Correspondence
Prognosis in Heart Failure with a Normal Ejection Fraction
N Engl J Med 2007; 357:829-830August 23, 2007
- Article
To the Editor:
Recent studies have shown a poor prognosis for patients with heart failure who have a normal ejection fraction,1 a finding that differs markedly from the results of randomized, controlled trials.2,3 This discrepancy requires an explanation.
Many patients with heart failure who have serious, common coexisting illnesses, such as pulmonary disease, atrial fibrillation, and renal dysfunction (all of which are both markers and mediators of a worse outcome), are excluded from randomized, controlled trials for two obvious reasons. First, heart failure with a normal ejection fraction is largely a diagnosis of exclusion, and patients with coexisting illnesses are excluded in order to ensure that symptoms and signs are cardiac in origin. Second, if the outcome is determined by coexisting illnesses, then an intervention directed at heart failure may be ineffective. In addition, low event rates may reflect the inclusion of patients without important cardiac disease.4 Clearly, a test that identifies which patients with heart failure who have a normal ejection fraction are at increased risk for cardiovascular events would be desirable. So far, the success of echocardiography in this regard has been limited.
The Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) trial compared the effects of perindopril and placebo in 850 patients 70 years of age or older who had heart failure and echocardiographic markers suggesting diastolic heart failure.3 Perindopril, an angiotensin-converting–enzyme (ACE) inhibitor, improved symptoms and walking distance and reduced hospitalization for heart failure during the first 12 months after randomization. Effects on hospitalization waned thereafter, possibly because many patients who had been assigned to the control group subsequently took ACE inhibitors. We measured plasma concentrations of N-terminal pro–brain natriuretic peptide (NT-proBNP) at baseline in 375 patients, 207 (55%) of whom were women. The median age was 77 years (interquartile range, 72 to 80), the median left ventricular ejection fraction was 64% (interquartile range, 56 to 66), and the median NT-proBNP level was 409 pg per milliliter (interquartile range, 176 to 1036; full range, 8 to 13,328). For comparison, in a large survey, only 5% of healthy women and men over the age of 70 years had values of NT-proBNP that were more than 123 pg per milliliter and more than 67 pg per milliliter, respectively.5 The hazard ratios for death or hospitalization for heart failure were 1.38 (95% confidence interval [CI], 0.64 to 2.99) in the second quartile of NT-proBNP values, 2.84 (95% CI, 1.42 to 5.72) in the third quartile, and 4.47 (95% CI, 2.30 to 8.72) in the fourth quartile, as compared with the lowest quartile (Figure 1Figure 1
Rates of Death or Hospitalization for Heart Failure at 1 and 2 Years after Randomization among Patients in the PEP-CHF Trial, According to the Quartile of N-Terminal Pro–Brain Natriuretic Peptide (NT-proBNP) Levels.). The subgroup with NT-proBNP measurements was not large enough to determine whether there was any interaction with the effects of perindopril. Future clinical trials assessing mortality and morbidity in such patients should consider the use of NT-proBNP levels to guide the selection of patients, which would allow for the recruitment of patients with coexisting noncardiac illnesses but with a high risk of cardiovascular events and for the exclusion of low-risk patients who have little to gain from treatment.John G.F. Cleland, M.D.
University of Hull, Kingston-upon-Hull HU6 7RX, United Kingdom
j.g. cleland@hull. ac. uk Jacqueline Taylor, M.B., Ch.B.
Glasgow Royal Infirmary, Glasgow G32 6ND, ScotlandMichal Tendera, M.D., Ph.D.
Silesian School of Medicine, 40-635 Katowice, PolandDrs. Cleland, Taylor, and Tendera report receiving honoraria and grant support from Servier. No other potential conflict of interest relevant to this letter was reported.
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- Citing Articles (19)
Citing Articles
1
C. M. Carlsen, M. Bay, V. Kirk, J. P. Gotze, L. Kober, O. W. Nielsen. (2012) Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide: a 10-year analysis from the Copenhagen Hospital Heart Failure Study. European Journal of Heart Failure
CrossRef2
Thibaud Damy, Anna Kallvikbacka-Bennett, Kevin Goode, Olga Khaleva, Christian Lewinter, James Hobkirk, Nikolay P. Nikitin, Jean-Luc Dubois-Randé, Luc Hittinger, Andrew L. Clark, John G.F. Cleland. (2012) Prevalence of, Associations With, and Prognostic Value of Tricuspid Annular Plane Systolic Excursion (TAPSE) Among Outatients Referred for the Evaluation of Heart Failure. Journal of Cardiac Failure
CrossRef3
T. Damy, A. Kallvikbacka-Bennett, J. Zhang, K. Goode, L. Buga, J. Hobkirk, A. Yassin, J.-L. Dubois-Rande, L. Hittinger, J. G. F. Cleland, A. L. Clark. (2011) Does the physical examination still have a role in patients with suspected heart failure?. European Journal of Heart Failure 13:12, 1340-1348
CrossRef4
G. Michael Felker. (2011) Biomarkers as Surrogate End Points in Heart Failure Trials. Heart Failure Clinics 7:4, 501-507
CrossRef5
D. Burkhoff. (2011) Mortality in heart failure with preserved ejection fraction: an unacceptably high rate. European Heart Journal
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Aaron M. From, Barry A. Borlaug. (2011) Heart Failure with Preserved Ejection Fraction: Pathophysiology and Emerging Therapies. Cardiovascular Therapeutics 29:4, e6-e21
CrossRef7
Husam M. Abdel-Qadir, Shaan Chugh, Douglas S. Lee. (2011) Improving Prognosis Estimation in Patients with Heart Failure and the Cardiorenal Syndrome. International Journal of Nephrology 2011, 1-11
CrossRef8
Margaret M. Redfield. 2010. Recognising and Managing the Patient with Heart Failure and Preserved Ejection Fraction. , 255-286.
CrossRef9
Sally C Inglis, Robyn A Clark, Finlay A McAlister, Jocasta Ball, Christian Lewinter, Damien Cullington, Simon Stewart, John GF Cleland, Sally C Inglis. 2010. Structured telephone support or telemonitoring programmes for patients with chronic heart failure. .
CrossRef10
Robert S. Mckelvie, Michel Komajda, John Mcmurray, Michael Zile, Agata Ptaszynska, Mark Donovan, Peter Carson, Barry M. Massie. (2010) Baseline Plasma NT-proBNP and Clinical Characteristics: Results From the Irbesartan in Heart Failure With Preserved Ejection Fraction Trial. Journal of Cardiac Failure 16:2, 128-134
CrossRef11
Otto Kamp, Marco Metra, Gilles W. Keulenaer, Burkert Pieske, Viviane Conraads, José Zamorano, Lieven Huysse, Panos E. Vardas, Michael Böhm, Livio Dei Cas. (2010) Effect of the long-term administration of nebivolol on clinical symptoms, exercise capacity and left ventricular function in patients with heart failure and preserved left ventricular ejection fraction: background, aims and design of the ELANDD study. Clinical Research in Cardiology 99:2, 75-82
CrossRef12
John G.F. Cleland, John J.V. McMurray, John Kjekshus, Jan H. Cornel, Peter Dunselman, Cândida Fonseca, Åke Hjalmarson, Jerzy Korewicki, Magnus Lindberg, Naresh Ranjith, Dirk J. van Veldhuisen, Finn Waagstein, Hans Wedel, John Wikstrand. (2009) Plasma Concentration of Amino-Terminal Pro-Brain Natriuretic Peptide in Chronic Heart Failure: Prediction of Cardiovascular Events and Interaction With the Effects of Rosuvastatin. Journal of the American College of Cardiology 54:20, 1850-1859
CrossRef13
J. Farkas, S. Nabb, L. Zaletel-Kragelj, J. G.F. Cleland, M. Lainscak. (2009) Self-rated health and mortality in patients with chronic heart failure. European Journal of Heart Failure 11:5, 518-524
CrossRef14
W.H. Wilson Tang, Gary S. Francis. (2008) The Year in Heart Failure. Journal of the American College of Cardiology 52:20, 1671-1678
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John GF Cleland, Damien Cullington, Olga Khaleva, Ahmed Tageldien. (2008) Cardiac resynchronization therapy: dyssynchrony imaging from a heart failure perspective. Current Opinion in Cardiology 23:6, 634-645
CrossRef16
M. Metra, L. Dei Cas, B. M. Massie. (2008) Treatment of heart failure in the elderly: never say it's too late. European Heart Journal 30:4, 391-393
CrossRef17
Jasmine Grewal, Robert S. McKelvie, Hans Persson, Peter Tait, Jonas Carlsson, Karl Swedberg, Jan Ostergren, Eva Lonn. (2008) Usefulness of N-Terminal Pro–Brain Natriuretic Peptide and Brain Natriuretic Peptide to Predict Cardiovascular Outcomes in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction. The American Journal of Cardiology 102:6, 733-737
CrossRef18
Maral Ouzounian, Douglas S Lee, Peter P Liu. (2008) Diastolic heart failure: mechanisms and controversies. Nature Clinical Practice Cardiovascular Medicine 5:7, 375-386
CrossRef19
John GF Cleland, Stephen L Atkin. (2007) Thiazolidinediones, deadly sins, surrogates, and elephants. The Lancet 370:9593, 1103-1104
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