title: Prediction of Future Overt Pulmonary Hypertension by 6-Min Walk Stress Echocardiography in Patients With Connective Tissue Disease.
abstract: BACKGROUND
  Early detection of pulmonary hypertension (PH) in connective tissue disease (CTD) is crucial to ensuring that patients receive timely treatment for this progressive disease. Exercise stress tests have been used to screen patients in an attempt to identify early-stage PH. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (Q) responses as having the potential to assess the disease state.
  
  
  OBJECTIVE
  This study hypothesized that pulmonary circulation pressure-flow relationships obtained by 6-min walk (6MW) stress echocardiography would better delineate differential progression of PH and predict development of PH during follow-up.
  
  
  METHODS
  We prospectively performed 6MW stress echocardiographic studies in 78 CTD patients (age 58 ± 12 years; 9% male) at baseline and follow-up. All patients underwent yearly echocardiographic follow-up studies for up to 5 years.
  
  
  RESULTS
  During a median period of 32 months (range: 15 to 62 months), 16 patients reached the clinical endpoint of development of PH and none died during follow-up. PH was confirmed by right heart catheterization in all 16 patients (mPAP ≥25 mm Hg and pulmonary capillary wedge pressure ≤15 mm Hg). In a Cox proportional-hazards survival model, 6MW distance (hazard ratio [HR]: 0.99; p = 0.010), early diastolic tricuspid annulus motion velocity (HR: 0.79; p = 0.025), and ΔmPAP/ΔQ by 6MW stress (HR: 1.10; p = 0.005) were associated with development of PH. In sequential Cox models, a model on the basis of 6MW distance (chi-square, 6.6) was improved by ΔmPAP/ΔQ (chi-square: 14.4; p = 0.019). Using a receiver-operating characteristic curve, we found that the best cutoff value of ΔmPAP/ΔQ for predicting development of pulmonary hypertension was >3.3 mm Hg/l/min.
  
  
  CONCLUSIONS
  The 6MW stress echocardiography noninvasively provides an incremental prognostic value of PH development in CTD. This is a single-center prospective cohort study. Larger multicenter studies are warranted to confirm this result.
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kusunose
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan. Electronic address: yamadah@tokushima-u.ac.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hotchi
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Bando
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nishio
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Yukina
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ise
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yagi
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Wakatsuki
authors.affiliation: Department of Respiratory Medicine & Rheumatology, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kishi
authors.affiliation: Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D000368:Aged; D002302:Cardiac Output; D003240:Connective Tissue Diseases / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D025401:Echocardiography, Stress; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure; D012372:ROC Curve; D016138:Walking / Q000502:physiology
keywords: lupus erythematosus; mixed connective tissue disease; pulmonary circulation; systemic scleroderma