Airflow obstruction, impaired lung function and risk of sudden cardiac death: a prospective cohort study

BackgroundGrowing evidence suggests that compromised lung health may be linked to cardiovascular disease. However, little is known about its association with sudden cardiac death (SCD).ObjectivesWe aimed to assess the link between impaired lung function, airflow obstruction and risk of SCD by race and gender in four US communities.MethodsA total of 14 708 Atherosclerosis Risk in Communities (ARIC) study participants who underwent spirometry and were asked about lung health (1987–1989) were followed. The main outcome was physician-adjudicated SCD. Fine-Gray proportional subdistribution hazard models with Firth’s penalised partial likelihood correction were used to estimate the HRs.ResultsOver a median follow-up of 25.4 years, 706 (4.8%) subjects experienced SCD. The incidence of SCD was inversely associated with FEV1 in each of the four race and gender groups and across all smoking status categories. After adjusting for multiple measured confounders, HRs of SCD comparing the lowest with the highest quintile of FEV1 were 2.62 (95% CI 1.62 to 4.26) for white males, 1.80 (95% CI 1.03 to 3.15) for white females, 2.07 (95% CI 1.05 to 4.11) for black males and 2.62 (95% CI 1.21 to 5.65) for black females. The above associations were consistently observed among the never smokers. Moderate to very severe airflow obstruction was associated with increased risk of SCD. Addition of FEV1 significantly improved the predictive power for SCD.ConclusionsImpaired lung function and airflow obstruction were associated with increased risk of SCD in general population. Additional research to elucidate the underlying mechanisms is warranted.

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Spirometric Findings among School-Aged First Nations Children on a Reserve: A Pilot Study

Canadian Respiratory Journal ◽

10.1155/2004/427686 ◽

2004 ◽

Vol 11 (1) ◽

pp. 45-48 ◽

Cited By ~ 5

Author(s):

Don D Sin ◽

Heather M Sharpe ◽

Robert L Cowie ◽

SF Paul Man ◽

Keyword(s):

Pilot Study ◽

Lung Function ◽

First Nations ◽

School Health ◽

Airflow Obstruction ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Parental Report ◽

Increased Risk ◽

Impaired Lung Function

BACKGROUND:Asthma and chronic obstructive pulmonary disease (COPD) are increasing concerns for First Nations peoples in Canada. Although hospital utilization for asthma and COPD among First Nations peoples has been increasing, the prevalence of asthma or wheezing is comparable to national averages.OBJECTIVES:A pilot study was conducted to determine the prevalence of impaired lung function in school-aged First Nations children.PATIENTS AND METHODS:A First Nations community in northern Alberta was selected to participate. Consent forms and a school health survey were completed by parents or guardians. Children with consent completed spirometry at school, and results were compared with predicted values.RESULTS:A total of 36 children participated (response rate 70.6%). Of these, 19.4% of parents reported that their child had received a physician diagnosis of asthma at some point in their life; only 28.6% had a parental report of still having asthma. Parents smoked in 73.1% of the children's homes. The mean (± SD) percentage of forced expiratory volume in 1 s (FEV1) over forced vital capacity (FVC) was 82.6%±6.9% (94.4%±0.08% of predicted). Evidence of airflow obstruction was found in 25% of the children. Parental report of the child ever having asthma was associated with impaired lung function (OR 3.20; P=0.033). Children in a home with reported mold exposure were less likely to have impaired lung function (OR 0.68; P=0.030).CONCLUSIONS:Many children in this study already have established airflow obstruction and may be at increased risk for asthma or COPD. Exposure to mold appeared to be protective. Further research is needed to evaluate the lung health concerns of this population.

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Association between digoxin use and sudden cardiac death in individuals with the rs10494366 variant of the NOS1AP gene

European Heart Journal ◽

10.1093/ehjci/ehaa946.3394 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

N Soroush ◽

A Aarnoudse ◽

F Shokri ◽

M Van Den Berg ◽

F Ahmadizar ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Death ◽

Smoking Status ◽

Adaptor Protein ◽

Therapeutic Window ◽

P Value ◽

Qtc Interval ◽

Total Study Population ◽

Increased Risk

Abstract Background Digoxin is one of the oldest cardiovascular medications still used to treat heart failure and atrial fibrillation. Due to its narrow therapeutic window, it is associated with life threatening intoxication and arrhythmias, and with QTc-shortening. Common genetic variation in the nitric oxide synthase-1 adaptor protein (NOS1AP) has been associated with QTc interval prolongation. Purpose We investigated whether the rs10494366 variant of the NOS1AP gene modified the risk of SCD in patients using digoxin. Methods In a prospective population-based cohort study, we included data of the three cohorts, started as of January 1st, 1991 until January 1st 2014. Digoxin current use on the date of cardiac death in cases and the same day of follow-up in the remainder of the cohort was a time-dependent exposure. The main outcome was SCD defined as sudden and unexpected death as a result of cardiac causes, according to international criteria. Identification and adjudication of SCD was performed independently, before the start of this study. We used Cox proportional hazard regression analysis to investigate the associations between NOS1AP rs10494366 variant and incident SCD among digoxin users compared to non-users. Associations were adjusted for age, sex (model 1) in addition to BMI, prevalent diabetes, myocardial infarction, baseline hypertension and smoking status (past, current, never) (model 2). Results We included 14,594 individuals, with a mean age of 65.3 (SD 10.3) years. Almost 59% were female. The cumulative incidence of SCD was 9.5% (609 cases) by the end of follow up. Among them, 98 (16%) individuals were exposed to digoxin at the time of death. In model 1, NOS1AP rs10494366 variant was not associated with SCD in the total study population. However, an interaction term of the gene with the daily dose of digoxin was significantly associated with increased risk of SCD (p-value 0.0001). In model 2, the risk of SCD in current users of digoxin was 4.2 [95% CI 1.3–13.8] for the GG genotype; 2.1 [95% CI 1.1–4.2] for the GT genotype, and 1.5 [95% CI 0.7–3.2] for the TT genotype. Conclusion NOS1AP rs10494366 variant modified the risk of sudden cardiac death in users of digoxin. Our study suggests that individuals with the homozygous minor GG allele have a fourfold increased risk of sudden cardiac death. Funding Acknowledgement Type of funding source: None

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N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy

Heart ◽

10.1136/heartjnl-2020-317701 ◽

2020 ◽

pp. heartjnl-2020-317701

Author(s):

Guixin Wu ◽

Jie Liu ◽

Shuiyun Wang ◽

Shiqin Yu ◽

Ce Zhang ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Cardiac Death ◽

Cardiac Fibrosis ◽

Discrimination Performance ◽

Net Reclassification Improvement ◽

C Statistic ◽

Increased Risk

ObjectiveElevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.MethodsThe study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell’s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson’s staining was analysed.ResultsDuring follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson’s trichrome staining in the myocardium (r=0.198, p<0.05).ConclusionNT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

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DNA methylation is associated with airflow obstruction in patients living with HIV

Thorax ◽

10.1136/thoraxjnl-2020-215866 ◽

2020 ◽

pp. thoraxjnl-2020-215866

Author(s):

Ana I Hernandez Cordero ◽

Chen Xi Yang ◽

Maen Obeidat ◽

Julia Yang ◽

Julie MacIsaac ◽

...

Keyword(s):

Dna Methylation ◽

Lung Function ◽

Viral Infections ◽

Airflow Obstruction ◽

Normal Lung ◽

People Living With Hiv ◽

Global Methylation ◽

Age Related ◽

Impaired Lung Function ◽

Living With Hiv

IntroductionPeople living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH.MethodsUsing blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV1, FEV1/FVC ratio and FEV1 decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing.ResultsAirflow obstruction as defined by a FEV1/FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV1/FVC<lower limit of normal. These DMPs were enriched for biological pathways associated with chronic viral infections. The airflow obstruction group was globally hypomethylated compared with those without airflow obstruction. 103 and 7112 DMPs were associated with FEV1 and FEV1/FVC, respectively. No positions were associated with FEV1 decline.ConclusionA large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.

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Household Food Insecurity, Lung Function, and COPD in US Adults

Nutrients ◽

10.3390/nu13062098 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2098

Author(s):

Francisca de Castro Mendes ◽

Kirstie Ducharme-Smith ◽

Gustavo Mora-Garcia ◽

Saleh A. Alqahtani ◽

Maria Stephany Ruiz-Diaz ◽

...

Keyword(s):

Lung Function ◽

Food Insecurity ◽

Representative Sample ◽

Airflow Obstruction ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

The Us ◽

Nationally Representative ◽

Lung Health

Increasing epidemiological evidence suggests that optimal diet quality helps to improve preservation of lung function and to reduce chronic obstructive pulmonary disease (COPD) risk, but no study has investigated the association of food insecurity (FI) and lung health in the general population. Using data from a representative sample of US adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012 cycles, we investigated the association between FI with lung function and spirometrically defined COPD in 12,469 individuals aged ≥ 18 years of age. FI (high vs. low) was defined using the US Department of Agriculture’s Food Security Scale). Population-weighted adjusted regression models were used to investigate associations between FI, and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio, and spirometrically defined restriction (FVC below the lower limit of normal) and airflow obstruction (COPD). The prevalence of household FI was 13.2%. High household FI was associated with lower FVC (adjusted β-coefficient −70.9 mL, 95% CI −116.6, −25.3), and with higher odds (OR) of spirometric restriction (1.02, 95% CI 1.00, 1.03). Stratified analyses showed similar effect sizes within specific ethnic groups. High FI was associated with worse lung health in a nationally representative sample of adults in the US.

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Prevalence and burden of chronic bronchitis symptoms: results from the BOLD study

European Respiratory Journal ◽

10.1183/13993003.00621-2017 ◽

2017 ◽

Vol 50 (5) ◽

pp. 1700621 ◽

Cited By ~ 19

Author(s):

Filip Mejza ◽

Louisa Gnatiuc ◽

A. Sonia Buist ◽

William M. Vollmer ◽

Bernd Lamprecht ◽

...

Keyword(s):

Lung Function ◽

Lung Disease ◽

Chronic Bronchitis ◽

Airflow Obstruction ◽

Population Based ◽

Normal Lung ◽

Increased Risk ◽

Potential Risk Factors ◽

Definition Of ◽

Disease Study

We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.Representative population-based samples of adults aged ≥40 years were selected in participating sites. Participants completed questionnaires and spirometry. Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.Data from 24 855 subjects from 33 sites in 29 countries were analysed. There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi). Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis. Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.The prevalence of chronic bronchitis symptoms varied widely across the studied sites. Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.

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Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study

Heart ◽

10.1136/heartjnl-2017-311825 ◽

2017 ◽

Vol 104 (5) ◽

pp. 423-429 ◽

Cited By ~ 2

Author(s):

Brittany M Bogle ◽

Nona Sotoodehnia ◽

Anna M Kucharska-Newton ◽

Wayne D Rosamond

Keyword(s):

Risk Factors ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Disease Risk ◽

Ventricular Tachyarrhythmia ◽

Atherosclerosis Risk In Communities ◽

Vital Exhaustion ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

ObjectiveVital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsThe ARIC Study is a predominately biracial cohort of men and women, aged 45–64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores.ResultsThrough 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20).ConclusionsAmong participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.

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Abstract 2415: Long-Term Baroreflex Activation Therapy Increases the Threshold for the Induction of Lethal Ventricular Arrhythmias in Dogs with Chronic Advanced Heart Failure

Circulation ◽

10.1161/circ.118.suppl_18.s_722 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Mengjun Wang ◽

Valerio Zaca ◽

Alice Jiang ◽

Itamar Ilsar ◽

Matthew Ebinger ◽

...

Keyword(s):

Heart Failure ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Ventricular Arrhythmias ◽

Lv Function ◽

Baroreflex Activation Therapy ◽

Increased Risk ◽

Lv Remodeling ◽

Activation Therapy

Heart failure (HF) is associated with a high incidence of ventricular tachycardia (VT) and fibrillation (VF). Patients with HF in whom these lethal arrhythmias can be induced by electrophysiological (EP) testing carry a high risk of sudden cardiac death. We showed that chronic electrical carotid baroreflex activation therapy (BAT) with the Rheos® System (CVRx, Inc.) improves LV function, attenuates LV remodeling and restores autonomic sympathetic-parasympathetic balance in dogs with HF. This study examined the effects of long-term therapy with BAT on the induction of VT or VF in dogs with coronary microembolization-induced HF (LV ejection fraction ~20%). Eleven dogs with HF underwent EP testing at baseline prior to therapy and after 3 and 6 months of therapy with BAT and again 6 weeks after withdrawal of BAT therapy (n = 7) or no therapy at all (Control, n = 4). Programmed ventricular stimulation was performed from the right ventricular apex and included delivery of up to 4 extrastimuli at progressively shorter coupling intervals (in steps of 10 msec). The extrastimuli were delivered following 8 ventricular paced beats with a drive cycle length between 600 and 200 msec. If a sustained monomorphic VT or VF could not be induced, isoproterenol infusion was initiated to increase the sinus rate by ~30% and the EP stimulation protocol was repeated. At baseline, a sustained VT or VF was induced in all 11 dogs (100%). After 3 and 6 months of follow-up, all Control dogs (100%) were induced into sustained VT or VF. After 3 months of BAT, only 3 of 7 dogs (43%) were induced into sustained VT or VF. After 6 months of BAT, only 2 of 7 dogs (29%) were induced into sustained VT or VF. Finally after withdrawal of BAT therapy, all dogs (100%) were again induced into systained VT or VF. In addition to improving LV function and attenuating LV remodeling, long-term monotherapy with BAT markedly increases the threshold for lethal ventricular arrhythmias in dogs with chronic HF. This is a marked improvement over inducibility of lethal arrhythmias seen in historical untreated controls. This benefit of BAT supports the continued exploration of this device as a therapeutic modality for treating patients with chronic HF and increased risk of sudden cardiac death.

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Persistent airflow obstruction in inner-city children with asthma

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.210043 ◽

2021 ◽

Vol 42 (4) ◽

pp. 310-316

Author(s):

Kenny Y. Kwong ◽

Yang Z. Lu ◽

Emilio Jauregui ◽

Lyne Scott

Keyword(s):

Lung Function ◽

Inner City ◽

Airway Remodeling ◽

Airflow Obstruction ◽

Later Life ◽

Forced Expiratory Volume ◽

Initial Visit ◽

Asthma Care ◽

Increased Risk ◽

Children With Asthma

Background: Airway remodeling has been shown to be persistent in patients with asthma despite treatment with controller medications. Patients with early airflow obstruction may continue to experience poor lung function despite treatment. Objectives: To determine whether early airflow obstruction in inner-city children with asthma persists despite guideline-based asthma care. Methods: In a retrospective study that used a cohort of inner-city children with asthma treated by using an asthma-specific disease management system, the patients were stratified into “low” or “high” lung function groups at the time of the initial visit (high, forced expiratory volume in the first second of expiration [FEV1] % predicted and FEV1/forced vital capacity [FVC] ≥ 80%; and low, FEV1% predicted and FEV1/FVC < 80%). These patients then received National Heart, Lung, and Blood Institute guideline‐based asthma treatment at regular follow-up intervals with spirometry performed at these visits as part of regular care. FEV1% predicted and FEV1/FVC were followed up for up to 10 years for both the high and low cohorts. Results: Over 10 years, the patients initially in the “high” group maintained FEV1% predicted and FEV1/FVC at values similar to the initial visit (94 to 96% and 87 to 89%, respectively), whereas those in the low group had only slight increases of FEV1% predicted and FEV1/FVC over the same time (77 to 82% and 78 to 82%, respectively). Low FEV1% predicted and FEV1/FVC at the time of the first visit was significantly associated with an increased risk of low values of these lung functions over the next 3‐5 years despite treatment. African American ethnicity and male gender were also associated with lower lung function over time. Conclusion: Early airflow obstruction in inner city children asthma is associated with poor lung function in later life despite guideline-based asthma care. Current asthma therapy may not affect pathways and leads to airway remodeling in children with asthma.

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Abstract 14760: Myocardial Scarring by Magnetic Resonance Predicts Sudden Cardiac Death in Pediatric Patients With Hypertrophic Cardiomyopathy

Circulation ◽

10.1161/circ.142.suppl_3.14760 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Lars Grosse-Wortmann ◽

Laurine van der Wal ◽

Aswathy Vaikom House ◽

Lee Benson ◽

Raymond Chan

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Pediatric Patients ◽

Risk Markers ◽

C Statistic ◽

Increased Risk ◽

Traditional Risk Factors

Introduction: Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) has been shown to be an independent predictor of sudden cardiac death (SCD) in adults with hypertrophic cardiomyopathy (HCM). The clinical significance of LGE in pediatric HCM patients is unknown. Hypothesis: LGE improves the SCD risk prediction in children with HCM. Methods: We retrospectively analyzed the CMR images and reviewed the outcomes pediatric HCM patients. Results: Amongst the 720 patients from 30 centers, 73% were male, with a mean age of 14.2±4.8 years. During a mean follow up of 2.6±2.7 years (range 0-14.8 years), 34 experienced an episode of SCD or equivalent. LGE (Figure 1A) was present in 34%, with a mean burden of 14±21g, or 2.5±8.2g/m2 (6.2±7.7% of LV myocardium). The presence of ≥1 adult traditional risk factor (family history of SCD, syncope, LV thickness >30mm, non-sustained ventricular tachycardia on Holter) was associated with an increased risk of SCD (HR=4.6, p<0.0001). The HCM Risk-Kids score predicted SCD (p=0.002). The presence of LGE was strongly associated with an increased risk (HR=3.8, p=0.0003), even after adjusting for traditional risk factors (HR adj =3.2, p=0.003) or the HCM Risk-Kids score (HR adj =3.5, p=0.003). Furthermore, the burden of LGE was associated with increased risk (HR=2.1/10% LGE, p<0.0001). LGE burden remained independently associated with an increased risk for SCD after adjusting for traditional risk factors (HRadj=1.5/10% LGE, p=0.04) or HCM Risk-Kids (HRadj=1.9/10% LGE, p=0.0018, Figure 1B). The addition of LGE burden improved the predictive model using traditional risk markers (C statistic 0.67 vs 0.77, p=0.003) and HCM Risk-Kids (C statistic 0.68 vs 0.74, p=0.045). Conclusions: Quantitative LGE is an independent risk factor for SCD in pediatric patients with HCM and improves the performance of traditional risk markers and the HCM Risk-Kids Score for SCD risk stratification in this population.

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