eTable. The risk factors for sudden cardiac death.
| Risk factor for sudden cardiac death (SCD) | Description |
| Massive left ventricular (LV) hypertrophy (LV wall thickness ≥ 30 mm)*1,*3 | • The SCD risk rises with increasing LV wall thickness. Data expressed as SCD risk per 1000 person years [95% confidence interval]. The SCD risk is 0 [0; 14.4] for a maximal LV wall thickness of ≤ 15 mm, 2.6 [0.3; 9.6] for LV wall thickness 16–19 mm, 7.4 [3.5; 13.6] for LV wall thickness 20–24 mm, 11.0 [3.0; 28.2] for LV wall thickness 25–29 mm, and 18.2 [7.3; 37.6] for LV wall thickness of ≥ 30 mm (e27). • Extreme LV wall thickness of ≥ 30 mm was observed mainly in younger patients (in an observational study with 480 patients the mean age of the whole cohort was 47 years and the mean age of the patients with extreme LV wall thickness was 31 years; of 12 patients < 18 years with extreme lv hypertrophy, 5 died from scd [e27]). |
| Positive family history of SCD*1, *3 | • There are various definitions of a positive family history: • ESC definition: SCD in ≥ 1 first-degree relative < 40 years, independent of whether hcm/hocm was diagnosed, or scd in a first-degree relative of any age if hcm/hocm was diagnosed (4). • AHA definition: SCD in ≥ 1 first-degree relative independent of age or in second-degree relatives < 50 years or ≥ 2 scd in third-degree relatives (32). • Hazard ratio (HR) 1.76 [1.32; 2.4] for SCD-related 5-year mortality with positive family history (e28) |
| Unexplained, most likely arrhythmogenic syncope*1, *3 | • Assessment is often difficult because of the large number of potential causes. • Syncope in the previous 6 months is associated with a particularly high risk of SCD (HR 4.89 [2.19; 10.94]), while unexplained syncopes > 5 years earlier in older patient (≥ 40 years) are not associated with an elevated SCD risk (HR 0.38 [0.05; 2.74] (e29). • An unexplained syncope in a young patient is a strong risk factor for SCD. In patients < 18 years with unexplained syncope the hr for scd is 8.01 [2.07; 31.45] (e29). • In an observational study with 3675 HCM/HOCM patients the HR was 2.33 [1.69; 3.2] for SCD-related 5-year mortality in the presence of unexplained syncopes (e28) |
| Left ventricular ejection fraction (LVEF) < 50%*1 | • One study observed 2447 HCM/HOCM patients, of whom 118 had LVEF ≤ 49%. The SCD rate per year was 2.4% versus 0.5% in the remaining 2329 patients with LVEF > 50% (e30). |
| Apical LV aneurysm*1 | • Only a small proportion of patients form an apical aneurysm (ca. 4.8%) with transmural fibrosis (detectable on MRI) (e31). • The risk of SCD is greatly increased. A study that followed 1940 HCM/HOCM patients, of whom 93 (4.8%) had an apical aneurysm, observed an annual SCD rate of 4.7% in patients with apical aneurysm vs. 0.9% in the remaining 1847 patients without apical aneurysm (e31). |
| Pronounced late gadolinium enhancement (LGE) on cardiac MRI (≥ 15%)*2 | • LGE is a marker of fibrosis and can be detected on cardiac MRI. The extent of LGE in relation to LV mass can be expressed in %. • Around 50% of patients with HCM/HOCM have LGE (e32) • A meta-analysis of 5 studies and 2993 HCM/HOCM patients concluded that the SCD risk rises with increasing LGE. HR of 1.56 [1.33; 1.82] per 10% LGE reported (e33). • One study explored the risk of SCD depending on the extent of LGE over an observation period of 7 years. Patients with ≤ 15% LGE had an elevated SCD risk (HR 1.4). In patients with LGE > 15% the HR for the occurrence of SCD was 2.84 [1.27; 6.34] for those with HCM and 3.04 [1.48; 6.10] for HOCM (e32). |
| Non-sustained ventricular tachycardia (NSVT) on long-term ECG*2, 3 | • Definition: ventricular tachycardia ≥ 3 consecutive ventricular beats with heart rate ≥ 120 bpm and duration < 30 s (4, 32) • Approximately 20% of HCM/HOCM patients have NSVT on long-term ECG. • HR 2.29 [1.64; 3.18] for SCD-related 5-year mortality when NSVT are found on long-term ECG (e28) • NSVT in young patients shows a greatly increased risk of SCD. In one study with 104 patients the OR for SCD was 4.35 [1.54; 12.28] in patients with NSVT ≤ 30 years and 2.16 [0.82; 5.69] for patients > 30 years (e34). |
| Age (higher risk at younger age)*3 | • Younger patients are at higher risk of SCD. NSVT (e34), extreme LV hypertrophy (e27), or unexplained syncope (e29) indicate particularly high risk. |
| Size of left atrium*3 | • In a study that explored the link between syncopes and SCD by observing 1511 patients, multimodal regression analysis was carried out. The identified independent risk factors for SCD included enlargement of the left atrium (relative risk 1.03 [1.00; 1.06]). Another study also associated left atrial enlargement with a significantly increased risk of SCD, HR 1.035 [1.018; 1.052] (e28). |
| Left ventricular outflow tract (LVOT) obstruction*3 | • An LVOT obstruction with LVOT gradient ≥ 30 mm Hg increases the risk of SCD with a HR of 1.84 [1.14; 2.98] (e35). • Another observational study with 917 patients showed that LVOT obstruction increases the risk of SCD 2.4-fold compared with patients without LVO obstruction (e36). |
*1 Classified as a major risk factor by the AHA (if ≥ 1 risk factor is present, ICD placement should be considered [class of recommendation (COR) IIa (“can be useful”)], level of evidence [LOE] B-NR (evidence from ≥ 1 non-randomized study, observational study, or registry study)
*2 Classified as an important risk factor by the AHA,but with a weaker recommendation for ICD placement (if ≥ 1 risk factor is present, ICD placement can be considered [COR IIb (“unknown usefulness”)], LOE B-NR),
*3 Is considered in the ESC’s HCM Risk-SCD score and influences the ESC recommendation concerning ICD placement. If the HCM Risk-SCD score indicates low risk (5-year mortality < 4%) with ≥ 1 further clinical risk factor or intermediate risk (5-year mortality 4–6%), ICD placement can be considered (COR IIb [“unknown usefulness”]), LOE B [evidence from one randomized clinical trial or > 1 large non-randomized study]). In the case of high risk (5-year mortality ≥ 6%), ICD placement should be considered (COR IIa [“can be useful”], LOE B).
ECG, Electrocardiogram; HCM, hypertrophic cardiomyopathy; HOCM, hypertrophic obstructive cardiomyopathy; MRI, magnetic resonance imaging