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Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids).

ABSTRACT: Importance:Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk. Objective:To develop and validate an SCD risk prediction model that provides individualized risk estimates. Design, Setting, and Participants:A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017. Exposures:The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping. Main Outcomes and Measures:A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise). Results:Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model's ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95% CI, 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years. Conclusions and Relevance:This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.

SUBMITTER: Norrish G

PROVIDER: S-EPMC6694401 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids).

Norrish Gabrielle G Ding Tao T Field Ella E Ziólkowska Lidia L Olivotto Iacopo I Limongelli Giuseppe G Anastasakis Aristides A Weintraub Robert R Biagini Elena E Ragni Luca L Prendiville Terence T Duignan Sophie S McLeod Karen K Ilina Maria M Fernández Adrián A Bökenkamp Regina R Baban Anwar A Kubuš Peter P Daubeney Piers E F PEF Sarquella-Brugada Georgia G Cesar Sergi S Marrone Chiara C Bhole Vinay V Medrano Constancio C Uzun Orhan O Brown Elspeth E Gran Ferran F Castro Francisco J FJ Stuart Graham G Vignati Gabriele G Barriales-Villa Roberto R Guereta Luis G LG Adwani Satish S Linter Katie K Bharucha Tara T Garcia-Pavia Pablo P Rasmussen Torsten B TB Calcagnino Margherita M MM Jones Caroline B CB De Wilde Hans H Toru-Kubo J J Felice Tiziana T Mogensen Jens J Mathur Sujeev S Reinhardt Zdenka Z O'Mahony Constantinos C Elliott Perry M PM Omar Rumana Z RZ Kaski Juan P JP

JAMA cardiology 20190901 9

<h4>Importance</h4>Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk.<h4>Objective</h4>To develop and validate an SCD risk prediction model that provides individualized risk estimates.<h4>Design, setting, and participants</h4>A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 yea ...[more]

PMID: 31411652

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Project description:BACKGROUND:Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. METHODS:In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy <18 years of age at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest, and aborted SCD, that is, appropriate shock following primary prevention implantable cardioverter defibrillators. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with 10 repeated 4-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized by using the c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe [Sarcomeric Human Cardiomyopathy Registry], n=285). RESULTS:Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated sudden cardiac arrests, and 14 aborted SCD). Risk predictors included age at diagnosis, documented nonsustained ventricular tachycardia, unexplained syncope, septal diameter z-score, left ventricular posterior wall diameter z score, left atrial diameter z score, peak left ventricular outflow tract gradient, and presence of a pathogenic variant. Unlike in adults, left ventricular outflow tract gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated between patients with and without SCD events with a c-statistic of 0.75 and 0.76, respectively, and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72, respectively). CONCLUSION:Our study provides a validated SCD risk prediction model with >70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.

Project description:AimsAtrial fibrillation (AF) and thrombo-embolism (TE) are associated with reduced survival in hypertrophic cardiomyopathy (HCM), but the absolute risk of TE in patients with and without AF is unclear. The primary aim of this study was to derive and validate a model for estimating the risk of TE in HCM. Exploratory analyses were performed to determine predictors of TE, the performance of the CHA2 DS2 -VASc score, and outcome with vitamin K antagonists (VKAs).Methods and resultsA retrospective, longitudinal cohort of seven institutions was used to develop multivariable Cox regression models fitted with pre-selected predictors. Bootstrapping was used for validation. Of 4821 HCM patients recruited between 1986 and 2008, 172 (3.6%) reached the primary endpoint of cerebrovascular accident (CVA), transient ischaemic attack (TIA), or systemic peripheral embolus within 10 years. A total of 27.5% of patients had a CHA2 DS2 -VASc score of 0, of whom 9.8% developed TE during follow-up. Cox regression revealed an association between TE and age, AF, the interaction between age and AF, TE prior to first evaluation, NYHA class, left atrial (LA) diameter, vascular disease, and maximal LV wall thickness. There was a curvilinear relationship between LA size and TE risk. The model predicted TE with a C-index of 0.75 [95% confidence interval (CI) 0.70-0.80] and the D-statistic was 1.30 (95% CI 1.05-1.56). VKA treatment was associated with a 54.8% (95% CI 31-97%, P = 0.037) relative risk reduction in HCM patients with AF.ConclusionsThe study shows that the risk of TE in HCM patients can be identified using a small number of simple clinical features. LA size, in particular, should be monitored closely, and the assessment and treatment of conventional vascular risk factors should be routine practice in older patients. Exploratory analyses show for the first time evidence for a reduction of TE with VKA treatment. The CHA2 DS2 -VASc score does not appear to correlate well with the clinical outcome in patients with HCM and should not be used to assess TE risk in this population.

Project description:BackgroundMaximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort.MethodsThe study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids).ResultsMLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk.ConclusionsIn children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Project description:Background: MRI native T1 mapping and extracellular volume fraction (ECV) are quantitative values that could reflect various myocardial tissue characterization. The role of these parameters in predicting the risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is still poorly understood. Aim: This study aims to investigate the ability of native T1 mapping and ECV values to predict major adverse cardiovascular events (MACE) in HCM, and its incremental values over the 2014 European Society of Cardiology (ESC) and enhanced American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Methods: Between July 2016 and October 2020, HCM patients and healthy individuals with sex and age matched who underwent cardiac MRI were prospectively enrolled. The native T1 and ECV parameters were measured. The SCD risk was evaluated by the 2014 ESC guidelines and enhanced ACC/AHA guidelines. MACE included cardiac death, transplantation, heart failure admission, and implantable cardioverter-defibrillator implantation. Results: A total of 203 HCM patients (54.2 ± 14.9 years) and 101 healthy individuals (53.2 ± 14.7 years) were evaluated. During a median follow-up of 15 months, 25 patients (12.3%) had MACE. In multivariate Cox regression analysis, global native T1 mapping (hazard ratio (HR): 1.446; 95% confidence interval (CI): 1.195-1.749; P < 0.001) and non-sustained ventricular tachycardia (NSVT) (HR: 4.949; 95% CI, 2.033-12.047; P < 0.001) were independently associated with MACE. Ten of 86 patients (11.6%) with low SCD risk assessed by the two guidelines had MACE. In this subgroup of patients, multivariate Cox regression analysis showed that global native T1 mapping was independently associated with MACE (HR: 1.532; 95% CI: 1.221-1.922; P < 0.001). In 85 patients with conflicting results assessed by the two guidelines, end-stage systolic dysfunction was independently associated with MACE (HR: 7.942, 95% CI: 1.322-47.707, P = 0.023). In 32 patients with high SCD risk assessed by the two guidelines, NSVT was independently associated with MACE (HR: 9.779, 95% CI: 1.953-48.964, P = 0.006). Conclusion: The global native T1 mapping could provide incremental values and serve as potential supplements to the current guidelines in the prediction of MACE.

Dataset Information

Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids).

Publications

Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids).

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