Intracoronary ECG ST-segment Shift Remission Time During Reactive Coronary Hyperemia

Study Overview
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Brief Summary
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This study evaluates a new diagnostic approach based on intracoronary electrocardiogram (icECG) ST-segment shift remission time, denoted as τ-icECG (τ=tau, i.e., the remission half-time fitted by an exponential function to the disappearing ST-segment shift), to be used for PCI guidance.

Detailed Description
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Cardiovascular disease is the major cause of death globally, accounting for 17.9 million deaths per year in 2019. Aside from the acute coronary syndrome, where percutaneous coronary intervention (PCI) has been shown to improve outcome, the number of patients with chronic coronary syndrome (CCS) is also increasing. PCI of hemodynamically relevant stenotic lesions causing myocardial ischemia is the standard treatment in these patients. Effective revascularization, as recommended by the European Society of Cardiology (ESC) guidelines, requires to differentiate between hemodynamically relevant and non-significant stenotic coronary lesions. Currently, coronary stenosis assessment is performed by structural visual angiographic assessment or by coronary pressure measurements up- and downstream of the lesion. The latter is recommended by the ESC and is based on its prognostic value derived from large randomized clinical trials. Given temporary paralysis of the coronary microcirculation by a hyperemia-inducing substance such as adenosine (ADO), pressure is, in theory, directly related to coronary flow. Therefore, the pressure drop during hyperemia across a coronary stenosis, i.e., fractional flow reserve (FFR) provides an estimate of its restrictive effect on flow. However, this method depends on expensive pressure sensor angioplasty guidewires, and on hyperemia-inducing substances, such as ADO. Hence, pharmacologic limitations such as atrioventricular conduction defects and asthma and other potential adverse events (e.g. arrhythmias) aside from costs are major drawbacks of pressure-derived FFR. In order to avoid potential drug-induced side effects and achieve maximal hyperemia, the study group performs reactive hyperemia FFR measurements induced by a proximal, 1-minute coronary artery balloon occlusion. This method has been documented non-inferior in its ability to detect relevant coronary stenosis compared to adenosine-induced FFR. The present project aims at validating a novel, potentially more harmless, faster and less costly diagnostic approach for measuring hemodynamic coronary stenosis severity. The commonly obtained surface lead electrocardiogram (ECG) is limited in detecting short-lasting or minor myocardial ischemia. In comparison, intracoronary ECG (icECG) is more time- and space-sensitive in detecting myocardial ischemia, the latter being due to its close vicinity to the myocardial region of interest. It can be easily obtained by attaching an alligator clamp to a coronary guidewire. Based on the sensitivity of the icECG, several clinical trials have assessed the value of icECG to guide PCI, and rated it useful to predict post-procedural myocardial injury. The investigators research group performed a trial to determine the diagnostic accuracy of icECG ST-segment shift during pharmacologic inotropic stress in assessing functional coronary lesion severity versus structural stenosis severity as obtained by quantitative coronary angiography in % diameter narrowing (%S by QCA), and versus other functional hemodynamic indices (FFR, instantaneous wave-free ratio (iFR)). IcECG ST-segment shift showed a significant correlation with all established parameters. Evaluation of icECG required the development of a specific software algorithm, which robustly determines quantitative icECG ST-segment shift in every single heartbeat. The validation analysis of the algorithm took place in an offline setting and demonstrated an excellent correlation as compared to the results of ECG experts (r2 = 0.932; p<0.001). The development of this fully autonomous icECG analyzing algorithm was set up on an existing ECG software, denoted as EsoLive, developed at the Institute for Medical Engineering and Medical Informatics, University of Applied Sciences and Arts Northwestern Switzerland. In short, the algorithm starts with a baseline wander extraction method related to Kalman filtering, then sets the initial points for an edge, i.e., J-point, before, it processes in a similar way the isoelectric line level. Quantitative time as well as voltage measurements of those two points allow the calculation of the icECG ST-segment shift for each single QRS complex. This study evaluates a new diagnostic approach based on icECG ST-segment shift remission time, denoted as τ-icECG (τ=tau, i.e., the remission half-time fitted by an exponential function to the disappearing ST-segment shift), to be used for PCI guidance.

Official Title
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Intracoronary ECG ST-segment Shift Remission Time During Reactive Coronary Hyperemia, τ-icECG: a New Method for Assessing Hemodynamic Stenosis Severity

Conditions
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Chronic Coronary Syndrome

Intervention / Treatment
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* Diagnostic Test: Tracing intracoronary electrocardiogram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic coronary syndrome Chronic stable 1-3 vessel coronary artery disease Coronary stenotic lesion of any diameter narrowing Age > 18 years Referred for elective coronary angiography to the investigators institution Written informed consent to participate in the study Exclusion Criteria: Acute coronary syndrome Unstable cardiopulmonary condition Severe aortic valve stenosis Acute congestive heart failure NYHA (New York Heart Association) III-IV ECG bundle branch blocks, non-sinus rhythm or paced rhythm Coronary anatomy unsuitable for coronary measurements Severe pulmonary, renal or hepatic disease Women of childbearing age (≤50years and ≤12months after the last menstruation)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Tracing intracoronary electrocardiogram|icECG ST-segment shift remission time (τ-icECG) tracing during reactive-hyperemia, obtained immediately after a 1-minute upstream coronary artery balloon occlusion.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| icECG ST-segment shift remission time (τ-icECG) | The primary study objective is to test reactive hyperemia τ-icECG as obtained immediately after a 1-minute upstream coronary artery balloon occlusion as a new method to determine the hemodynamic significance of a coronary artery stenosis. As primary reference method, reactive hyperemia FFR (cut-off 0.80) is employed. | once after a 1-minute coronary ballon occlusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative percent diameter narrowing (secondary reference) (%S) | The secondary study objective is to test reactive hyperemia τ-icECG against the structural reference of a coronary artery stenosis, %S, and to compare the accuracy of τ-icECG against reactive hyperemia FFR, and instantaneous wave-free ratio (iFR). | once after a 1-minute coronary ballon occlusion | 
| Reactive hyperemia FFR (primary reference) | The secondary study objective is to compare the accuracy of τ-icECG against reactive hyperemia FFR. | once after a 1-minute coronary ballon occlusion | 
| Instantaneous wave-free ratio (iFR) | The secondary study objective is to compare the accuracy of τ-icECG against iFR. | once before a 1-minute coronary ballon occlusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracoronary electrocardiogram, icECG, Reactive-hyperemia, Balloon occlusion, Fractional flow ratio, FFR