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• Author's response
  John E Sanderson
  Published on: 23 November 2015
• Interesting findings in The Hong Kong Heart Failure Study
  Eduardo Rosa
  Published on: 23 November 2015

• Published on: 23 November 2015

  Author's response

  • John E Sanderson
  • Other Contributors:
    • Gabriel W Yip and Mei Wang

  Dear Editor,

  We appreciate the interest of Rosa et al in our study.[1] They raise 3 points with respect to our results.[2] The first queries whether we had left out the subjects dropped out during the course of the study, which might have overestimated the clinical effectiveness of the treatment arms. The second deals with the additional beneficial effects of irbesartan and ramipril beyond their blood pressure c...

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  Dear Editor,

  We appreciate the interest of Rosa et al in our study.[1] They raise 3 points with respect to our results.[2] The first queries whether we had left out the subjects dropped out during the course of the study, which might have overestimated the clinical effectiveness of the treatment arms. The second deals with the additional beneficial effects of irbesartan and ramipril beyond their blood pressure control. The third concerns the calculation of LV mass based on dimensions of the left ventricle at end- diastole.

  All our patients were analyzed on the basis of intention-to-treat, including all the cases up to their pre-defined follow-up at week 12, 24 or 52 before their withdrawal for various reasons as stated in the results section. The unequal randomization of patients into the three treatment arms that might have given Rosa et al a false impression of excluding drop -out cases for the analysis was due to our original intention of enrolling 400 patients with designated sequence of random allocation. The recruitment process was slow for reasons as mentioned in the limitations section. As the result, the sample of patients recruited for the three arms were unfortunately relatively small and, therefore, we were unable to detect any significant changes in terms of LV mass by 2-dimensional echocardiography. This issue warrants further study with a larger cohort of patients.[3]

  It is tantalizing to speculate that irbesartan with or without ramipril have additional beneficial effects on the myocardium and peripheral vascular endothelium beyond blood pressure control in patients suffering from heart failure with normal ejection fraction (HFNEF). For example, the relationship between arterial compliance and diastolic dysfunction is clearly important. [4]. However this interesting notion will require proof in HFNEF patients and deserves a further large-scale prospective randomized study, given the magnitude of this vexing clinical problem in Hong Kong and worldwide.[5,6]. Interestingly we found that cough was much less of a problem than predicted in an Asian population and our cough rate in the ramipril group (10%) is comparable to previous studies in the West.

  The comments on the effect of diuretics on left ventricular dimension are well taken and relevant but the formula we used is well established and widely used. Furthermore, all three patient groups received diuretics so the effect would have been similar. Future studies could use 3D- echocardiography or MRI for more accurate assessment of LV mass.

  References

  1. Rosa EM, Träsel HAV, Gravina LB.
  Interesting findings in The Hong Kong Heart Failure Study.
  Heart 2008 eLetters Online 24 May 2008

  2. Yip GW, 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.

  3. Carson P, Massie BM, McKelvie R, et al.
  The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design.
  J Cardiac Fail 2005;11:576–585.

  4. P M Mottram, B A Haluska, R Leano, S Carlier, C Case, and T H Marwick
  Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease
  Heart 2005; 91: 1551 - 1556.

  5. Yip GWK, Ho PPY, Woo KS, Sanderson JE
  Comparison of frequencies of left ventricular systolic and diastolic heart failure in Chinese living in Hong Kong.
  Am J Cardiol 1999;84:563-567.

  6. Sanderson JE.
  Heart failure with a normal ejection fraction.
  Heart. 2007;93:155-8.

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  Conflict of Interest:
  None declared.

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• Published on: 23 November 2015

  Interesting findings in The Hong Kong Heart Failure Study

  • Eduardo Rosa
  • 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 the medical literature are related to studies that observe subjects with heart failure followed by systolic dysfunction. It is notable that Yip et al. (2) in their article assess the quality of l...

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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 the medical literature are related to studies that observe subjects with heart failure followed by systolic dysfunction. It is notable that Yip et al. (2) in their 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. 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), neither do they present adverse events, like irritative coughs.

  3. Ventricular mass is inferred from a mathematical calculation, which depends on intraventricular diameter(5). The usage of diuretics decreases preload, consequently, there is a decrease in left ventricle internal diameter. Mathematically speaking, a reduction in ventricular mass occurs. This effect may 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) 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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