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• Pragmatic use of angiotensin converting enzyme inhibitors in patients with systemic right ventricles
  Piotr Szymañski
  Published on: 23 November 2015

• Published on: 23 November 2015

  Pragmatic use of angiotensin converting enzyme inhibitors in patients with systemic right ventricles

  • Piotr Szymañski, cardiologist
  • Other Contributors:
    • Anna Klisiewicz, Piotr Hoffman

  In the recent paper presenting the latest insights into the therapeutic options for patients with systemic right ventricles, Winter et al., (1) argued that “the pragmatic use of angiotensin converting enzyme inhibitors and beta-blockers in these patients seems appropriate”. However they also concluded that “the evidence- base for the implementation of left ventricular failure treatment regimes in patients with a systemic...

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  In the recent paper presenting the latest insights into the therapeutic options for patients with systemic right ventricles, Winter et al., (1) argued that “the pragmatic use of angiotensin converting enzyme inhibitors and beta-blockers in these patients seems appropriate”. However they also concluded that “the evidence- base for the implementation of left ventricular failure treatment regimes in patients with a systemic right ventricle is poor” and that “most studies were underpowered, had short follow-up periods, or had a retrospective study set-up”.

  There is, however, another important reason for the failure to demonstrate the efficacy of angiotensin converting enzyme inhibitors, angiotensin II and beta-blockers in patients with systemic right ventricles. The use of renin-angiotensin-aldosterone axis inhibitors with systemic right ventricles has been based on extrapolation from the results of classic heart failure trials, but these drugs were used indiscriminately in patients with systemic right ventricles in all published intervention studies; irrespective of the presence or absence of systolic dysfunction, of the patients’ symptoms, or the degree of neurohumoral activation.

  The population of patients with systemic right ventricle is heterogeneous, however. In our series (2), only about half had impaired systolic function, a quarter had symptomatic right ventricular dysfunction and another quarter had asymptomatic right ventricular dysfunction. These finding were similar to those observed by other authors and are concordant with the variable degree of neurohumoral activation in patients with systemic right ventricles. In our patients, approximately two thirds had normal levels of angiotensin II and almost 40% had normal aldosterone levels.(submitted for publication) These observations are comparable to those reported by Dore et al. (3) and are not surprising, because normal renin-angiotensin-aldosterone axis activity is also seen in patients with asymptomatic left ventricular dysfunction and chronic stable heart failure (4).

  The majority of patients with systemic right ventricles are asymptomatic or mildly symptomatic and have minimal baseline activation of the renin-angiotensin-aldosterone system. They are therefore, in a way, similar to patients with left ventricular failure dysfunction participating, for instance, in the SOLVD trial (5). In this trial it was estimated, that the treatment of 1000 such individuals with enalapril for about 3 years would prevent 56 premature deaths over 10 years.(5) If this outcome was applied directly to the approximately 11,000 adult American patients with complete transposition of the great arteries, it would prevent approximately 600 deaths from right ventricular failure.

  The important issue, therefore, is the need for appropriately defined population(s) of patients with systemic right ventricles, in which it is possible to distinguish the efficacy of pharmacotherapy in those who are symptomatic or asymptomatic, or who have preserved or impaired function of the systemic right ventricle. These matters can only be properly addressed by a multi-centre randomised trial.

  Until the results of such a trial are available, it is pragmatic to use angiotensin enzyme converting inhibitors in patients with symptomatic and asymptomatic systemic right ventricular dysfunction (2) as well as in patients with elevated and “high normal” blood pressure readings, irrespective of right ventricular function (6).

  References:

  1. Winter MM, Bouma BJ, Groenink M, et al. Latest insights in therapeutic options for systemic right ventricular failure: a comparison with left ventricular failure. Heart 2009;95: 960-963.

  2. Szymañski P, Klisiewicz A, Lubiszewska B, et al. Application of Classic Heart Failure Definitions of Asymptomatic and Symptomatic Ventricular Dysfunction and Heart Failure Symptoms With Preserved Ejection Fraction to Patients With Systemic Right Ventricles. Am J Card. 2009, DOI: 10.1016/j.amjcard.2009.03.057

  3. Dore A, Houde C, Chan KL, et al. Angiotensin receptor blockade and exercise capacity in adults with systemic right ventricles: a multicenter, randomized, placebo-controlled clinical trial. Circulation. 2005;112:2411- 16.

  4. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990;82:1724-9.

  5. Jong P, Yusuf S, Rousseau MF, et al. Effect of enalapril on 12- year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. Lancet, 2003;361:1843-1848.

  6. Szymañski P, Hoffman P, Lubiszewska B et al. The relationship between blood pressure, pulse pressure and right ventricular function following an atrial switch procedure for complete transposition of the great arteries. Int J Cardiol. 2005;101:59-63.

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  Conflict of Interest:
  None declared.

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