Advertisement

Clinical exacerbations as a surrogate end point in heart failure research

      Background

      We examined the utility of an index of clinical exacerbations of heart failure (HF) as a surrogate measure of outcome for use in modestly sized clinical trials and observational studies.

      Methods

      Electronic records of 189 outpatients with HF in a US Veterans Affairs Medical Center were examined over a 2- to 3-year period. Data collected included patient characteristics, clinical exacerbations of HF, hospitalizations, and deaths. Subsets of patient were also assessed for HF-related level of functioning.

      Results

      Episodes of clinical exacerbation could be detected reliably (kappa = .83). An index of episodes (number of episodes divided by the time in years) was associated with lower quality of life, higher functional class, increased rate of HF hospitalization, poorer exercise tolerance, and up to 30% increased risk of mortality across 2 years.

      Conclusions

      The index of HF exacerbations is potentially a useful surrogate end point for use in clinical HF research.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Heart & Lung: The Journal of Cardiopulmonary and Acute Care
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • National Heart Lung and Blood Institute. (US Dept of Health and Human Services)
        Congestive Heart Failure in the United States: A New Epidemic.
        1996 (Bethesda, MD)
        • Anand I.S.
        • Florea V.G.
        • Fisher L.
        Surrogate end points in heart failure.
        J Am Coll Cardiol. 2002; 39: 1414-1421
        • Zanolla L.
        • Zardini P.
        Selection of endpoints for heart failure clinical trials.
        Eur J Heart Fail. 2003; 5: 717-723
        • Lucas C.
        • Johnson W.
        • Hamilton M.A.
        • et al.
        Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure.
        Am Heart J. 2000; 140: 840-847
        • Torosoff M.
        • Sullivan B.P.
        • Fein S.A.
        • et al.
        Determinants of long-term survival in patients with congestive heart failure: the independent prognostic value of physical signs and symptoms.
        J Card Fail. 2003; 9: S81
        • Kaye D.M.
        • Lambert G.W.
        • Lefkovits J.
        • et al.
        Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure.
        J Am Coll Cardiol. 1994; 23: 570-578
        • Harding S.
        • Sayers S.
        • Dieke A.
        • et al.
        Exacerbations of heart failure as an index of treatment outcome.
        Ann Behav Med. 2003; (abstr.): S141
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • et al.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Schulz R.
        • Beach S.R.
        • Ives D.G.
        • et al.
        Association between depression and mortality in older adults: the Cardiovascular Health Study.
        Arch Intern Med. 2000; 160: 1761-1768
        • Green C.P.
        • Porter C.B.
        • Bresnahan D.R.
        • et al.
        Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure.
        J Am Coll Cardiol. 2000; 35: 1245-1255
        • Guyatt G.H.
        • Sullivan M.J.
        • Thompson P.J.
        • et al.
        The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure.
        CMAJ. 1985; 132: 919-923
        • Cohen J.
        A coefficient of agreement for nominal scales.
        Educ Psychol Meas. 1960; 20: 37-46
        • American Heart Association
        Heart Disease and Stroke Statistics—2005 Update.
        2005 (Vol. 2005. Dallas, TX)
        • McCullough P.A.
        • Philbin E.F.
        • Spertus J.A.
        • et al.
        Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study.
        J Am Coll Cardiol. 2002; 39: 60-69
        • Philbin E.F.
        • DiSalvo T.G.
        Influence of race and gender on care process, resource use, and hospital-based outcomes in congestive heart failure.
        Am J Cardiol. 1998; 82: 76-81
        • Alexander M.
        • Grumbach K.
        • Remy L.
        • et al.
        Congestive heart failure hospitalizations and survival in California: patterns according to race/ethnicity.
        Am Heart J. 1999; 137: 919-927
        • Exner D.V.
        • Dries D.L.
        • Domanski M.J.
        • et al.
        Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction.
        N Engl J Med. 2001; 344: 1351-1357
        • Gillum R.F.
        The epidemiology of cardiovascular disease in black Americans.
        N Engl J Med. 1996; 335: 1597-1599
        • Dries D.L.
        • Exner D.V.
        • Gersh B.J.
        • et al.
        Racial differences in the outcome of left ventricular dysfunction.
        N Engl J Med. 1999; 340: 609-616
        • Wong M.D.
        • Shapiro M.F.
        • Boscardin W.J.
        • et al.
        Contribution of major diseases to disparities in mortality.
        N Engl J Med. 2002; 347: 1585-1592
        • SAS. (SAS Institute Inc.)
        SASSTAT Software, Version 9.1.
        2002 (Cary, NC)
        • Hunt S.A.
        • Baker D.W.
        • Chin M.H.
        • et al.
        ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary.
        J Am Coll Cardiol. 2001; 38: 2101-2113
        • Fleiss J.L.
        Measuring nominal scale agreement among many raters.
        Psych Bull. 1971; 76: 378-382
        • Spertus J.
        • Peterson E.
        • Conard M.W.
        • et al.
        Monitoring clinical changes in patients with heart failure: a comparison of methods.
        Am Heart J. 2005; 150: 707-715
        • Wang C.S.
        • FitzGerald J.M.
        • Schulzer M.
        • et al.
        Does this dyspneic patient in the emergency department have congestive heart failure?.
        JAMA. 2005; 294: 1944-1956