(Circulation. 2000;102:1120.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Short- and Intermediate-Term Clinical Outcomes From Direct Myocardial Laser Revascularization Guided by Biosense Left Ventricular Electromechanical Mapping
From the Cardiovascular Research Institute (R.K., M.K.H., S.F.), Washington Hospital Center, Washington, DC; Beth Israel-Deaconess Hospital (D.S.B., R.J.L., D.W., D.J.C., R.E.K.), Boston, Mass; the Cardiovascular Research Foundation, Lenox Hill Hospital (J.W.M., M.B.L.), New York, NY; and Northwestern University Medical Center (R.C.H., R.O.B.), Chicago, Ill.
Correspondence to Ran Kornowski, MD, Cardiovascular Research Foundation, Washington Hospital Center, 110 Irving St NW, 4B-1, Washington, DC 20010. E-mail rxk3{at}mhg.edu
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Abstract |
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Background—Direct myocardial revascularization (DMR) has been examined as an alternative treatment for patients with chronic refractory myocardial ischemic syndromes who are not candidates for conventional coronary revascularization.
Methods and Results—We used left ventricular
electromagnetic guidance in 77 patients with chronic refractory angina
(56 men, mean age 61±11 years, ejection fraction 0.48±0.11) to
perform percutaneous DMR with an Ho:YAG laser at 2
J/pulse. Procedural success (laser channels placed in prespecified
target zones) was achieved in 76 of 77 patients with an average of
26±10 channels (range 11 to 50 channels). The rate of major
in-hospital cardiac adverse events was 2.6%, with no deaths or
emergency operations, 1 patient with postprocedural pericardiocentesis,
and 1 patient with minor embolic stroke. The rate of out-of-hospital
adverse cardiac events (up to 6 months) was 2.6%, with 1 patient with
myocardial infarction and 1 patient with stroke. Exercise duration
after DMR increased from 387±179 to 454±166 seconds at 1 month and to
479±161 seconds at 6 months (P=0.0001). The time to
onset of angina increased from 293±167 to 377±176 seconds at 1 month
and to 414±169 seconds at 6 months (P=0.0001).
Importantly, the time to ST-segment depression (
1 mm) also
increased from 327±178 to 400±172 seconds at 1 month and to 436±175
seconds at 6 months (P=0.001). Angina (Canadian
Cardiovascular Society classification) improved from
3.3±0.5 to 2.0±1.2 at 6 months (P<0.001). Nuclear
perfusion imaging studies with a dual-isotope technique, however,
showed no significant improvements at 1 or 6 months.
Conclusions—Percutaneous DMR guided by left ventricular mapping is feasible and safe and reveals improved angina and prolonged exercise duration for up to a 6-month follow-up.
Key Words: myocardium • lasers • ischemia • revascularization • angina
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Introduction |
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Previous surgical clinical trials in humans with carbon dioxide or Ho:YAG lasers for transmyocardial revascularization (TMR) have demonstrated a significant reduction in angina symptoms and improved quality-of-life (QOL) measures in patients with refractory coronary ischemia syndromes.1 2 3 The goal of catheter-based laser revascularization is to provide equivalent clinical efficiency without the need for a thoracotomy or general anesthesia.4 5 Furthermore, the catheter-based approach may reduce procedural complications and lower hospital expenses.
The Biosense direct myocardial revascularization (DMR) Ho:YAG laser system was designed to produce relatively small (0.5- to 1-mm diameter over a 3- to 5-mm depth) myocardial channels with collateral injury zones comparable in total volume to those of surgical laser channels.6 Moreover, precise navigational control of the catheter tip, with the use of magnetic field emitters and location sensors with minimal use of x-ray fluoroscopy, allows laser channel placement in prespecified ischemic endocardial target regions. This online guidance system may increase both the safety and efficacy of catheter-based laser DMR procedures. This strategy is a less-invasive approach for TMR compared with the surgical technique; safety and feasibility have been assessed and reported previously in experimental animal models.6
The purpose of the present study was to demonstrate for the first time the safety and feasibility of the Biosense DMR system as a therapeutic strategy designed to reduce angina and to improve ischemic response in patients with chronic refractory ischemic heart disease.
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Methods |
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Patient Population
Patients were candidates for the safety and feasibility phase of the Biosense DMR procedure if they (1) had symptomatic coronary artery disease with chronic refractory angina defined as Canadian Cardiovascular Society (CCS) class III to IV angina despite best tolerated pharmacological therapy (ie, long- or short-acting nitrates, ß-adrenergic–blocking agents, or calcium antagonists at maximal tolerable doses), (2) were poor candidates for percutaneous angioplasty, and (3) were poor candidates for surgical revascularization procedures. These criteria were determined by at least 2 physicians in each of the tertiary referral centers that participated in the study, in addition to a similar definition made by the referral cardiologist. Major exclusion criteria included severe left ventricular (LV) dysfunction (ejection fraction [EF] <0.30), recent (within 1 month) myocardial infarction (MI), recent (<4 months) angioplasty, chronic atrial fibrillation, and major (life-threatening) comorbidity. Informed consent had been obtained for all patients who were potential trial candidates before the procedure. All antianginal medications (long- or short-acting nitrates, ß-adrenergic–blocking agents, and calcium antagonists) were continued at their long-term prescribed dosages throughout the course of the study. Medical history, pertinent physical examination, laboratory studies (CBC with platelet count, cardiac enzymes [CK-MB], and blood chemistry) and 12-lead ECG were obtained the day before the DMR procedure. On the day before the DMR procedure, each patient underwent a transthoracic echocardiogram, a standard treadmill exercise test (modified Bruce/Beth-Israel protocol), and radionuclide stress dual-isotope perfusion studies with SPECT techniques. All patients had a positive exercise tolerance test defined as chest pain symptoms and ST-T changes that developed during exercise or the recovery period and evidence of reversible perfusion defect during the SPECT study.
Study End Points
The primary end point of the present study was the absence
of in-hospital major adverse cardiac events (MACE) defined as death, MI
(Q and non–Q wave defined as CK-MB ratio >8 normal value), LV
perforation (with and without cardiac tamponade), systemic embolization
(including cerebrovascular events), CABG (for procedure-related
complications), and PTCA (for procedure-related complications) and the
incidence of MACE up to 6 months defined as a combination of death,
recurrent MI (Q and non–Q wave), and ischemia-driven
revascularization procedures. The end points for
this trial were adjudicated by an outside clinical event committee.
Secondary end points included (1) procedural success defined as device
success without intraprocedural complications (MACE), (2) change
in exercise time at 30 and 180 days, (3) change in radionuclide
perfusion studies at the treatment sites at 30 and 180 days, (4)
improvement in angina and health status according to the Seattle
anginal questionnaire (quantitative instruments) and change in CCS
angina class compared with baseline at 14, 90, and 180 days, and (5)
change in repeat LV electromechanical mapping at 6 months.
Myocardial Perfusion Imaging
At baseline and 1 and 6 months after DMR, all patients underwent
SPECT myocardial perfusion imaging with a dual-isotope protocol with 3
mCi 201Tl for rest and 25 mCi
99mTc-sestamibi for adenosine-stress
imaging according to previously published methodology.7
Sestamibi was administered at 3 minutes of the 6-minute
adenosine infusion (140 µg ·
kg-1 · min-1).
Stress imaging was performed beginning 60 minutes after
99mTc-sestamibi injection. These data were
submitted to the central core laboratory for blinded uniform
processing, interpretation, and comparative analysis. A
20-segment semiquantitative visual analysis was used as well as
an automated quantitative analysis. The following score was
used: 0, normal; 1, mildly reduced uptake; 2, moderately reduced
uptake; 3, severely reduced uptake; and 4, no uptake. The summed scores
of rest, rest-redistribution, and stress images were determined at 1-
and 6-month follow-up and compared with baseline values.
LV Mapping and DMR
The LV electromechanical mapping system and procedure have been
previously described in detail.7 8 Heparin was
administered (70 U/kg) and supplemented as needed to maintain an ACT of
200 to 250 seconds. After acquisition of the LV map, all patients were
advanced to the laser DMR phase of the study. Treatment zones for this
study were predefined using both the SPECT imaging and the
diagnostic LV mapping data according to the following
criteria: (1) voltage amplitudes of >10 mV and local endocardial
shortening (LS) of <6%, signifying severe myocardial ischemia
at rest,9 (2) voltage amplitudes of 7 to 10 mV with
reference regions of >10 mV regardless of LS values,7 8
and (3) laser channels not placed in zones with voltage amplitudes of
6 mV that likely represent infarct tissue,7 8 or
in areas with myocardial thickness of <9 mm as detected by
echocardiography (4) in case of voltage amplitudes
of >10 mV and LS values of >10%, the definition of target zones for
DMR was made exclusively based on the SPECT definition.
At the conclusion of LV mapping, an 8F laser catheter was introduced
and advanced to the LV. The laser source was a pulsed Ho:YAG laser
(Sharplan 2040; Ho:YAG Laser Systems). Laser channels were
created using a tip-deflecting mapping and Ho:YAG laser catheter
integrated with a 300-µm fiber (LaserStar;
Biosense-Webster). After a transmission test, the DMR catheter was
inserted through the femoral artery sheath, and the DMR procedure was
initiated. A single laser pulse (2 J/pulse) was fired as close
as possible to perpendicular to the endocardial surface with the
catheter tip icon used to verify the location and orientation of the
tip in relation to the mapped endocardium. Between 10 and 25 laser
pulses were fired within the confines of the treatment zone with
5 mm between each laser pulse. The software provides precise
visual annotation of the location in 3 dimensions for each laser pulse.
Care was taken to avoid the mitral valve apparatus, the LV
apex, and regions of myocardium with known previous
infarction or thinning (see earlier). The system allowed the laser to
fire only if a QRS peak was detected to which the laser was triggered
and the stability of the cycle length and catheter location were
verified. At the conclusion of the laser DMR procedure, all patients
were monitored (ECG, arterial and right heart pressures) in
the catheterization laboratory for 15 minutes. At the
end of the procedure, patients were transferred to an intermediate care
facility with continuous ECG monitoring overnight. Blood samples for
CK-MB were serially acquired from all patients every 8 hours for 24
hours after the procedure. CK-MB elevation has been defined as
"minor" (1 to 3 times normal), "intermediate" (3 to 8 times
normal), and "major" (>8 times normal). In addition, serial
12-lead ECGs were acquired from all patients every 8 hours for 24 hours
after the procedure. Transthoracic echocardiograms were
obtained within 1 hour of the procedure and the next day before
hospital discharge.
Electromechanical Mapping Data
Repeat electromechanical mapping was performed before and at 6
months after laser DMR in most patients. LV maps were projected
into 16-segment models, and unipolar voltage amplitudes (UpVs) and LS
data were submitted to a central core laboratory for interpretation and
matched analysis.7 8 9 Segments (n=864) were
distinguished by the number of annotated laser channels per mapped
segment (none, 1 to 5, 6 to 10, >10 channels per segment) to examine
the presence of a regional treatment effect.
Follow-Up (Postdischarge)
Patient follow-up included evaluations at 2 weeks (QOL
assessment), 1 month (exercise test,
echocardiography, and dual-isotope SPECT), 3 months
(QOL assessment), and 6 months (exercise test, dual-isotope SPECT, and
repeated electromechanical mapping). All follow-up end point
assessments were performed at the specific times indicated unless the
patient required hospitalization. All follow-up assessments (exercise
test, echocardiography, SPECT, LV mapping, and QOL
assessment) were performed at independent core laboratories, and data
were transferred to a coordinating center
(Cardiovascular Data Analysis Center, Boston,
Mass).
Statistical Analysis
All data are presented as mean±1 SD. Nominal data
(pre-DMR versus post-DMR) were compared by paired t test
analysis. Fractional values were compared by
2 analysis. Changes in
electromechanical mapping data were calculated and compared by trend
analysis. P value of <0.05 was considered
statistically significant.
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Results |
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Patients
Seventy-seven patients who fulfilled protocol inclusion criteria were enrolled from the 3 institutions and were entered into the study. Clinical demographics are presented in the Table
. The majority of patients underwent CABG or
PTCA in the distant past. The average EF was 0.48±0.12. The use of
antianginal medications is outlined in the Table. With only a
few exceptions, all study medications were kept constant throughout the
course of the study. The mean heart rate at rest was 64.6±10.8 bpm
(range 45 to 89 bpm), with 78% of patients having a resting heart rate
of <70 bpm. The mean systolic and diastolic blood
pressures were 130.7±23.2 and 75.3±9.3 2 mm Hg,
respectively.
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Procedural Details
In all cases, full electromechanical maps were obtained without
complications. The overall number of mapping points was 78±21 (range
40 to 134), and the LV mapping time before DMR was 26±9 minutes (range
13 to 50 minutes). After electromechanical map acquisition and online
interpretation, all patients were advanced to the DMR treatment phase
of the study. Each patient received an average of 26±10 (range 11 to
50) laser pulses in an average of 1.6±0.5 treatment zones (defined as
either anterior, lateral, or inferoposterior). Device success was
achieved in 76 of 77 patients. In 1 patient, a sufficiently stable
endomyocardial position could not be established to
permit safe laser firing due to small ventricular cavity
size, marked hypercontractility, and persistent
multiple ventricular premature beats; the procedure was
aborted and recorded as a technical failure. The average DMR
procedure time was 29±13 minutes (range 9 to 78 minutes), and the
overall procedure time (mapping and laser) was 55±12 minutes (range 26
to 129 minutes). Treatment zones were anterior (n=31), lateral (n=32),
inferior (n=25), and posterolateral (n=24). Two
representative cases of percutaneous
DMR with use of the Biosense electromechanical
navigational system in the anterior and inferior walls are
shown in Figures 1A and 1B,
respectively.
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In-Hospital Clinical Events
Procedural success, defined as device success without the
occurrence of MACE through hospital discharge, occurred in 76 of 77
patients (98.7%). The 1 procedural failure was described. There were 2
in-hospital complications; 1 patient had postprocedural stroke
manifested by left-sided diplopia and ptosis with diagnosis of third
cranial nerve palsy. The second complication involved a patient who
underwent angioplasty to treat a total occlusion of the left posterior
descending branch of the left circumflex artery immediately before the
DMR procedure. After a series of guidewires were used without success
to cross the lesion, the patient was immediately enrolled into the DMR
study. A routine postprocedural echocardiogram revealed a large (200 to
300 mL) pericardial effusion that was drained with a subxiphoid
catheter to prevent hemodynamic consequences. This
procedure was performed without difficulty, with the return of normal
hemodynamic and echocardiographic
findings. The patient was observed overnight in the coronary
care unit and had no further complications. It is unclear whether the
perforation occurred as a result of the angioplasty attempt with stiff
guidewires or of the DMR procedure.
There were no deaths, Q-wave or non–Q-wave MIs, or emergency angioplasty or surgical procedures. Importantly, no patient experienced clinical heart failure after DMR. Three patients (4.2%) sustained significant CK-MB enzyme elevations (>3 and <8 CK-MB ratio). Eighteen patients (22.2%) sustained CK-MB elevation of >1 but <3 times normal values. No permanent ECG changes have been noted in any patient. Postprocedural echocardiography revealed no LV dysfunction or valve damage (see later). There have been no significant vascular complications (transfusion or surgical repair) in any patient. Generally, patients were discharged the next day, and none could identify specific negative effects or symptoms associated with the DMR procedure.
Follow-Up Clinical Events
There were no deaths or Q-wave MIs from the time of DMR to the
6-month follow-up. There were 4 post-DMR
revascularization procedures (angioplasty in 2
patients, bypass surgery and surgical TMR in 1 patient, and bypass
surgery alone in an additional patient) due to progressive
coronary disease and continued or worsening symptoms. One
patient sustained a non–Q-wave MI between hospital discharge and 1
month, and an additional patient sustained a stroke. One patient was
diagnosed as having colon cancer and underwent abdominal surgery.
Echocardiographic Data
Transthoracic echocardiography was
performed within 24 hours before DMR, within 24 hours after the
procedure, and again at 1 month. There was no change in the average
measured LVEF after DMR or during follow-up (0.48±0.12 postprocedure
and 0.46±0.11 at 1 month versus 0.48±0.11 at baseline,
P=NS for both comparisons). Interestingly, the degree of
mitral regurgitation (assessed on a scale of 0 to +4)
did not change acutely after DMR (1.9±1.2 postprocedure versus
2.0±1.1 at baseline, P=NS), but at 1 month, an overall
decrease was noticed in the degree of mitral
regurgitation compared with before DMR (1.7±1.0 versus
2.0±1.1, P=0.038). Diastolic function as
detected by mitral inflow E/A ratio showed a significant improvement at
1 month (1.35±0.61) compared with E/A wave ratio value before DMR
(1.23±0.50, P=0.014).
Exercise Test Data
Significant prolongation in exercise duration was noted throughout
the study among treated patients. Exercise duration after DMR increased
from 387±179 to 454±166 seconds at 1 month and 479±161 seconds at 6
months (P=0.001 and P=0.0001 versus baseline,
respectively) (Figure 2). By paired
analysis, there was a 49±111- and 78±107-second exercise
prolongation at 1 month (65 patients) and 6 months (56 patients) after
the DMR procedure (P<0.001 for both comparisons versus
baseline). The time to angina symptom onset during exercise after DMR
increased from 293±167 to 377±176 seconds at 1 month and 414±169
seconds at 6 months (P=0.0001 for versus baseline).
Importantly, the time to ST-segment depression (1 mm) during
exercise was also increased from 327±178 to 400±172 seconds at 1
month and 436±175 seconds at 6 months (P=0.001 for both
comparisons versus baseline).
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Angina Assessment
Angina class (CCS) improved from 3.3±0.5 to 2.3±1.1, 2.1±1.1,
and 2.0±1.1 at 2 weeks and 3 and 6 months, respectively
(P<0.001 for each comparison versus baseline, Figure 3). Of the patients, 75% and 79%
experienced sustained symptomatic improvement of 1 CCS
class at 3 and 6 months, respectively, whereas 33% and 43% of the
patients experienced sustained symptomatic improvement of
2 CCS classes at 3 and 6 months, respectively. Angina stability score
showed a sustained improvement from a value of 35.8±26.2 at baseline
to 70.0±25.4, 66.7±28.5, and 71.8±28.8 at 2 weeks and 3 and 6
months, respectively (P<0.0001).
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Nuclear Imaging
The visual summed stress scores data failed to show a difference
between baseline and the 30-day study (20.0±11.5 versus 19.1±10.7,
P=NS) or the 6-month SPECT study (19.2 versus 18.8,
P=NS) for 65 patients. Similar findings were noted for the
summed rest and rest 4-hour redistribution scores. A blinded visual
side-by-side comparison of the perfusion data also failed to reveal a
treatment effect. Quantitative analysis confirmed the lack of a
demonstrated effect on myocardial perfusion by radioisotope imaging
technique. When regional perfusion data were correlated to the
laser-treated regions, no effect on perfusion was noted with DMR
treatment. Thus, overall nuclear perfusion studies with a
dual-isotope technique did not show significant improvements in rest,
stress, or redistribution imaging scores at 1- and 6-month follow-up
after DMR.
Electromechanical Mapping
Segments (n=864) were distinguished by the number of
annotated laser channels per mapped segment (none, 1 to 5, 6 to 10,
>10 channels per segment; n=477, 267, 87, and 33 segments,
respectively). On average, 25±12% of the endocardial surface area was
treated with a mean channel density of 1.0±0.4
channel/cm2 within the treatment zone. The
overall and regional unipolar voltage showed slight but significant
(P<0.05) reduction (by 
1 mV) in voltage amplitudes
observed at 6 months compared with baseline without an apparent effect
of DMR or the number of laser channels placed on this finding (Figure 4). By contrast, LS improved from
baseline to 6 months in DMR-treated segments but not in segments
without treatment. Moreover, the increase in LS was related to the
channel density (8.7%, 25.5%, and 40.8% increase in LS by 6 months
in zones with 1 to 5, 6 to 10, and >10 channels per segment,
respectively, versus 2% change in nontreated segments; Figure 4, P<0.001).
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Discussion |
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In the present study, we examined the use of a novel electromagnetic field–based LV navigational system integrated with an Ho:YAG laser catheter specifically designed for the DMR procedure. The results of this study shows for the first time that Biosense-guided DMR (1) is technically feasible in the vast majority of patients with an acceptable safety profile, (2) provides enhanced diagnostic and localization information that facilitates precise placement of laser channels, (3) results in few complications, and (4) may provide sustained clinical benefit, including improved angina and prolonged exercise duration, that extends up to 6-month follow-up. Although nuclear perfusion studies failed to show significant improvements in perfusion assessments, repeat LV mapping documented significant improvements in mechanical activity in laser-treated areas that seemed to correlate well with the number of laser channels per segment.
Rationale for DMR
DMR is a generic term that is meant to embrace all forms of
treatment that involve intramyocardial approaches to improve anginal
symptoms, not those that occur via the epicardial coronary
tree. Extensive surgical experiences with transmural intraoperative
laser DMR have indicated significant reduction in angina severity,
improved exercise tolerance, and improved QOL but no evidence of
improved myocardial perfusion in patients who sustain refractory
coronary ischemic syndromes.1 2 3 The
likely mechanism of DMR action has not been fully elucidated and may
result from local microvascular angiogenic response, local nerve damage
that causes an anesthetic effect, or both.10 11 The goal
of catheter-based DMR is to create nontransmural
endomyocardial channels that are smaller than but
comparable in tissue effect to the surgical DMR without the need for
surgery or general anesthesia. In addition, it enables
access to areas not approachable with surgical DMR (eg, the
ventricular septum and the posterior wall) and provides
opportunities for multiple treatment sessions with a lesser invasive
approach. Furthermore, in theory, the catheter-based alternative to
surgery may be associated with lower procedural morbidity and mortality
rates. At the present, percutaneous DMR experiences
appear promising, with preliminary results from catheter-based DMR
clinical trials that report clinical efficacy and safety comparable to
those of the surgical procedure.12
LV Mapping to Guide DMR
There are several unique features of the electromagnetic
field–based system that may be advantageous to optimize the safety and
efficacy of DMR procedures. The navigation and mapping rely solely on
low-energy electromagnetic fields generated for real-time 3-dimensional
reconstruction of the LV endocardial surface with only minimal or no
need for fluoroscopy or contrast administration. Due to the ability to
collect the endocardial voltage amplitudes, the status of myocardial
viability (presence of normal or reduced voltage amplitudes) can be
determined.13 This enables the identification of potential
ischemic target zones that may benefit from laser DMR
treatment. The mechanical map (end-systolic and
end-diastolic volumes, EF, and LS) provides global and
regional contractility data. This property can
eventually be used for accurate anatomic identification of the "area
at risk," to be used to direct treatment to the proper
ischemic site and to avoid the treatment of nonviable infarct
issue.7 8 9
We attempted to address the following issues regarding LV-guided DMR: (1) safety and feasibility of LV mapping and subsequent "guided" DMR in patients with coronary artery disease and (2) assessment of the efficacy of laser DMR through independent core laboratory evaluation of symptomatic improvement, exercise test changes, and perfusion assessment after DMR. The results of the study clearly demonstrate both feasibility and safety; the procedure was successfully completed in all except 1 patient. The frequency of major complications in this study was low (2.6%); only 1 patient had myocardial perforation, and an additional patient had a small cerebrovascular embolic event. Echocardiography before and after the laser DMR procedure was further confirmatory through the exclusion of LV function deterioration, new aortic or mitral valve abnormalities, or pericardial effusion except for the 1 patient we described. The practical use of the Biosense system to generate electromechanical maps was also confirmed in the present study. Data obtained from the ventricular maps were useful in the identification of target ischemic regions for laser DMR procedure and agreed with antecedent interpretation of diagnostic radionuclide scans. Moreover, with voltage amplitudes and mechanical activity data, the avoidance of laser channel placement could be achieved in (1) the mitral valve area (eg, low-voltage amplitudes in the posterior ventricular area) and (2) areas that sustained prior myocardial infection (eg, low-voltage amplitudes and reduced mechanical activity).13
Study Limitations
The potential advantage of electromechanical mapping as a platform
modality for DMR must be established and compared in the future with
other systems that use either x-ray fluoroscopy or
echocardiography for guidance. Despite the observed
promising efficacy end points, the present study was not designed
to establish the efficacy of the laser DMR procedure. A large-scale
blinded randomized clinical trial is under way to establish the
definitive therapeutic value of laser DMR. Although the potential
mechanisms that may be responsible for a beneficial clinical effect are
being elucidated in experimental animal models, our data provide little
insight into the potential mechanistic effects of laser DMR in patients
with myocardial ischemia. Although far from conclusive, the
improved time to ST-segment changes during exercise and the improved LS
in the treated zones are suggestive of a positive
physiological effect, as opposed to a simple
placebo effect. Finally, there remain many unknowns about DMR, which
should lead to further clinical investigation; examples include the
importance of channel size (depth and diameter) and channel spacing as
the need for precise endocardial localization with online guidance
systems, the ideal treatment "substrate" (ie, ischemic,
border zone, or normal myocardium that supplies
collaterals), and the durability of clinical outcomes. Further
randomized controlled clinical trials are needed to address these
important issues.
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Acknowledgments |
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This work was supported by Biosense-Webster, a Johnson and Johnson Company (Diamond-Bar, Calif).
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Footnotes |
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Drs Kornowski, Baim, and Leon are consultants to Biosense-Weber, which makes the revascularization system discussed in the article. Drs Kornowski and Baim also received research grants to their institutions from the company.
Received February 24, 2000; revision received April 3, 2000; accepted April 13, 2000.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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1. Burkhoff D, Schmidt S, Schulman SP, et al. Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial: ATLANTIC investigators: Angina Treatments—Lasers and Normal Therapies in Comparison. Lancet. 1999;354:885–890.[Medline] [Order article via Infotrieve]
2.
Allen KB, Dowling RD, Fudge TL, et al. Comparison of
transmyocardial revascularization with medical
therapy in patients with refractory angina. N Engl J
Med. 1999;341:1029–1036.
3.
Frazier OH, March RJ, Horvath KA. Transmyocardial
revascularization with a carbon dioxide laser in
patients with end-stage coronary artery disease. N
Engl J Med. 1999;341:1021–1028.
4. Kornowski R, Bhargava B, Leon MB. Percutaneous transmyocardial laser revascularization: an overview. Cathet Cardiovasc Intervent. 1999;47:354–359.[Medline] [Order article via Infotrieve]
5. Kornowski R, Hong MK, Leon MB. Current perspectives on direct myocardial revascularization. Am J Cardiol. 1998;81:44E–48E.[Medline] [Order article via Infotrieve]
6. Kornowski R, Hong MK, Haudenschild CC, et al. Feasibility and safety of percutaneous laser revascularization using the Biosense system in porcine hearts. Coron Artery Dis. 1998;9:535–540.[Medline] [Order article via Infotrieve]
7.
Kornowski R, Hong MK, Leon MB. Comparison between left
ventricular electromechanical mapping and radionuclide
perfusion imaging for detection of myocardial viability.
Circulation. 1998;98:1837–1841.
8.
Kornowski R, Hong MK, Gepstein L, et al. Preliminary
animal and clinical experiences using an electromechanical endocardial
mapping procedure to distinguish infarcted from healthy
myocardium. Circulation. 1998;98:1116–1124.
9. Fuchs S, Kornowski R, Shiran A, et al. Electromechanical characterization of myocardial hibernation in a pig model. Coron Artery Dis. 1999;10:195–198.[Medline] [Order article via Infotrieve]
10.
Yamamoto N, Kohmoto T, Gu A, et al. Angiogenesis is
enhanced in ischemic canine myocardium by
transmyocardial laser revascularization.
J Am Coll Cardiol. 1998;31:1426–1433.
11.
Al-Sheikh T, Allen KB, Straka SP, et al. Cardiac
sympathetic denervation after transmyocardial laser
revascularization. Circulation. 1999;100:135–140.
12.
Lauer B, Junghans U, Stahl F, et al. Catheter-based
percutaneous myocardial laser
revascularization in patients with end-stage
coronary artery disease. J Am Coll Cardiol. 1999;34:1663–1670.
13. Kornowski R, Leon MB. Left ventricular electromechanical mapping: current understanding and diagnostic potential. Cathet Cardiovasc Intervent. 1999;48:421–429.[Medline] [Order article via Infotrieve]
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 C. R. Bridges, K. A. Horvath, W. C. Nugent, D. M. Shahian, C. K. Haan, R. J. Shemin, K. B. Allen, and F. H. Edwards The Society of Thoracic Surgeons practice guideline series: transmyocardial laser revascularization Ann. Thorac. Surg., April 1, 2004; 77(4): 1494 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ruel, R. A. Kelly, and F. W. Sellke Therapeutic Angiogenesis, Transmyocardial Laser Revascularization, and Cell Therapy Card. Surg. Adult, January 1, 2003; 2(2003): 715 - 750. [Full Text]
|
|
|
|
|
|
R. Kornowski Left ventricular electromechanical mapping for determination of myocardial function and viability J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1075 - 1078. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lessick, G. Hayam, A. Zaretsky, S. A. Reisner, Y. Schwartz, and S. A. Ben-Haim Evaluation of inotropic changes in ventricular function by NOGA mapping: comparison with echocardiography J Appl Physiol, August 1, 2002; 93(2): 418 - 426. [Abstract] [Full Text] [PDF]
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|
|
|
|
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G. W. Stone, P. S. Teirstein, R. Rubenstein, D. Schmidt, P. L. Whitlow, E. J. Kosinski, G. Mishkel, and J. A. Power A prospective, multicenter, randomized trial of percutaneous transmyocardial laser revascularization in patients with nonrecanalizable chronic total occlusions J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1581 - 1587. [Abstract] [Full Text] [PDF]
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|
 |
|
 C.V Patil, E Nikolsky, M Boulos, E Grenadier, and R Beyar Multivessel coronary artery disease: current revascularization strategies Eur. Heart J., July 2, 2001; 22(14): 1183 - 1197. [PDF]
|
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|
|
 |
|
 P. R. Vale, D. W. Losordo, C. E. Milliken, M. C. McDonald, L. M. Gravelin, C. M. Curry, D. D. Esakof, M. Maysky, J. F. Symes, and J. M. Isner Randomized, Single-Blind, Placebo-Controlled Pilot Study of Catheter-Based Myocardial Gene Transfer for Therapeutic Angiogenesis Using Left Ventricular Electromechanical Mapping in Patients With Chronic Myocardial Ischemia Circulation, May 1, 2001; 103(17): 2138 - 2143. [Abstract] [Full Text] [PDF]
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