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)

Abstract

The pharmacological provocation test is a pivotal tool in cardiac electrophysiology for the diagnosis of potential causes of sudden cardiac death, sudden cardiac arrest (SCA), arrhythmias, symptoms, or ECG abnormalities. The 2022 European Society of Cardiology Guidelines for the Treatment of Ventricular Arrhythmias and Prevention of Sudden Cardiac Death offered guidance on provocation testing but did not describe the indications and requirements in depth. This clinical consensus statement, led by the European Heart Rhythm Association and approved by major international stakeholders, aims to advise the general cardiologist and the arrhythmia expert who to test and when, where, and how to do it. The statement focuses on current practice for the diagnosis of subclinical arrhythmia syndromes and the causes of SCA, building upon the recommendations of the Guidelines. We address the sodium channel blocker provocation test for patients suspected of Brugada syndrome as well as the use of epinephrine, isoproterenol, adenosine, ergonovine, and acetylcholine.

Keywords: Brugada syndrome; Wolff-Parkinson-White syndrome; acetylcholine; adenosine; ajmaline; cardiac arrest; catecholaminergic polymorphic ventricular tachycardia; coronary vasospasm; drug challenge; epinephrine; ergonovine; flecainide; isoproterenol; pilsicainide; procainamide; provocation testing; sodium channel blocker test; sudden arrhythmic death syndrome; sudden cardiac death.

Figure 1

High precordial lead ECG showing the type 1 Brugada pattern in V1 to V5 with coved ST elevation >2 mm at the J point and associated T wave inversion. The type 2 pattern is evident in V6 with more concave ST elevation. V1 and V2 are in the fourth intercostal space, V3 and V4 represent V1 and V2 in the third intercostal space, and V5 and V6 represent V and V2 in the second intercostal space.

Figure 2

Type 2 and type 3 ECG patterns (panels 1 and 4, respectively) and different methods for measurement. The alpha and beta angles are illustrated in panels 1 and 2, distinguishing between a non-diagnostic type 2 Brugada pattern (panel 1) and benign incomplete RBBB (panel 2). Both angles are greater in patients with likely BrS than in incomplete RBBB and are therefore more likely to be associated with the type 1 Brugada pattern following SCB testing (cut-offs for a positive result: α > 50°, sensitivity 71% and specificity 79%; β > 58°, sensitivity 79% and specificity 83%). The base of the triangle method provides an alternative assessment of the β angle. In panel 3, the base of triangle (C) at 5 mm (0.5 mV—A) from the peak of the R wave is associated with induction of the type 1 Brugada pattern [cut-off C >140 ms (>3.5 mm) sensitivity 81% and specificity 82%]. Similarly, the duration of the base at the isoelectric line (G) illustrated in panel 4 associates with the type 1 Brugada pattern [cut-off G >60 ms (>1.5 mm) 95% sensitivity and 78% specificity] as does the triangle base (G):height (E) ratio. BrS, Brugada syndrome; RBBB, right bundle branch block; SCB, sodium channel blocker.

Figure 3

An example of adjusted high precordial lead placement of V1 and V2 during sodium channel provocation testing. All precordial leads are positioned over the right precordial fourth, third, and second intercostal (ic) spaces. This allows continuous assessment of all leads while the QRS duration can be monitored in the limb leads.

Figure 4

Identifying the J point (defined as the end of the QRS) can be challenging in the presence of R′. The end of the QRS can be identified in a sequentially recorded limb lead. The intersect (B) identifies the J point and C is the degree of ST elevation, from the isoelectric line (PQ and TP segments excluding any U wave) and J point. V1 and V2—fourth intercostal space, V3 and V4—third intercostal space, and V5 and V6—second intercostal space.

Figure 5

A schema for supporting shared decision-making for SCB testing for suspected Brugada syndrome. SCB, sodium channel blocker.

Figure 6

The left panel is a high precordial lead ECG displaying benign partial right bundle branch block with a sharp R′ without J point elevation in leads V1–V5 and a normal axis. BrS is unlikely and SCB testing difficult to justify in the absence of other supportive features. A standard 12-lead ECG is shown on the right panel displaying a type 2 pattern in lead V3. The R′ is broad and there is marked J point elevation >2 mm with a coved ST segment and leftward QRS axis deviation. BrS, Brugada syndrome; SCB, sodium channel blocker.

Figure 7

Example of coronary vasospasm. A practical, video-assisted guide for coronary function testing is available online.