Ignite Creation Date:
2024-05-06 @ 1:17 PM
Last Modification Date:
2024-10-26 @ 1:12 PM
Study NCT ID:
NCT03985241
Status:
COMPLETED
Last Update Posted:
2019-12-19
First Post:
2019-06-05
Brief Title:
Functional Assessment of Myocardial Ischemia by Intracoronary Electrocardiogram
Sponsor:
Insel Gruppe AG University Hospital Bern
Organization:
Insel Gruppe AG University Hospital Bern
Study Overview
Official Title:
Functional Assessment of Myocardial Ischemia by Intracoronary Electrocardiogram
Status:
COMPLETED
Status Verified Date:
2019-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FFRicECG
Brief Summary:
In patients with chronic stable coronary artery disease CAD percutaneous coronary intervention PCI targets hemodynamically significant coronary lesions ie those thought to cause inducible ischemia The hemodynamic severity of a coronary stenosis increases with its tightness and with the myocardial mass of viable myocardium downstream of the stenosis
Compared to the traditional anatomic angiographic approach assessment of functional relevance by fractional flow reserve FFR during coronary angiography has been suggested to improve patient outcomes Fractional flow reserve FFR is based on determination of the coronary perfusion pressure downstream of a stenosis during pharmacologic hyperemia However FFR relies on oversimplified physiologic concepts which limits its usefulness in defining a true ischemic threshold Furthermore visual angiographic assessment continues to dominate the treatment decisions for intermediate coronary lesions
Conversely the intracoronary ECG icECG provides an inexpensive sensitive and direct measure of myocardial ischemia The icECG is easily acquired by attaching a reusable alligator clamp to a conventional angioplasty guidewire at one tenth the price of a pressure sensor guidewire The coronary guide wire positioned downstream of a coronary stenosis then acts as the exploring electrode During pharmacologic stress the icECG can provide direct evidence for regional myocardial ischemia to define the ischemic threshold in different types of coronary artery disease
Compared to the traditional anatomic angiographic approach assessment of functional relevance by fractional flow reserve FFR during coronary angiography has been suggested to improve patient outcomes Fractional flow reserve FFR is based on determination of the coronary perfusion pressure downstream of a stenosis during pharmacologic hyperemia However FFR relies on oversimplified physiologic concepts which limits its usefulness in defining a true ischemic threshold Furthermore visual angiographic assessment continues to dominate the treatment decisions for intermediate coronary lesions
Conversely the intracoronary ECG icECG provides an inexpensive sensitive and direct measure of myocardial ischemia The icECG is easily acquired by attaching a reusable alligator clamp to a conventional angioplasty guidewire at one tenth the price of a pressure sensor guidewire The coronary guide wire positioned downstream of a coronary stenosis then acts as the exploring electrode During pharmacologic stress the icECG can provide direct evidence for regional myocardial ischemia to define the ischemic threshold in different types of coronary artery disease
Detailed Description:
INVASIVE PRESSURE-DERIVED INDICES OF STENOSIS SEVERITY
In the setting of stable coronary artery disease CAD PCI or coronary artery bypass grafting CABG targets coronary lesions causing inducible myocardial ischemia With the advancement of technology the development of a coronary pressure guide wire enabled to reliably measure coronary perfusion pressure downstream of a stenosis and therefore trans-stenotic pressure gradients On the basis of comparisons to noninvasive stress tests the concept of fractional flow reserve FFR was introduced FFR determines the ratio of mean distal coronary pressure and mean aortic pressure the effective coronary perfusion pressure during pharmacologic hyperemia A FFR value of near 1 is then equivalent to a totally normal coronary artery whereas a cutoff of 075-080 is commonly used to determine that PCI is warranted
With FFR pharmacologic hyperemia is mandatory to induce minimal and constant myocardial resistance which is the basis to directly relate coronary pressure and flowIn contrast the recently introduced concept of the instantaneous wave-free ratio iFR claims to obviate the need for administration of pharmacologic stress Instead coronary pressure is analyzed at rest and during part of coronary diastole when myocardial resistance is thought to be naturally constant and minimal the so called wave-free period
LIMITATIONS OF PRESSURE-DERIVED INDICES OF STENOSIS SEVERITY IN DEFINING THE ISCHEMIC THRESHOLD
A major limitation of pressure-derived indices of stenosis severity is related to the assumption of oversimplified physiologic concepts Clinically the diagnostic accuracy of FFR is restricted in three scenarios Firstly the pressure gradient evaluated by FFR is critically dependent on the magnitude of resistance offered by the microcirculation With microvascular dysfunction microvascular resistance remains inadequately high during pharmacologic hyperemia meaning that the pressure gradient across the stenosis does not reflect the epicardial stenosis severity overestimation of FFR
Secondly with a focal stenosis but well-preserved microvascular function and minimal diffuse atherosclerosis hyperemic coronary flow although reduced may still be above the ischemic threshold although the pressure gradient suggests otherwise Thirdly with severe diffuse coronary atherosclerosis coronary flow may be reduced below the ischemic threshold but with only an insignificant fall in the hyperemic pressure gradient FFR In summary although FFR claims otherwise the ischemic threshold set by FFR is unreliable in a significant proportion of pathophysiological and clinical scenarios
DIRECT ASSESSMENT OF REVERSIBLE MYOCARDIAL ISCHEMIA BY INTRACORONARY ELECTROCARDIOGRAM
The electrocardiogram ECG is an indispensable tool in the diagnosis of myocardial ischemia The commonly used surface ECG is however limited especially in detecting short-lasting or minor myocardial ischemia Furthermore ischemia in the territory of the left circumflex coronary artery is often undetected Conversely due to its close vicinity to the myocardium the intracoronary ECG icECG is much more sensitive in detecting acute myocardial ischemia The icECG is obtained by attaching a reusable alligator clamp to a coronary guidewire With the guidewire positioned in a coronary artery the derived pseudounipolar icECG reflects local epicardial ECG
The value of the icECG was first shown by Friedman et al Unipolar icECG was recorded during balloon dilatation of coronary stenosis from the guidewire positioned across the stenosis to be dilated Ischemic changes in icECG was observed in 72 of stenoses dilated In the cases with no ischemic changes either a prior myocardial infarction in the territory undergoing balloon dilatation or angiographic collaterals were present consistent with the notion that ischemia was not inducible in nonviable myocardium or prevented by sufficient collaterals Of note ST changes in the surface ECG were seen in only 31 of cases
With acute and complete coronary occlusion perfusion to the dependent territory is usually severely reduced which explains the frequent occurrence of icECG changes However the usefulness of the icECG has also been shown with partial coronary occlusion Experimentally Battler et al demonstrated that during a partial stenosis producing only mild regional dysfunction significant ST segment changes in regional epicardial ECG could be observed after 2-3 minutes Clinically Hishikari et al showed in patients with non-ST-segment elevation myocardial infarction NSTEMI that ST-segment-elevation in the icECG icECG-STE was observed in 276 of patients before PCI and was more common with LCX culprit lesions Furthermore in multivariate analysis icECG-STE predicted greater peak values of troponin levels consistent with greater myocardial injury Similarly but in patients undergoing elective PCI Uetani et al showed that icECG provided a useful method to predict post-procedural myocardial injury
With regard to detection of inducible ischemia by pharmacologic vasodilator stress Balian et al compared STsegment shift in the icECG IST during intravenous adenosine infusion with FFR in 48 patients 81 of patients with an FFR 080 showed IST during adenosine infusion while 14 had IST with an FFR 080 As a major limitation the study compared icECG findings only with FFR and therefore the mechanism of discordant results remained unclear Furthermore the choice of the pharmacologic stressor was questionable the perfusion abnormalities induced by adenosine are the result of flow heterogeneity in contrast to exercise or inotropic pharmacologic stress eg dobutamine where the perfusion abnormalities are the result of myocardial ischemia detectable by the electrocardiogram
Thus the goal of this study is to test the accuracy of intracoronary ic ECG during pharmacologic inotropic stress ie Imitation of daily physical activity to determine significant coronary lesions in comparison with established physiologic indices fractional flow reserve FFR instantaneous wave-free ratio iFR as well as with quantitatively determined percent diameter stenosis S using biplane coronary angiography
In the setting of stable coronary artery disease CAD PCI or coronary artery bypass grafting CABG targets coronary lesions causing inducible myocardial ischemia With the advancement of technology the development of a coronary pressure guide wire enabled to reliably measure coronary perfusion pressure downstream of a stenosis and therefore trans-stenotic pressure gradients On the basis of comparisons to noninvasive stress tests the concept of fractional flow reserve FFR was introduced FFR determines the ratio of mean distal coronary pressure and mean aortic pressure the effective coronary perfusion pressure during pharmacologic hyperemia A FFR value of near 1 is then equivalent to a totally normal coronary artery whereas a cutoff of 075-080 is commonly used to determine that PCI is warranted
With FFR pharmacologic hyperemia is mandatory to induce minimal and constant myocardial resistance which is the basis to directly relate coronary pressure and flowIn contrast the recently introduced concept of the instantaneous wave-free ratio iFR claims to obviate the need for administration of pharmacologic stress Instead coronary pressure is analyzed at rest and during part of coronary diastole when myocardial resistance is thought to be naturally constant and minimal the so called wave-free period
LIMITATIONS OF PRESSURE-DERIVED INDICES OF STENOSIS SEVERITY IN DEFINING THE ISCHEMIC THRESHOLD
A major limitation of pressure-derived indices of stenosis severity is related to the assumption of oversimplified physiologic concepts Clinically the diagnostic accuracy of FFR is restricted in three scenarios Firstly the pressure gradient evaluated by FFR is critically dependent on the magnitude of resistance offered by the microcirculation With microvascular dysfunction microvascular resistance remains inadequately high during pharmacologic hyperemia meaning that the pressure gradient across the stenosis does not reflect the epicardial stenosis severity overestimation of FFR
Secondly with a focal stenosis but well-preserved microvascular function and minimal diffuse atherosclerosis hyperemic coronary flow although reduced may still be above the ischemic threshold although the pressure gradient suggests otherwise Thirdly with severe diffuse coronary atherosclerosis coronary flow may be reduced below the ischemic threshold but with only an insignificant fall in the hyperemic pressure gradient FFR In summary although FFR claims otherwise the ischemic threshold set by FFR is unreliable in a significant proportion of pathophysiological and clinical scenarios
DIRECT ASSESSMENT OF REVERSIBLE MYOCARDIAL ISCHEMIA BY INTRACORONARY ELECTROCARDIOGRAM
The electrocardiogram ECG is an indispensable tool in the diagnosis of myocardial ischemia The commonly used surface ECG is however limited especially in detecting short-lasting or minor myocardial ischemia Furthermore ischemia in the territory of the left circumflex coronary artery is often undetected Conversely due to its close vicinity to the myocardium the intracoronary ECG icECG is much more sensitive in detecting acute myocardial ischemia The icECG is obtained by attaching a reusable alligator clamp to a coronary guidewire With the guidewire positioned in a coronary artery the derived pseudounipolar icECG reflects local epicardial ECG
The value of the icECG was first shown by Friedman et al Unipolar icECG was recorded during balloon dilatation of coronary stenosis from the guidewire positioned across the stenosis to be dilated Ischemic changes in icECG was observed in 72 of stenoses dilated In the cases with no ischemic changes either a prior myocardial infarction in the territory undergoing balloon dilatation or angiographic collaterals were present consistent with the notion that ischemia was not inducible in nonviable myocardium or prevented by sufficient collaterals Of note ST changes in the surface ECG were seen in only 31 of cases
With acute and complete coronary occlusion perfusion to the dependent territory is usually severely reduced which explains the frequent occurrence of icECG changes However the usefulness of the icECG has also been shown with partial coronary occlusion Experimentally Battler et al demonstrated that during a partial stenosis producing only mild regional dysfunction significant ST segment changes in regional epicardial ECG could be observed after 2-3 minutes Clinically Hishikari et al showed in patients with non-ST-segment elevation myocardial infarction NSTEMI that ST-segment-elevation in the icECG icECG-STE was observed in 276 of patients before PCI and was more common with LCX culprit lesions Furthermore in multivariate analysis icECG-STE predicted greater peak values of troponin levels consistent with greater myocardial injury Similarly but in patients undergoing elective PCI Uetani et al showed that icECG provided a useful method to predict post-procedural myocardial injury
With regard to detection of inducible ischemia by pharmacologic vasodilator stress Balian et al compared STsegment shift in the icECG IST during intravenous adenosine infusion with FFR in 48 patients 81 of patients with an FFR 080 showed IST during adenosine infusion while 14 had IST with an FFR 080 As a major limitation the study compared icECG findings only with FFR and therefore the mechanism of discordant results remained unclear Furthermore the choice of the pharmacologic stressor was questionable the perfusion abnormalities induced by adenosine are the result of flow heterogeneity in contrast to exercise or inotropic pharmacologic stress eg dobutamine where the perfusion abnormalities are the result of myocardial ischemia detectable by the electrocardiogram
Thus the goal of this study is to test the accuracy of intracoronary ic ECG during pharmacologic inotropic stress ie Imitation of daily physical activity to determine significant coronary lesions in comparison with established physiologic indices fractional flow reserve FFR instantaneous wave-free ratio iFR as well as with quantitatively determined percent diameter stenosis S using biplane coronary angiography
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None