Predicting sudden cardiac death in adults with congenital heart disease.

OBJECTIVES: To develop, calibrate, test and validate a logistic regression model for accurate risk prediction of sudden cardiac death (SCD) and non-fatal sudden cardiac arrest (SCA) in adults with congenital heart disease (ACHD), based on baseline lesion-specific risk stratification and individual's characteristics, to guide primary prevention strategies. METHODS: We combined data from a single-centre cohort of 3311 consecutive ACHD patients (50% male) at 25-year follow-up with 71 events (53 SCD and 18 non-fatal SCA) and a multicentre case-control group with 207 cases (110 SCD and 97 non-fatal SCA) and 2287 consecutive controls (50% males). Cumulative incidences of events up to 20 years for specific lesions were determined in the prospective cohort. Risk model and its 5-year risk predictions were derived by logistic regression modelling, using separate development (18 centres: 144 cases and 1501 controls) and validation (two centres: 63 cases and 786 controls) datasets. RESULTS: According to the combined SCD/SCA cumulative 20 years incidence, a lesion-specific stratification into four clusters-very-low (<1%), low (1%-4%), moderate (4%-12%) and high (>12%)-was built. Multivariable predictors were lesion-specific cluster, young age, male sex, unexplained syncope, ischaemic heart disease, non-life threatening ventricular arrhythmias, QRS duration and ventricular systolic dysfunction or hypertrophy. The model very accurately discriminated (C-index 0.91; 95% CI 0.88 to 0.94) and calibrated (p=0.3 for observed vs expected proportions) in the validation dataset. Compared with current guidelines approach, sensitivity increases 29% with less than 1% change in specificity. CONCLUSIONS: Predicting the risk of SCD/SCA in ACHD can be significantly improved using a baseline lesion-specific stratification and simple clinical variables.

Impact of age and sex on survival and causes of death in adults with congenital heart disease.

BACKGROUND: The impact of gender and aging on relative survival and causes of death in adults with congenital heart disease (ACHD) are not well known. METHODS: Single center observational longitudinal study of 3311 consecutive ACHD (50.5% males) followed up to 25years. Patients were divided by the age at last follow-up into three groups: <40, 40-65 and >65years old. Their vital status was verified by crosschecking the Spanish National Death Index. Regression model for relative survival from reference population was performed. Cause of death was classified according to the International Classification of Diseases (ICD-10). Patients who died from cardiovascular (CV) causes were further investigated on a case-by-case basis. RESULTS: During a cumulative follow-up time of 37,608 person-years 336 patients died (10%). Age-adjusted relative survival in females was significantly worse than in males (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.0-1.6; p=0.046), and sex-adjusted relative survival improved across the three group of ages (HR 0.98; 95% CI 0.97-0.99; p<0.001). There was a temporal decline of CV deaths with aging in both genders (p<0.001). The leading cause of CV death was heart failure but sudden death prevailed in subjects <40years (p=0.004). While sudden death progressively declined with aging heart failure significantly increased (p<0.001). CONCLUSIONS: Women with CHD fare worse than men. There are a decline in CV deaths and a major temporal shift in the causes of CV deaths with aging. Heart failure surpasses sudden death as the primary cause of death in survivors over 40years.

Risk factors for excess mortality in adults with congenital heart diseases.

AIMS: To examine factors related to excess mortality in a cohort of adults with congenital heart disease (CHD). METHODS AND RESULTS: We conducted a survival analysis using prospective data of 3311 adults with CHD [50.5% males, median age at entry 22.5 years (IQR 18-39), median follow-up time 10.5 years (IQR: 4.4-18)]. Survival status of each patient was further verified by cross checking with the Spanish National Death Index. During a total follow-up of 37608 person-years, 336 (10%) patients died. Annual death rate was 0.89% and standardized mortality ratio (SMR) 2.64 [95% confidence interval (CI) 2.3-3.0; P < 0.001]. Median age at death estimated by left-truncated Kaplan-Meier method was 75.1 years (95% CI 73-77). Survival was reduced compared with the general population whatever their level of complexity, repair status, or underlying CHD. Independent risk factors for excess mortality, including cyanosis, univentricular physiology, genetic disorders, ventricular dysfunction, residual haemodynamic lesions and acquired late complications, among others, were identified by left-truncated Cox regression model. SMR was 5.22 (95% CI 4.5-6.0; P < 0.001) and median age at death 55.6 years (95% CI 50-61) for 996 patients (30%) with at least one risk factor. In contrast, SMR was 1.14 (95% CI 0.9-1.5; P = 0.19) and median age at death 83.7 years (95% CI 82-87) in 2315 patients (70%) with no risk factors. CONCLUSIONS: Clinical parameters, such as anatomical features, haemodynamic sequelae, or acquired complications, were independent predictors of excess mortality in adults with CHD. Survival of individuals with no risk factors did not differ from the reference population.

Risk Factors for Prosthetic Pulmonary Valve Failure in Patients With Congenital Heart Disease.

The incidence and risk factors for prosthetic pulmonary valve failure (PPVF) should be considered when determining optimal timing for pulmonary valve replacement (PVR) in asymptomatic patients with congenital heart disease (CHD). The cumulative freedom for reintervention due to PPVF after 146 PVR in 114 patients with CHD was analyzed. Six potential risk factors (underlying cardiac defect, history of palliative procedures, number of previous cardiac interventions, hemodynamic indication for PVR, type of intervention, and age at intervention) were analyzed using Cox proportional hazard modeling. Receiver operating characteristic (ROC) curves were used for discrimination. Internal validation in patients with tetralogy of Fallot was also performed. Median age at intervention was 23 years. There were 60 reinterventions due to PPVF (41%). Median event-free survival was 14 years (95% confidence interval [CI] 12 to 16 years). The only independent risk factor was the age at intervention (hazard ratio [HR] 0.93, 95% CI 0.90 to 0.97; p = 0.001; area under the ROC curve 0.95, 95% CI 0.92 to 0.98; p <0.001). The best cut-off point was 20.5 years. Freedom from reintervention for PPVF 15 years after surgery was 70% when it was performed at age >20.5 years compared with 33% when age at intervention was <20.5 years (p = 0.004). Internal validation in 102 PVR in patient cohort with tetralogy of Fallot (ROC area 0.98, 95% CI 0.96 to 1.0; p <0.001) was excellent. In conclusion, age at intervention is the main risk factor of reintervention for PPVF. The risk of reintervention is 2-fold when PVR is performed before the age of 20.5 years.