title: Evaluation of the Incremental Prognostic Utility of Increasingly Complex Testing in Chronic Heart Failure.
abstract: BACKGROUND
  Current heart failure (HF) risk prediction models do not consider how individual patient assessments occur in incremental steps; furthermore, each additional diagnostic evaluation may add cost, complexity, and potential morbidity.
  
  
  RESULTS
  Using a cohort of well-treated ambulatory HF patients with reduced ejection fraction who had complete clinical, laboratory, health-related quality of life, imaging, and exercise testing data, we estimated incremental prognostic information provided by 5 assessment categories, performing an additional analysis on those with available N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. We compared the incremental value of each additional assessment (quality of life screen, laboratory testing, echocardiography, and exercise testing) to baseline clinical assessment for predicting clinical outcomes (all-cause mortality, all-cause mortality/hospitalization, and cardiovascular death/HF hospitalizations), gauging incremental improvements in prognostic ability with more information using area under the curve and reclassification improvement (net reclassification index), with and without NT-proBNP availability. Of 2331 participants, 1631 patients had complete clinical data; of these, 1023 had baseline NT-proBNP. For prediction of all-cause mortality, models with incremental assessments sans NT-proBNP showed improvements in C-indices (0.72 [clinical model alone]-0.77 [complete model]). Compared with baseline clinical assessment alone, net reclassification index improved from 0.035 (w/laboratory data) to 0.085 (complete model). These improvements were significantly attenuated for models in the subset with measured NT-proBNP data (c-indices: 0.80 [w/laboratory data]-0.81 [full model]); net reclassification index improvements were similarly marginal (0.091→0.096); prediction of other clinical outcomes had similar findings.
  
  
  CONCLUSIONS
  In chronic HF patients with reduced ejection fraction, the marginal benefit of complex prognostic evaluations should be weighed against potential patient discomfort and cost escalation.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Emily C
authors.initials: EC
authors.lastname: O'Brien
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Schulte
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Dalane W
authors.initials: DW
authors.lastname: Kitzman
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Piña
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Mark P
authors.initials: MP
authors.lastname: Donahue
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.).
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: From the Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (T.A.); Duke Clinical Research Institute, Durham, NC (E.C.O., P.J.S., S.R.S., M.F., C.M.O., G.M.F.); Division of Cardiology, Duke University Medical Center, Durham, NC (M.F., W.E.K., M.P.D., G.M.F.); Department of Cardiology, Wake Forest University, Winston-Salem, NC (D.W.K.); Department of Cardiology, University of North Carolina, Chapel Hill (K.F.A.); Montefiore Medical Center, Bronx, NY (I.L.P.); Department of Cardiology, Nancy University, Nancy, France (F.Z.); Department of Cardiology, Thomas Jefferson University, Philadelphia, PA (D.J.W.); and Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.). michael.felker@duke.edu.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D002908:Chronic Disease; D003935:Diagnostic Techniques, Cardiovascular; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology / Q000523:psychology / Q000628:therapy; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011788:Quality of Life; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume; D011795:Surveys and Questionnaires; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: echocardiography; heart failure; hospitalization; natriuretic peptide, brain; quality of life