mean age was 63.6 +/- 7.3 years, 70% were males. The postoperative mortality within 30 days was 5/46 (10.8%); 9/46 patients (19.5%) suffered from perioperative myocardial infarction. Other complications were ventricular fibrillation in two cases on the second postoperative day and a rupture of the spleen on the 14th postoperative day. 8/46 patients (17%) had wound infections. Survivors showed an improvement in their CCS class (1.9, 2.1, 1.9 after 3, 6 and 12 months, respectively, mean observation time 0.61 +/- 0.4 years). These patients were able to perform bicycle stress tests significantly longer (98 s +/- 9 pre versus 120 +/- 13 s post TMR, p = 0.01). Angiographic EF fell from 57.8% +/- 15% to 52.6% +/- 19% (p = 0.02) and the number of hypokinetic chords rose from 23.6 +/- 20.9% to 30.6 +/- 24.1% per patient (p = 0.008), predominantly in the inferior wall. Nuclear studies showed reduced myocardial perfusion and vitality after TMR. Four patients in the TMR group had reintervention (PTCA) because of progression of coronary sclerosis of native vessels. One patient had mitral valve replacement due to severe regurgitation. Kaplan-Meier analysis showed no significant difference in survival between the TMR and the medical group when stratified according to initial ejection fraction. Sudden death and congestive heart failure are the most important causes of mortality. Our data show that TMR improves symptoms and exercise performance of otherwise not treatable patients with diffuse coronary artery disease. Due to a lack of an improvement of cardiac perfusion, function or prognosis TMR should be used only in highly selected cases when conventional methods fail to improve patients symptoms.
Histologic examination of the human myocardium has been performed several days, weeks, and months after transmyocardial laser revascularization. We performed microscopic examinations 2 hours postoperatively. In addition to the patent channel (diameter, 1 mm) and a 1-to 2-mm rim of necrosis, a 1- to 3-mm zone of myofibrillary degeneration was found. This additional reversible injury immediately after transmyocardial laser revascularization could explain the higher mortality rate in patients with reduced left ventricular function.
Limb ischemia during intra-aortic balloon pumping: Indication for femorofemoral crossover graft
- J. Alpert
- V. Parsonnet
- R.J. Goldenkranz
- E.K. Bhaktan
- D.K. Brief
- B.J. Brenner
- I. Gielchinsky
- R.M. Abel
TMLR: Clinical results of patients transferred for transmyocardial laser revascularization
- G. Lutter
- M. Frey
- B. Saurbier
- E. Nitzsche
- J. Kobba
- J. Martin
- F. Beyersdorf