Safety and prognostic relevance of acetylcholine testing in patients with stable myocardial ischaemia or myocardial infarction and non-obstructive coronary arteries

Rocco Antonio Montone, Riccardo Rinaldi, Marco Giuseppe Del Buono, Filippo Gurgoglione, Giulia La Vecchia, Michele Russo, Andrea Caffè, Francesco Burzotta, Antonio Maria Leone, Enrico Romagnoli, Tommaso Sanna, Gemma Pelargonio, Carlo Trani, Gaetano Antonio Lanza, Giampaolo Niccoli, Filippo Crea, Rocco Antonio Montone, Riccardo Rinaldi, Marco Giuseppe Del Buono, Filippo Gurgoglione, Giulia La Vecchia, Michele Russo, Andrea Caffè, Francesco Burzotta, Antonio Maria Leone, Enrico Romagnoli, Tommaso Sanna, Gemma Pelargonio, Carlo Trani, Gaetano Antonio Lanza, Giampaolo Niccoli, Filippo Crea

Abstract

Background: Intracoronary provocation testing with acetylcholine (ACh) is crucial for the diagnosis of functional coronary alterations in patients with suspected myocardial ischaemia and non-obstructive coronary arteries.

Aims: Our intention was to assess the safety and predictive value for major adverse cardiovascular and cerebrovascular events (MACCE) in patients presenting with ischaemia with non-obstructive coronary arteries (INOCA) or with myocardial infarction with non-obstructive coronary arteries (MINOCA).

Methods: We prospectively enrolled consecutive INOCA or MINOCA patients undergoing intracoronary ACh provocation testing.

Results: A total of 317 patients were enrolled: 174 (54.9%) with INOCA and 143 (45.1%) with MINOCA. Of these, 185 patients (58.4%) had a positive response to the ACh test. Complications during ACh provocative testing were all mild and transient and occurred in 29 (9.1%) patients, with no difference between patients with positive or negative responses to ACh testing, nor between INOCA and MINOCA patients. A history of paroxysmal atrial fibrillation, moderate/severe diastolic dysfunction and a higher QT dispersion at baseline electrocardiogram were independent predictors of complications. MACCE occurred in 30 patients (9.5%) during a median follow-up of 22 months. The incidence of MACCE was higher among patients with a positive ACh test (24 [13.0%] vs 6 [4.5%], p=0.017), and a positive ACh test was an independent predictor of MACCE.

Conclusions: ACh provocation testing is associated with a low risk of mild and transient complications, with a similar prevalence in both INOCA and MINOCA patients. Importantly, ACh provocation testing can help to identify patients at higher risk of future clinical events, suggesting a net clinical benefit derived from its use in this clinical setting.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1. Clinical outcomes according to the…
Figure 1. Clinical outcomes according to the occurrence of complications during ACh provocation test. A.
Incidence of composite of MACCE and individual components of MACCE at follow-up according to the occurrence of complications during an ACh provocation test. B. Incidence of composite of arrhythmic events and individual components of arrhythmic events at follow-up according to the occurrence of complications during an ACh provocation test. C. SAQ summary score at follow-up according to the occurrence of complications during an ACh provocation test. ACh: acetylcholine; AF: atrial fibrillation; AV: atrioventricular; CV: cardiovascular; IQR: interquartile range; MACCE: major adverse cardiovascular and cerebrovascular event; MI: myocardial infarction; SAQ: Seattle Angina Questionnaire; TIA: transient ischaemic attack; UA: unstable angina; VT: ventricular tachycardia
Figure 2. Survival analysis.
Figure 2. Survival analysis.
A. Survival Kaplan–Meier curve for MACCE according to the occurrence of complications during an ACh provocation test. B. Survival Kaplan–Meier curve for MACCE according to a positive or negative ACh invasive provocation test. C. Survival Kaplan–Meier curve for MACCE according to clinical presentation (MINOCA vs INOCA) and response to provocation test (positive vs negative). Curves are compared by the log-rank test. ACh: acetylcholine; INOCA: ischaemia with non-obstructive coronary arteries; MACCE: major adverse cardiovascular and cerebrovascular event; MINOCA: myocardial infarction with non-obstructive coronary arteries
Figure 3. Clinical outcomes according to provocation…
Figure 3. Clinical outcomes according to provocation test response.
A. Incidence of composite of MACCE and individual components of MACCE at follow-up according to a positive or negative ACh invasive provocation test. B. SAQ summary score at follow-up according to a positive or negative ACh invasive provocation test. ACh: acetylcholine; CV: cardiovascular; IQR: interquartile range; MACCE: major adverse cardiovascular and cerebrovascular event; MI: myocardial infarction; SAQ: Seattle Angina Questionnaire; TIA: transient ischaemic attack; UA: unstable angina
Central illustration. Safety and prognostic value of…
Central illustration. Safety and prognostic value of an invasive ACh provocation test.
ACh: acetylcholine; AF: atrial fibrillation; ECG: electrocardiogram; INOCA: ischaemia with non-obstructive coronary arteries; MACCE: major adverse cardiovascular and cerebrovascular event; MINOCA: myocardial infarction with non-obstructive coronary arteries

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