Multi-metric Risk Score with Quantitative Late Gadolinium Enhancement Predicts Sudden Death Risk in Patients with Hypertrophic Cardiomyopathy

Extensive late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is considered a modifier of sudden cardiac death risk in hypertrophic cardiomyopathy (HCM).   However, current risk scores estimating SCD risk have not included quantitative LGE as a variable. 

Methods: Consecutive HCM patients from 2 centers underwent CMR and followed prospectively for 6.1 ± 4.5 years. Primary endpoint of SCD events included: sudden death (SCD), aborted cardiac arrest, or appropriate ICD shock.  Multivariable cox regression was used to derive a multi-metric risk score to estimate the 5-year risk of SCD events.

Results:

 There were 1824 patients enrolled (54 ± 15 years; 33% females). Mean LVEF was 62 ± 8%, LV maximal wall thickness was  19± 4mm, and left atrial diameter was  41±7mm. Late gadolinium enhancement was present in 1374  patients (75 %) occupying a median of 3.6% (IQR 0.3,9.6) of the total left ventricular (LV) mass.  At baseline, the prevalence of each AHA/ACC SCD risk factor was as follows:   9.3% had a history of syncope within 5 years before initial CMR,  8.3% had a family history of sudden cardiac death, 26.8.% had a history of non sustained VT (NSVT) on holter monitoring,  2.3% were found to have extreme LVH (LV wall thickness ≥30mm), 7.9% had an apical aneurysm, and 14.6% with ≥15%LGE.  Mean 5-year ESC SCD risk score was 2.8 ± 2.0%.

Over a follow-up of 11058 patient-years, 61 patients (3.3%) experienced the primary SCD end-point, including 52 after the index MRI.  Sudden death occurred in 23 patients, aborted cardiac arrest in 13, and appropriate ICD shock in 27.  Annualized primary event rate was 0.49%, with an estimated 5-year event rate of 1.9 ± 0.4%. 

Univariate Cox regression revealed an increase in SCD risk associated with the following variables (table 1): LGE burden (p< 0.0001), maximal wall thickness (p< 0.001), LA diameter (p< 0.0001), family history of SCD (p=0.001), NSVT (p=0.057), LV mass (p=0.012), lower LVEF (p< 0.0001), presence of a pathogenic mutation (p=0.02), LVEDV (p=0.002), LVESV (p< 0.0001), lower age of diagnosis (p=0.03), and ESC Risk Score (p=0.0003).

Multivariable Cox regression using stepwise selection revealed 5 variables to be independently associated with increased SCD risk (table 1): 1) LGE burden (p< 0.0001), 2) Maximal wall thickness (p=0.024), 3) LA diameter (p=0.0027), 4) Family history of SCD (p=0.0012), and 5) LV end systolic volume (p=0.0003).

The five year SCD risk can be estimated by the following equation:

P _{SCD at 5 years}= 1- 0.982 ^{exp (prognostic index)}

Where prognostic index = 0.01737 (%LGE) + 0.06037*(Maximal wall thickness-19)+ 0.06213*(LA diameter-41 ) + 1.20907*(Family history of SCD) + 0.01134*(LVESV- 61)

The c-statistic for this multiparametric model is 0.78 (95% CI 0.76-0.80), compared with the c-statistic of the ESC risk score of 0.67 (95% CI 0.65-0.69)

Conclusion: This is the first multi-metric risk score which integrates quantitative LGE and CMR metrics to provide prognostic estimates of SCD risk in patients with hypertrophic cardiomyopathy.