The diagnostic role of pharmacological provocation testing in cardiac electrophysiology: a clinical consensus statement of the European Heart Rhythm Association and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, the ESC Working Group on Cardiovascular Pharmacotherapy, the Association of European Paediatric and Congenital Cardiology (AEPC), the Paediatric & Congenital Electrophysiology Society (PACES), the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS). Europace. 2025 Mar 28;27(4):euaf067. doi: 10.1093/europace/euaf067. PMID: 40165484; PMCID: PMC12018878.
Diagnosing an (inherited) cardiac disease in cardiac electrophysiology (tests performed to assess a heart’s electrical system) is not always straightforward. Sometimes an extra diagnostic test is needed by using a drug to unmask for example a specific ECG (electrocardiogram) pattern (i.e. a drug or pharmacological provocation test). In general, a diagnostic pharmacological provocation test offers a controlled environment to diagnose the potential causes of sudden cardiac death (SCD), sudden cardiac arrest (SCA), arrhythmias, symptoms or ECG (abnormalities. Well known examples are the sodium blocker challenge for Brugada syndrome (most common drugs used are ajmaline and flecainide) or an epinephrine (drug) test to unmask Long QT syndrome.
The 2022 European Society of Cardiology Guidelines for the Treatment of Ventricular Arrhythmias and Prevention of Sudden Cardiac Death (2022 ESC VA SCD) offered guidance on provocation (to provoke) testing but did not describe the indications and requirements in depth (give a detailed explanation). This clinical consensus statement aims to advise the general cardiologist and the arrhythmia expert who to test and when, where and how to do it, with a focus on current practice for the diagnosis of subclinical (no obvious or noticeable signs or symptoms) arrhythmia syndromes and the causes of SCA. The recommendations of the previously mentioned Guidelines are the building stones of this document also.
The pharmacological provocation tests that are discussed in detail are the sodium channel blocker test to unmask Brugada syndrome, the epinephrine/isoproterenol test to unmask LQTS or CPVT, adenosine to unmask WPW syndrome (a syndrome associated with mostly benign arrhythmias) and acetylcholine to unmask spasm of the coronary arteries (i.e. (uncontrolled contractions of the coronary vessel wall leading to temporarily ischemia of a certain part of the heart). The indications and contraindications, outcome results (how to interpret the test results), side effects and the best way to perform the test are all extensively discussed. This document offers physicians a guide to carefully choose the right test for the right patient and when decided it should be performed, how it best performed.
Behr ER, Winkel BG, Ensam B, Alfie A, Arbelo E, Berry C, Cerrone M, Conte G, Crotti L, Corcia CMG, Kaski JC, Nademanee K, Postema PG, Priori S, Probst V, Sarquella-Brugada G, Schulze-Bahr E, Tadros R, Wilde A, Tfelt-Hansen J, Wolpert C, Cuesta A, Damman P, Dobrev D, Drago F, Haugaa K, Krahn A, Krause U, Lambiase PD, Napolitano C, Odening KE, Shimizu W, Veltmann C.
Prepared by Arthur Wilde and Lorraine McGlinchey