Tracking of structural and functional cardiac measures from infancy into school-age

Objective Cardiac structure and function are important predictors for cardiovascular disease in adults. Not much is known about tracking of cardiac measures, other than left ventricular mass, from early life onwards. We examined whether and to what extent cardiac measures track from infancy into school-age. Methods We performed a population-based prospective cohort study among 1072 children. Aortic root diameter, left atrial diameter, left ventricular mass, relative wall thickness and fractional shortening were measured repeatedly by echocardiography. We explored tracking between infancy (1.5, six and 24 months) and school-age (six and 10 years). Results Of all cardiac measures, aortic root diameter, left atrial diameter and left ventricular mass were significantly correlated between infancy and school-age (r = 0.10-0.42, all p-values < 0.01), with the strongest correlations between 24 months and 10 years. Of the different structures, aortic root diameter showed the strongest correlations. Approximately 30% of children who were in the lowest or highest quartile of a measure at the age of 1.5 months remained in that quartile at the age of 10 years. When analysing the effects of the infant cardiac measures on the same outcomes at 10 years in conditional regression models, we observed ef

Cardiac allograft vasculopathy and donor age affecting permanent pacemaker implantation after heart transplantation

AIMS: The need for permanent pacemakers (PMs) after heart transplantation (HT) is increasing. The aim was to determine the influence of cardiac allograft vasculopathy (CAV), donor age, and other risk factors on PM implantations early and late after HT and its effect on survival. METHODS AND RESULTS: A retrospective, single‐centre study was performed including HTs from 1984 to July 2018. Early PM was defined as PM implantation ≤90 days and late PM as PM > 90 days. Risk factors for PM and survival after PM were determined with (time‐dependent) multivariable Cox regression. Out of 720 HTs performed, 62 were excluded (55 mortalities ≤30 days and 7 retransplantations). Of the remaining 658 patients, 95 (14%) needed a PM: 38 (6%) early and 57 (9%) late during follow‐up (median 9.3 years). Early PM risk factors were donor age [hazard ratio (HR) 1.06, P < 0.001], ischaemic time (HR 1.01, P < 0.001), and in adults amiodarone use before HT (HR 2.02, P = 0.045). Late PM risk factors were donor age (HR 1.03, P = 0.024) and CAV (HR 3.59, P < 0.001). Late PM compromised survival (HR 2.05, P < 0.001), while early PM did not (HR 0.77, P = 0.41). CONCLUSIONS: Risk factors for early PM implantation were donor age, ischaemic time, and in adults amiodarone use before HT. Late PM implantation risk factors were donor age and CAV. Late PM diminished survival, which is probably a surrogate marker for underlying progressive cardiac disease

Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants

Introduction: Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined. Methods and Results: We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense variants, and one homozygous deleterious missense variant were identified. Among 18 live-born patients, 8 exhibited neonatal dilated cardiomyopathy (44.4%; 95% CI: 21.5%-69.2%) that subsequently transitioned into ventricular hypertrophy. The majority of patients had extracardiac phenotypes, including contractures, scoliosis, cleft palate, and facial dysmorphisms. We observed no association between variant type or location, disease severity, and/or extracardiac manifestations. Myocardial histopathology showed focal cardiomyocyte hypertrophy, subendocardial fibroelastosis in patients under 4 years of age, and myofibrillar disarray in adults. Rare heterozygous ALPK3 variants were also assessed in adult-onset cardiomyopathy patients. Among 1548 Dutch patients referred for initial genetic analyses, we identified 39 individuals with rare heterozygous ALPK3 variants (2.5%; 95% CI: 1.8%-3.4%), including 26 missense and 10 LoF variants. Among 149 U.S. patients without pathogenic variants in 83 cardiomyopathy-related genes, we identified six missense and nine LoF ALPK3 variants (10.1%; 95% CI: 5.7%-16.1%). LoF ALPK3 variants were increased in comparison to matched controls (Dutch cohort, P = 1.6×10−5; U.S. cohort, P = 2.2×10−13). Conclusion: Biallelic damaging ALPK3 variants cause pediatric cardiomyopathy manifested by DCM transitioning to hypertrophy, often with poor contractile function. Additional extracardiac features occur in most patients, including musculoskeletal abnormalities and cleft palate. Heterozygous LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. Adults with ALPK3 LoF variants therefore warrant evaluations for cardiomyopathy

Maternal educational level and blood pressure, aortic stiffness, cardiovascular structure and functioning in childhood

background In adults, low level of education was shown to be associated with higher blood pressure levels and alterations in cardiac structures and function. It is currently unknown whether socioeconomic inequalities in arterial and cardiac alterations originate in childhood. Therefore, we investigated the association of mat