Methodology.

The study was approved by our institutional ethics committee (Alfred Health Ethics Research Administration) as a low-risk project. Records were reviewed for all patients under the age of 60 who underwent implantation of a secondary prevention implantable cardiac defibrillator (ICD) between January 2010 and July 2021 at a single quaternary cardiology centre in Melbourne, Australia. Secondary prevention ICD was defined in our study as a device implanted after a clinical presentation with either 1) ventricular tachyarrhythmias resulting in syncope and/or cardiac arrest, or 2) conscious sustained ventricular tachycardia. We included patients receiving both subcutaneous ICDs and transvenous devices, with the transvenous devices comprising single chamber ICDs, dual chamber ICDs and biventricular ICDs.
Records were reviewed for all cardiac investigations performed as part of the diagnostic evaluation in these device recipients, defined as investigations performed either within 3 months prior to device implant or within 6 months following device implant. Baseline ECGs were accessed to record rhythm, cardiac axis, QT interval and the presence or absence of the early repolarisation pattern. Transthoracic echocardiography (TTE) records were accessed to collect both qualitative parameters (overall left and right ventricular function, presence of segmental hypokinesis, degree of valvular dysfunction) and quantitative parameters (LV diastolic diameter and left ventricular ejection fraction). Investigations for coronary artery disease, including invasive coronary angiography and computerised tomographic coronary angiography (CTCA), were accessed to record the presence of obstructive coronary artery disease, defined as >70% luminal stenosis, and requirement for follow-on coronary revascularisation.
We then identified a cohort of patients with unexplained ventricular arrhythmias (UVA, Group 1) in whom the aetiology for ventricular arrhythmia remained unexplained after three ‘first-line’ cardiac investigations: TTE, ECG and coronary assessment (Table 1). More specifically, patients with UVA were defined as those structurally normal heart on TTE, absence of obstructive disease on coronary assessment and no clear diagnostic features on ECG. Examples of clear diagnostic features on ECG included long or short QT intervals, features of arrhythmogenic right ventricular cardiomyopathy (ARVC), features of Brugada syndrome or manifest pre-excitation.
We compared this UVA cohort of patients with patients having a confirmed or strongly suspected aetiology of their ventricular arrhythmia on the basis of 12-lead ECG, TTE and coronary assessment. This group was labelled was labelled VA with clear aetiology (Group 2).
We then evaluated the adoption rate of five modalities of ‘second-line’ investigations for ventricular arrhythmia in both groups. These second-line investigations included cardiac magnetic resonance imaging (CMR), exercise stress ECG, flecainide challenge, electrophysiology studies (EP) and genetic testing. Where these investigations were available, we recorded whether the result elucidated the underlying aetiology of the presenting ventricular arrhythmia.
Clinical discharge summaries were reviewed to determine which antiarrhythmic drugs were prescribed to patients following presentation with a ventricular arrhythmia. We recorded rates of prescription of beta blockers, amiodarone, flecainide and sotalol.
Finally, we sought to evaluate outcome data for patients with respect to future burden of ventricular arrhythmia and all-cause mortality. We reviewed all available records from subsequent device interrogations for the first five years following device implantation. In order to be included for this phase of the analysis, patients were required to have documentation of at least two device interrogation reports over this five-year period. We assessed for the frequency of device-detected NSVT and requirement for tachycardia therapies, including anti-tachycardia pacing (ATP) and device-delivered shocks. Hospital records were reviewed to assess for patient mortality up to 10 years following device implant.