Clinical trial NCT05583786: Intracoronary ECG ST-segment Shift Remission Time During Reactive Coronary Hyperemia
Official title: Intracoronary ECG ST-segment Shift Remission Time During Reactive Coronary Hyperemia, τ-icECG: a New Method for Assessing Hemodynamic Stenosis Severity
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Coronary Syndrome
Keywords: Intracoronary electrocardiogram
icECG
Reactive-hyperemia
Balloon occlusion
Fractional flow ratio
FFR
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2022-10-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with chronic coronary syndrome electively referred to the investigators department for coronary angiography.

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: icECG ST-segment shift remission time (τ-icECG)
timeFrame: once after a 1-minute coronary ballon occlusion
Secondary outcomes:
measure: Quantitative percent diameter narrowing (secondary reference) (%S)
timeFrame: once after a 1-minute coronary ballon occlusion
measure: Reactive hyperemia FFR (primary reference)
timeFrame: once after a 1-minute coronary ballon occlusion
measure: Instantaneous wave-free ratio (iFR)
timeFrame: once before a 1-minute coronary ballon occlusion
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselspital
Study officials:
affiliation: Inselspital
name: Christian Seiler, Prof
role: PRINCIPAL_INVESTIGATOR
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