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• Exercise Capacity in Diastolic Heart Failure
  Jackie Taylor
  Published on: 2 August 2008
• Interesting findings in The Hong Kong Heart Failure Study
  Eduardo M Rosa
  Published on: 24 May 2008

• Published on: 2 August 2008

  Exercise Capacity in Diastolic Heart Failure

  • Jackie Taylor, Consultant Physician
  • Other Contributors:
    • Michael Tendera, John GF Cleland

  Dear Editor,

  We read with great interest the article by Yip and colleagues, reporting the results of a randomised controlled trial of diuretics, irbesartan and ramipril in patients with heart failure and normal ejection fraction(1). The authors are to be commended for their contribution to the evidence base for the management of this condition. The PROBE design tested the hypothesis that addition of ramipril or...

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  Dear Editor,

  We read with great interest the article by Yip and colleagues, reporting the results of a randomised controlled trial of diuretics, irbesartan and ramipril in patients with heart failure and normal ejection fraction(1). The authors are to be commended for their contribution to the evidence base for the management of this condition. The PROBE design tested the hypothesis that addition of ramipril or irbesartan would be superior to diuretics alone and evaluated quality of life, exercise capacity, ventricular function and NT-pro-BNP levels in three groups of 50 patients. Quality of Life Score ( Minnesota Heart Failure Symptom Questionnaire) improved significantly and similarly in all three groups between baseline and 52 weeks. Exercise capacity assessed by 6 minute walk test at baseline and 24 weeks improved only slightly. The authors suggest that this may be because the test is not robust enough to identify effective treatment or that older patients have too many competing factors which influence mobility. Our experience differs from this. 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,( mean age 76) who had heart failure and echocardiographic markers suggesting diastolic heart failure(2). Perindopril reduced heart failure hospitalisations and improved symptoms at one year. There was also a statistically significant increase in 6 minute walk distance in patients assigned to perindopril over 1 year of follow up, with a mean difference in change of 14m (3 to 25, p<0.011)(3). A change of this magnitude is both statistically significant and clinically relevant.

  The baseline characteristics of patients in both studies were very similar, although patients in PEP-CHF were slightly older, had a higher prevalence of prior myocardial infarction and their baseline exercise capacity was poorer. Despite this, important benefits in function were seen in PEP-CHF with active treatment. The Hong Kong Study evaluated 6 minute walk distance after 24 weeks of treatment and it is possible that this was too short a time for effects on exercise capacity to be demonstrable.

  The 6 minute walk distance has previously been evaluated in frail, older patients with heart failure (4). O’Keefe’s study included frail patients with multiple comorbidity, median age 81 years (range 74-92 years) and showed that the 6 minute walk test was both reproducible and responsive.

  We agree entirely with the authors that, particularly for older patients, improvements in symptoms and exercise capacity are as important as mortality benefits, and would encourage clinicians to use the 6 minute walk test as a simple and meaningful outcome measure in heart failure.

  REFERENCES

  1. Yip GWK, Wang M, Wang T et al.
  The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction.
  Heart 2008;94:573-80.

  2.Cleland JGF, Tendera M, Adamus J et al
  Perindopril for elderly people with heart failure: the PEP-CHF Study.
  Eur J Heart Fail 2001;1:211-17

  3.Cleland JGF, Tendera M, Adamus J et al
  The perindopril in elderly people with chronic heart failure (PEP-CHF) study
  Eur Heart J 2006;27:2338-45

  4. O’Keeffe ST, Lye M, Donellan C et al.
  Reproducibility and responsiveness of quality of life assessment and six minute walk test in elderly heart failure patients.
  Heart 1998;80:377-382.

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  Conflict of Interest:
  None declared.

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• Published on: 24 May 2008

  Interesting findings in The Hong Kong Heart Failure Study

  • Eduardo M Rosa, Coordinator of Institute of Clinical Research for Multicenter Studies
  • Other Contributors:
    • Henrique A V Träsel and Lívia B Gravina

  Dear Editor,

  Patients with heart failure and a normal left ventricular systolic function correspond to almost half of all patients with congestive heart failure(1). However, the great majority of the data presented in medical literature are related to studies that observe subjects with heart failure followed by systolic disfunction. It is notable that Yip et al. (2) in your article assess the quality of life and...

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  Dear Editor,

  Patients with heart failure and a normal left ventricular systolic function correspond to almost half of all patients with congestive heart failure(1). However, the great majority of the data presented in medical literature are related to studies that observe subjects with heart failure followed by systolic disfunction. It is notable that Yip et al. (2) in your article assess the quality of life and global and regional ventricular function in heart failure with normal ejection fraction.

  After reading with interest The Hong Kong Heart Failure Study(2), we considered this study revealed important findings and, among those, three have caught our attention:

  1. The subjects who left the study due to adverse effects were not included in final analysis and, consequently, did not provide changes in final results. In according to Fischer et al.(3), clinical effectiveness may be overestimated if an intention to treat analysis is not done.

  2. Both drugs Irbesartan and Ramipril do not play their roles like anti-hypertensive agents, as should be expected(4-9), neither they present adverse events, like irritative coughs.

  3. Ventricular mass is inferred from a mathematical calculation, which depends on intraventricular diameter(10). The usage of diuretics decreases preload, consequently, there is a decrease in left ventricle intern diameter. Mathematically speaking, a reduction on ventricular mass occurs. This effect maybe would not be reproduced if a direct anatomic analysis was conducted.

  References

  (1) Sanderson JE.
  Heart failure with a normal ejection fraction.
  Heart. 2007 Feb;93(2):155-8.

  (2) Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, et al.
  The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction.
  Heart. 2008 May;94(5):573-80.

  (3) Fisher L, Dixon D, Herson J, Frankowski R, Hearon M, Pearce K.
  Intention to treat in clinical trials. In: Pearce K, editor. Statistical issues in drug research and development.
  New York: Marcel Dekker; 1990: 331-50.

  (4) Franklin S, Lapuerta P, Cox D, Donovan M.
  Initial combination therapy with irbesartan/hydrochlorothiazide for hypertension: an analysis of the relationship between baseline blood pressure and the need for combination therapy.
  J Clin Hypertens (Greenwich). 2007 Dec;9(12 Suppl 5):15-22.

  (5) Raskin P, Guthrie R, Flack J, Reeves R, Saini R.
  The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide.
  J Hum Hypertens. 1999 Oct;13(10):683-7.

  (6) Lapuerta P.
  Irbesartan/HCTZ as initial treatment in patients with moderate hypertension.
  16th Meeting of the European Society of Hypertension; 2006; Madrid, Spain; 2006.

  (7) Neutel JM, Franklin SS, Lapuerta P, Bhaumik A, Ptaszynska A.
  A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension.
  J Hum Hypertens. 2008 Apr;22(4):266-74.

  (8) Heidbreder D, Froer KL, Breitstadt A, Cairns V, Langley A, Bender N.
  Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to ramipril monotherapy.
  Clin Cardiol. 1992 Dec;15(12):904-10.

  (9) Genthon R.
  Study of the efficacy and safety of the combination ramipril 2.5 mg plus hydrochlorothiazide 12.5 mg in patients with mild-to-moderate hypertension. ATHES Study Group.
  Int J Clin Pharmacol Res. 1994;14(1):1-9.

  (10) Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al.
  Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.
  J Am Soc Echocardiogr. 2005 Dec;18(12):1440-63.

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  Conflict of Interest:
  None declared.

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