A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD)
Open accessAbstract
AIMS: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) in young adults. Current risk algorithms provide only a crude estimate of risk and fail to account for the different effect size of individual risk factors. The aim of this study was to develop and validate a new SCD risk prediction model that provides individualized risk estimates. METHODS AND RESULTS: The prognostic model was derived from a retrospective, multi-centre longitudinal cohort study. The model was developed from the entire data set using the Cox proportional hazards model and internally validated using bootstrapping. The cohort consisted of 3675 consecutive patients from six centres. During a follow-up period of 24 313 patient-years (median 5.7 years), 198 patients (5%) died suddenly or had an appropriate implantable cardioverter defibrillator (ICD) shock. Of eight pre-specified predictors, age, maximal left ventricular wall thickness, left atrial diameter, left ventricular outflow tract gradient, family history of SCD, non-sustained ventricular tachycardia, and unexplained syncope were associated with SCD/appropriate ICD shock at the 15% significance level. These predictors were included in the final model to estimate individual probabilities of SCD at 5 years. The calibration slope was 0.91 (95% CI: 0.74, 1.08), C-index was 0.70 (95% CI: 0.68, 0.72), and D-statistic was 1.07 (95% CI: 0.81, 1.32). For every 16 ICDs implanted in patients with ≥4% 5-year SCD risk, potentially 1 patient will be saved from SCD at 5 years. A second model with the data set split into independent development and validation cohorts had very similar estimates of coefficients and performance when externally validated. CONCLUSION: This is the first validated SCD risk prediction model for patients with HCM and provides accurate individualized estimates for the probability of SCD using readily collected clinical parameters.
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A history of syncope in patients with structural heart disease or inheritable arrhythmia syndromes is associated with a two- to four-fold increased risk of death, but this varies between specific conditions.
“In general, a history of syncope in patients with structural heart disease or inheritable arrhythmia syndromes is associated with a two- to four-fold increased risk of death, 348,350-353 but varies between specific conditions. 354-356”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [350]
The Methods and results (p. 1) identify unexplained syncope as associated with sudden cardiac death or an appropriate ICD shock in patients with hypertrophic cardiomyopathy. This supports an association in one structural heart condition, but the passage does not establish a two- to four-fold increase in risk of death across structural heart diseases and inheritable arrhythmia syndromes. The separate claim that risk varies between conditions is attached to other citations. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the largest multicentre study to date, with more than 3600 patients with hypertrophic cardiomyopathy, syncope was an independent predictor of the composite of sudden cardiac death and ICD discharge (hazard ratio 2.05, 95% CI 1.48-2.82).
“In the largest multicentre study to date (>3600 patients with HCM), syncope was an independent predictor of the composite of SCD and ICD discharge (hazard ratio 2.05, 95% CI 1.48-2.82). 350”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [350]
Methods and results (p. 1) describe a six-centre cohort of 3,675 patients and the composite endpoint of sudden cardiac death or appropriate ICD shock. Model development (p. 4) includes unexplained syncope as a predictor with a coefficient of 0.71650361, corresponding to a hazard ratio of about 2.05. The passages retrieved do not establish the stated 95% confidence interval or that this was the largest multicentre study to date. (LLM, conf=0.82)
Experimental — accuracy not yet measured
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Nielsen, J. C., Lin, Y.-J., de Oliveira Figueiredo, M. J., Sepehri Shamloo, A., Alfie, A., Boveda, S., Dagres, N., Di Toro, D., Eckhardt, L. L., Ellenbogen, K., et al. (2020) · EP Europace · doi:10.1093/europace/euaa065 · Cited by 98 · see citing works
- Authors
- O'Mahony, C., Jichi, F., Pavlou, M., Monserrat, L., Anastasakis, A., Rapezzi, C., Biagini, E., Gimeno, J. R., Limongelli, G., McKenna, W. J., Omar, R. Z., Elliott, P. M., & for the Hypertrophic Cardiomyopathy Outcomes Investigators
- Affiliations
- University College London (GB)
- National and Kapodistrian University of Athens (GR)
- University of Bologna (IT)
- Hospital Universitario Virgen de la Arrixaca (ES)
- University of Campania "Luigi Vanvitelli" (IT)
- University College Hospital at Westmoreland Street (GB)
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-14
- Volume
- 35
- Issue
- 30
- Pages
- 2010-2020
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2119361626
- Cited by
- 1,251
- References
- 50
- Citations by year
- 2026: 107 · 2025: 124 · 2024: 115 · 2023: 120 · 2022: 99 · 2021: 125 · 2020: 116 · 2019: 87 · 2018: 81 · 2017: 100 · 2016: 67 · 2015: 76 · 2014: 31 · 2013: 2
- FWCI
- 39.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Hispana (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, other-oa)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (NF-SI-0509-10230)
- Università di Bologna
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- hypertrophic cardiomyopathy, sudden cardiac death, risk prediction model, individualized risk estimation, implantable cardioverter-defibrillator, left ventricular wall thickness, left ventricular outflow tract gradient, family history of sudden cardiac death, non-sustained ventricular tachycardia, unexplained syncope, left atrial diameter, model validation
- MeSH terms
- Adult, Cardiomyopathy, Hypertrophic, Female, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Reproducibility of Results, Proportional Hazards Models, Death, Sudden, Cardiac, Sample Size, Risk Assessment
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