Predictors of recurrent ventricular arrhythmias and the impact of genetic testing in a hypertrophic cardiomyopathy patient cohort at long term follow up

Background/Introduction

Patients with hypertrophic cardiomyopathy (HCM) are at risk of sudden cardiac death (SCD) due to ventricular arrhythmias. Implantable cardioverter defibrillators (ICD) prevent SCD but are associated with adverse events, particularly in younger patients. The European Society of cardiology (ESC) recommend using an HCM-risk score for ICD shared decision making (1). A 5 years SCD risk of 6% or more has a Class IIa indication for an ICD. A 5 years risk of 4-6%, an ejection fraction under 50% or extensive (>15%) late gadolinium enhancement (LGE) on MRI has a Class IIb recommendation. Genetic variants are not recommended as an independent predictor of SCD based on a small number of studies. Identifying which patients are most at risk may help guide the decision to implant an ICD.

Purpose

To determine the characteristics of patients with HCM who:

- Have ventricular arrythmias after ICD implant.

- Have a genetic variant identified.

Methods

Cases of HCM were identified through the electronic databases at our centre. The electronic health records were reviewed to identify baseline demographics, left ventricular outflow tract gradient, SCD risk score, genotype, and ICD therapy. Predictors of ventricular arrhythmias were identified from ESC guidelines(1).

Results

73 HCM patients were identified (mean age 60 ± 12, 63% male). 36 (49%) patients had genetic testing. 16 patients (44%) had a genetic variant identified, MYBPC3 (9) and MYH7 (5). No patients with apical HCM had a gene variant. The average age at diagnosis was 46 years (± 12) for patients with a genetic variant compared to 56 years (± 13) in patients without (p=0.007).

32 (44%) patients had an ICD, 7 (22%) were a single chamber ICD and 25 (78%) a dual chamber ICD. The median follow up was 5 years 5 months (IQR 3 years - 9 years). 8 (25%) patients had complications, mainly RV lead related. 6 (19%) patients had device therapy with either a shock (4) or ATP (2). 2 (6%) had inappropriate shocks. Baseline characteristics between the two groups were similar (Figure 2).

The strongest and only statistically significant predictor for ICD therapy was an ESC risk score of 6% and over. 67% of patients receiving ICD therapy had a risk score over 6% compared with 15% of patients not receiving ICD therapy (p=0.031). Implantation of a device for an SCD risk score of 6% and over was associated with a significant increase in subsequent ICD therapy (OR 11 (1.48 to 81.6 p=0.019)).

Conclusion(s)

The strongest predictor of ICD therapy in our cohort was a SCD risk score of 6% and over. In keeping with previous studies identification of a genetic variant did not increase ICD therapies but patients were diagnosed with HCM at an earlier age. Unlike current guidelines extensive LGE scar did not predict ICD therapy in this small study. Appropriate SCD risk scoring continues to be important when counselling younger patients about ICD implant.Figure 1Figure 2