Prevalence of transthyretin cardiac amyloidosis in patients with high-degree AV block.

OBJECTIVE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative cardiac disorder caused by deposition of wild type or mutated transthyretin. As ATTR-CM is associated with conduction disease, we sought to determine its prevalence in patients with idiopathic high-degree atrioventricular (AV) block requiring permanent pacemaker (PPM) implantation. METHODS: Consecutive patients aged 70-85 years undergoing PPM implantation for idiopathic high-degree AV block between November 2019 and November 2021 were offered a 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan. Demographics, comorbidities, electrocardiographic and imaging data from the time of device implantation were retrospectively collected. RESULTS: 39 patients (79.5% male, mean (SD) age at device implantation 76.2 (2.9) years) had a DPD scan. 3/39 (7.7%, all male) had a result consistent with ATTR-CM (Perugini grade 2 or 3). Mean (SD) maximum wall thickness of those with a positive DPD scan was 19.0 mm (3.6 mm) vs 11.4 mm (2.7 mm) in those with a negative scan (p=0.06). All patients diagnosed with ATTR-CM had spinal canal stenosis and two had carpal tunnel syndrome. CONCLUSIONS: ATTR-CM should be considered in older patients requiring permanent pacing for high-degree AV block, particularly in the presence of left ventricular hypertrophy, carpal tunnel syndrome or spinal canal stenosis.

Novel Multiplexed Plasma Biomarker Panel Has Diagnostic and Prognostic Potential in Children With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is defined clinically by pathological left ventricular hypertrophy. We have previously developed a plasma proteomics biomarker panel that correlates with clinical markers of disease severity and sudden cardiac death risk in adult patients with HCM. The aim of this study was to investigate the utility of adult biomarkers and perform new discoveries in proteomics for childhood-onset HCM. METHODS: Fifty-nine protein biomarkers were identified from an exploratory plasma proteomics screen in children with HCM and augmented into our existing multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay. The association of these biomarkers with clinical phenotypes and outcomes was prospectively tested in plasma collected from 148 children with HCM and 50 healthy controls. Machine learning techniques were used to develop novel pediatric plasma proteomic biomarker panels. RESULTS: Four previously identified adult HCM markers (aldolase fructose-bisphosphate A, complement C3a, talin-1, and thrombospondin 1) and 3 new markers (glycogen phosphorylase B, lipoprotein a and profilin 1) were elevated in pediatric HCM. Using supervised machine learning applied to training (n=137) and validation cohorts (n=61), this 7-biomarker panel differentiated HCM from healthy controls with an area under the curve of 1.0 in the training data set (sensitivity 100% [95% CI, 95-100]; specificity 100% [95% CI, 96-100]) and 0.82 in the validation data set (sensitivity 75% [95% CI, 59-86]; specificity 88% [95% CI, 75-94]). Reduced circulating levels of 4 other peptides (apolipoprotein L1, complement 5b, immunoglobulin heavy constant epsilon, and serum amyloid A4) found in children with high sudden cardiac death risk provided complete separation from the low and intermediate risk groups and predicted mortality and adverse arrhythmic outcomes (hazard ratio, 2.04 [95% CI, 1.0-4.2]; P=0.044). CONCLUSIONS: In children, a 7-biomarker proteomics panel can distinguish HCM from controls with high sensitivity and specificity, and another 4-biomarker panel identifies those at high risk of adverse arrhythmic outcomes, including sudden cardiac death.