title: Increased ventilatory response to exercise in symptomatic and asymptomatic LMNA mutation carriers: a follow-up study.
abstract: BACKGROUND
  LMNA mutations are an important cause of cardiomyopathy often leading to cardiac arrhythmias, heart failure and even heart transplantation. An increasing number of asymptomatic mutation carriers are identified, as family members of the index patients are screened. Our aim was to study the disease progression in asymptomatic LMNA mutation carriers and in patients with symptomatic cardiolaminopathy by repeated spiroergometric testing in a prospective clinical follow-up study.
  
  
  RESULTS
  We studied 26 LMNA mutation carriers once a year during 5 years up to 6 times by spiroergometry, clinical assessment, laboratory tests and echocardiography. The 23 control subjects underwent clinical assessment and spiroergometry once. Twelve of the mutation carriers were asymptomatic, and 14 had some clinical manifestations of the mutation ranging from clinically relevant rhythm disturbances to DCM and heart failure. Compared to controls, the symptomatic carriers showed a higher slope of the ventilatory equivalent for CO2(V˙E/V˙CO2slope) and a lower fraction of end-tidal CO2(FetCO2). The asymptomatic mutation carriers also showed an increased ventilatory response to exercise during the follow-up as indicated by increased V˙E/V˙CO2slope and decreased FetCO2.
  
  
  CONCLUSIONS
  The study suggests that an increased ventilatory response during exercise might reveal a preclinical manifestation of DCM in LMNA mutation carriers.
authors.affiliation: Heart and Lung Centre, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Ollila
authors.affiliation: Heart and Lung Centre, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Heliö
authors.affiliation: Unit of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Anssi
authors.initials: A
authors.lastname: Sovijärvi
authors.affiliation: Heart and Lung Centre, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Jalanko
authors.affiliation: Heart and Lung Centre, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Maija
authors.initials: M
authors.lastname: Kaartinen
authors.affiliation: University of Eastern Finland, Kuopio, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.affiliation: University of Eastern Finland, Kuopio, Finland.|Heart Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Kärkkäinen
authors.affiliation: Heart and Lung Centre, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Jurkko
authors.affiliation: Heart and Lung Centre, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Reissell
authors.affiliation: Heart and Lung Centre, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Palojoki
authors.affiliation: Unit of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Piirilä
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D018450:Disease Progression; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010101:Oxygen Consumption; D010641:Phenotype; D011446:Prospective Studies; D012123:Pulmonary Ventilation; D013147:Spirometry; D055815:Young Adult
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A
keywords: FetCO2; V˙E/V˙CO2 slope; cardiomyopathy; clinical exercise testing; spiroergometry