CLINICAL STUDY: HEART FAILURE
Circadian variation in the effects of aldosterone blockade on heart rate variability and QT dispersion in congestive heart failure
Kok-Meng Yee, MRCP*,
Stuart D. Pringle, MD, FRCP and
Allan D. Struthers, MD, FRCP, FESC*
* University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, United Kingdom
Department of Cardiology, Ninewells Hospital and Medical School, Dundee, United Kingdom
Manuscript received June 2, 2000;
revised manuscript received January 31, 2001,
accepted February 13, 2001.
Reprint requests and correspondence: Dr. K. M. Yee, Cardiac Unit, Papworth Hospital, Papworth Everard, Cambridge, United Kingdom
kokmengyee{at}hotmail.com
OBJECTIVES
The study was designed to comprehensively evaluate the circadian effects of aldosterone blockade on autonomic tone and QT dispersion in chronic heart failure (CHF).
BACKGROUND
Spironolactone therapy given in addition to angiotensin-converting enzyme inhibitors improved survival in CHF, but the mechanism of its benefit is uncertain. Experimental evidence suggests that aldosterone may have detrimental effects on the autonomic nervous system, especially during the morning hours.
METHODS
Twenty-eight patients with New York Heart Association class II to IV CHF received spironolactone 50 mg daily and placebo for four weeks each in a double-blind crossover fashion. After each treatment phase, a full circadian assessment was undertaken of spironolactone’s autonomic effects. The assessment included monitoring heart rate, QT dispersion, continuous Holter recordings, heart rate variability (HRV) and norepinephrine kinetics.
RESULTS
Spironolactone significantly reduced all indices of QT dispersion. The reductions in QTcmax, QTd and QTcd were greatest at 6 AM. In addition, spironolactone had favorable autonomic effects, which were limited to the morning (6–10 AM), including heart rate reduction and an improvement in HRV.
CONCLUSIONS
Spironolactone reduced heart rate and improved HRV and QT dispersion in CHF. Its effects were particularly prominent during the morning hours.
|
Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | CHF | = chronic heart failure | | CQTc | = corrected QT dispersion | | ECG | = electrocardiogram | | HF | = high frequency | | HPLC | = high-performance liquid chromatography | | HRV | = heart rate variability | | LF | = low frequency | | MIBG | = metaiodobenzylguanidine | | NA | = norepinephrine | | NYHA | = New York Heart Association | | QTd | = QT interval dispersion | | RALES | = Randomized Aldactone Evaluation Study | | SCD | = sudden cardiac death |
|
This article has been cited by other articles:
|
|
|
|
 
A. Karagiannis, K. Tziomalos, A. I Kakafika, V. G Athyros, F. Harsoulis, and D. P Mikhailidis
Medical treatment as an alternative to adrenalectomy in patients with aldosterone-producing adenomas
Endocr. Relat. Cancer,
September 1, 2008;
15(3):
693 - 700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Muto, N. Ueda, T. Opthof, T. Ohkusa, K. Nagata, S. Suzuki, Y. Tsuji, M. Horiba, J.-K. Lee, H. Honjo, et al.
Aldosterone modulates If current through gene expression in cultured neonatal rat ventricular myocytes
Am J Physiol Heart Circ Physiol,
November 1, 2007;
293(5):
H2710 - H2718.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Berry, N. Murphy, G. De Vito, S. Galloway, A. Seed, C. Fisher, N. Sattar, P. Vallance, W. S. Hillis, and J. McMurray
Effects of aldosterone receptor blockade in patients with mild-moderate heart failure taking a beta-blocker
Eur J Heart Fail,
April 1, 2007;
9(4):
429 - 434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Groban and J. Butterworth
Perioperative management of chronic heart failure.
Anesth. Analg.,
September 1, 2006;
103(3):
557 - 575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Pitt and B. Pitt
Aldosterone, ion channels, and sudden death: another piece of the circle?
Am J Physiol Heart Circ Physiol,
June 1, 2006;
290(6):
H2176 - H2177.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Chai, I. M. Garrelds, R. de Vries, and A.H. Jan Danser
Cardioprotective Effects of Eplerenone in the Rat Heart: Interaction With Locally Synthesized or Blood-Derived Aldosterone?
Hypertension,
April 1, 2006;
47(4):
665 - 670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. C Shah, S. Pringle, and A. Struthers
Aldosterone Blockade Over and Above ACE-Inhibitors in Patients with Coronary Artery Disease but without Heart Failure
Journal of Renin-Angiotensin-Aldosterone System,
March 1, 2006;
7(1):
20 - 30.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. H. W. Tang, A. C. Parameswaran, A. P. Maroo, and G. S. Francis
Aldosterone Receptor Antagonists in the Medical Management of Chronic Heart Failure
Mayo Clin. Proc.,
December 1, 2005;
80(12):
1623 - 1630.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. E. Maser and M. J. Lenhard
Cardiovascular Autonomic Neuropathy Due to Diabetes Mellitus: Clinical Manifestations, Consequences, and Treatment
J. Clin. Endocrinol. Metab.,
October 1, 2005;
90(10):
5896 - 5903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ouvrard-Pascaud, Y. Sainte-Marie, J.-P. Benitah, R. Perrier, C. Soukaseum, A. N. D. Cat, A. Royer, K. Le Quang, F. Charpentier, S. Demolombe, et al.
Conditional Mineralocorticoid Receptor Expression in the Heart Leads to Life-Threatening Arrhythmias
Circulation,
June 14, 2005;
111(23):
3025 - 3033.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Milliez, X. Girerd, P.-F. Plouin, J. Blacher, M. E. Safar, and J.-J. Mourad
Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism
J. Am. Coll. Cardiol.,
April 19, 2005;
45(8):
1243 - 1248.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Agostoni, A. Magini, D. Andreini, M. Contini, A. Apostolo, M. Bussotti, G. Cattadori, and P. Palermo
Spironolactone improves lung diffusion in chronic heart failure
Eur. Heart J.,
January 2, 2005;
26(2):
159 - 164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Pitt
Generic drugs in cardiology: will they reduce health care costs?
J. Am. Coll. Cardiol.,
July 7, 2004;
44(1):
10 - 13.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J E Macdonald, N Kennedy, and A D Struthers
Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment
Heart,
July 1, 2004;
90(7):
765 - 770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Fletcher, A. N. Buch, H. C. Routledge, S. Chowdhary, J. H. Coote, and J. N. Townend
Acute aldosterone antagonism improves cardiac vagal control in humans
J. Am. Coll. Cardiol.,
April 7, 2004;
43(7):
1270 - 1275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D Struthers
Aldosterone blockade in heart failure
Journal of Renin-Angiotensin-Aldosterone System,
March 1, 2004;
5(1_suppl):
S23 - S27.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. Pitt, C. T Stier Jr, and S. Rajagopalan
Mineralocorticoid receptor blockade: new insights into the mechanism of action in patients with cardiovascular disease
Journal of Renin-Angiotensin-Aldosterone System,
September 1, 2003;
4(3):
164 - 168.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. Pitt
Aldosterone Blockade in Patients With Acute Myocardial Infarction
Circulation,
May 27, 2003;
107(20):
2525 - 2527.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Pitt, W. Remme, F. Zannad, J. Neaton, F. Martinez, B. Roniker, R. Bittman, S. Hurley, J. Kleiman, M. Gatlin, et al.
Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction
N. Engl. J. Med.,
April 3, 2003;
348(14):
1309 - 1321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Caballero, I. Moreno, T. Gonzalez, C. Arias, C. Valenzuela, E. Delpon, and J. Tamargo
Spironolactone and Its Main Metabolite, Canrenoic Acid, Block Human Ether-a-Go-Go-Related Gene Channels
Circulation,
February 18, 2003;
107(6):
889 - 895.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C A J Farquharson and A D Struthers
Increasing plasma potassium with amiloride shortens the QT interval and reduces ventricular extrasystoles but does not change endothelial function or heart rate variability in chronic heart failure
Heart,
December 1, 2002;
88(5):
475 - 480.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Rousseau, O. Gurne, D. Duprez, W. Van Mieghem, A. Robert, S. Ahn, L. Galanti, J.-M. Ketelslegers, and Belgian RALES Investigators
Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: Results from the RALES neurohormonal substudy
J. Am. Coll. Cardiol.,
November 6, 2002;
40(9):
1596 - 1601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D Struthers
Review: Aldosterone-induced vasculopathy: a new reversible cause of cardiac death
Journal of Renin-Angiotensin-Aldosterone System,
December 1, 2001;
2(4):
211 - 214.
[PDF]
|
|
|
|
