title: Value of Genetic Testing for the Prediction of Long-Term Outcome in Patients With Hypertrophic Cardiomyopathy.
abstract: Pathogenic gene mutations are found in about 50% of patients with hypertrophic cardiomyopathy (HC). Previous studies have shown an association between sarcomere mutations and medium-term outcome. The association with long-term outcome has not been described. The aim of this cohort study was to assess the long-term outcomes of patients with genotype positive (G+) and genotype negative (G-) HC. The study population consisted of 626 patients with HC (512 probands and 114 relatives) who underwent phenotyping and genetic testing from 1985 to 2014. End points were all-cause mortality, cardiovascular (CV) mortality, heart failure (HF)-related mortality, and sudden cardiac death/aborted sudden cardiac death (SCD/aborted SCD). Kaplan-Meier and multivariate Cox regression analyses were performed. A pathogenic mutation was detected in 327 patients (52%). G+ probands were younger than G- probands (46 ± 15 vs 55 ± 15 years, p <0.001), had more non sustained ventricular tachycardia (34% vs 13%; p <0.001), more often a history of syncope (14% vs 7%; p = 0.016), and more extreme hypertrophy (maximal wall thickness ≥30 mm, 7% vs 1%; p <0.001). G- probands were more symptomatic (New York Heart Association ≥II, 73% vs 53%, p <0.001) and had higher left ventricular outflow tract gradients (42 ± 39 vs 29 ± 33 mm Hg, p = 0.001). During 12 ± 9 years of follow-up, G+ status was an independent risk factor for all-cause mortality (hazard ratio [HR] 1.90, 95% CI 1.14 to 3.15; p = 0.014), CV mortality (HR 2.82, 95% CI 1.49 to 5.36; p = 0.002), HF-related mortality (HR 6.33, 95% CI 1.79 to 22.41; p = 0.004), and SCD/aborted SCD (HR 2.88, 95% CI 1.23 to 6.71; p = 0.015). In conclusion, during long-term follow-up, patients with G+ HC are at increased risk of all-cause death, CV death, HF-related death, and SCD/aborted SCD.
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: h.g.vanvelzen@erasmusmc.nl.
authors.forename: Hannah G
authors.initials: HG
authors.lastname: van Velzen
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Vriesendorp
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Rogier A
authors.initials: RA
authors.lastname: Oldenburg
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marjon A
authors.initials: MA
authors.lastname: van Slegtenhorst
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Arend F L
authors.initials: AFL
authors.lastname: Schinkel
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Michelle
authors.initials: M
authors.lastname: Michels
mesh_terms: D000328:Adult; D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000401:mortality; D002318:Cardiovascular Diseases / Q000401:mortality; D002352:Carrier Proteins / Q000235:genetics; D002423:Cause of Death; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D005820:Genetic Testing; D005838:Genotype; D006333:Heart Failure / Q000401:mortality*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D018995:Myosin Heavy Chains / Q000235:genetics; D018994:Myosin Light Chains / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D018994:Myosin Light Chains; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human; C000609827:myosin light chain 3, human