ELECTRO-MECHANICAL MAPPING OF THE LEFT VENTRICLE FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY.
A PLATFORM FOR INTRAMYOCARDIAL INJECTION OF GENE THERAPY TO PROMOTE MYOCARDIAL ANGIOGENESIS

David Fitchett, Michael Kutryk, Asim Cheema, Duncan Stewart
Terrence Donnelly Heart Centre, St Michael’s Hospital, University of Toronto
30, Bond St, Toronto, Ontario, CANADA M5B 1W8

INTRODUCTION

Left ventricular function in patients with ischemic heart disease can be impaired by either non-viable scar or hibernating / stunned viable ischemic myocardium. Distinction between ischemic viable and infarcted non-viable myocardium is important in assessing the potential value of coronary artery revascularisation. Myocardial viability can be assessed by scintigraphic perfusion imaging, stress echocardiography, or PET metabolic imaging. Electromechanical mapping simultaneously records both endocardial electrical activity and local left ventricular contraction throughout the cardiac cycle. Using normal electrical activity as an indicator of viable myocardium, hibernating or stunned myocardium can be identified by associated reduced local wall shortening.

The NOGA (Biosense: Cordis Webster) system is a cardiac catheter based method for electro-mechanical mapping of the left ventricle. The catheter tip is localized instantaneously in three-dimensional space throughout the cardiac cycle by an electromagnetic navigation system. With the catheter tip firmly touching the left ventricular endocardium both endocardial electrocardiograms and instantaneous movement of the catheter tip are recorded. Recordings are made from 60 to 120 points distributed throughout the left ventricle. Three-dimensional maps of electrical and mechanical activity are displayed which permit regions of electro-mechanical dissociation to be identified. Regions with severely reduced electrical and mechanical activity are likely to have little viable tissue. Whereas regions with relatively well preserved electrical activity yet reduced contractile function may contain severely ischemic yet viable myocardium.

Left ventricular regional wall motion by NOGA electromechanical mapping correlates well with findings from contrast left ventriculography [2]. Both experimental and human studies show that the NOGA system can distinguish infarcted from healthy myocardium [3]. Normal myocardium has a unipolar voltage of 17+ 5 mV, whereas in infarcted myocardium unipolar voltages of 7.0 + 3 mV are observed.  Chronically ischemic myocardium is associated with a severe reduction of local shortening (LS)(22.3+19 % vs 40+11%) whereas unipolar voltage (UV) is relatively well preserved (12.4+5mV vs 14.4+2mV) [4].  Subendocardial infarction is distinguished from transmural  infarction by better preservation of UV, despite very low LS. [5]

The NOGA electro-mechanical mapping system is a suitable platform for the intramyocardial delivery of growth factors and cell based therapy for both angiogenesis and heart failure [6]. Using a modified mapping catheter with an nitinol extendable 1.9 m long, 27g needle it is possible to direct intra-myocardial injections towards areas of viable myocardium and avoid injection into infarcted muscle. Care has to be taken to inject plasmid DNA through the needle at low flow rates to prevent shear damage to the DNA [7].

METHODS

The NOGA system has been used to complete a pilot safety study (SMART 2: St Michael’s Hospital Angiogenesis Revascularisation Trial 2) of intra-myocardial injection of plasmid DNA encoding the vascular endothelial growth factor (VEGF) in patients who are unsuitable for conventional methods of re-vascularisation (i.e. angioplasty or coronary bypass surgery). The area selected for injection of plasmid DNA is chosen primarily by the location of the maximal area of reversible ischemia identified by scintigraphic myocardial perfusion scanning. A 60 to 100 point NOGA map is recorded from the left ventricle. Within the pre-determined region the electro-mechanical map identifies severely ischemic myocardium that is the area targeted for 10 injections of plasmid DNA. Adequate stability of the catheter tip is determined prior to injection by measuring the variability of the loop trajectory of the catheter tip during consecutive cardiac cycles. Penetration of the myocardium by the needle is associated with the generation of several extra-systoles, and a visible stability of the catheter tip on fluoroscopy.

RESULTS

Evidence for the validity of the NOGA system for detecting viable ischemic myocardium will be presented.

Twelve patients were included in the SMART 2 study. In 11 patients an adequate map could be obtained which permitted localization of an ischemic area and the injection of plasmid DNA in an escalating doses from 70 to 1000 mg. The procedure was well tolerated in 11 of the twelve patients. One patient developed cardiac tamponade, which occurred after the mapping procedure and coincided with the removal of a temporary right ventricular transvenous pacemaker wire. This patient survived surgical pericardial drainage.

DISCUSSION

The SMART 2 study has shown the NOGA electromagnetic catheter navigation system is well suited for the localization of severely ischemic myocardium and the guidance of a catheter based needle injection system to areas most likely to benefit from the intra-myocardial injection of angiogenic growth factors. The time to obtain an adequate map is long (45-90 minutes) and there is a small but real risk of myocardial perforation during the procedure Currently no alternative method is available for both three dimensional catheter navigation and identification of viable and non-viable myocardium, although real-time MRI may be a method for the future.

Acknowledgements Work supported by The Ontario Heart and Stroke Foundation, Canadian Institute of Health Research, General Motors (Canada) and The Martin Family.

REFERENCES

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