Author + information
- Michael F. O'Rourke, DSc, MD* ()
- ↵*St. Vincent's Clinic, 438 Victoria Street, Suite 810, Darlinghurst, Sydney NSW 2010, Australia
The paradox in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) study (1) needs to be explained if low brachial systolic pressure is perceived by physicians as a contraindication to the use of arterial dilator drugs such as nitrates, carvedilol, and candesartan in systolic heart failure. Meredith et al. (1) extended results of previous studies (AHeFT [African-American Heart Failure Trial (2)] and COPERNICUS [Carvedilol Prospective Randomized Cumulative Survival (3)]) in showing that an arterial vasodilator was at least as effective in trials of cardiac failure for improving outcomes in patients with systolic blood pressure (SBP) <100 mm Hg (whose left ventricular ejection fraction averaged 25%) as in those with normal or high SBP and without appreciable risk of causing symptomatic hypotension.
The paradox arises from exclusive consideration of brachial rather than central pressure (4) and from assuming that effects of dilator drugs on high-resistance arterioles dominate over effects on low-resistance conduit arteries. Arterial vasodilator drugs such as nitroglycerin reduce wave reflection (5,6) and “trap” reflected pressure waves in the peripheral circulation so that they do not summate with central systolic pressure, with this differentially reduced compared with brachial SBP (4,6). In patients with a low left ventricular ejection fraction and the ventricle contracting weakly and acting (in engineering terms) as a “pressure source” (6,7), reduction in aortic and left ventricular systolic pressure leads to increased left ventricular ejection from the heart (6,7). Such an increase in stroke volume can maintain or increase SBP in patients with cardiac failure due to systolic dysfunction.
The paradox described by Meredith et al. (1) is explicable. It explains why drugs that dilate muscular arteries and reduce wave reflection are very effective for reducing systolic pressure in hypertension when the heart is contracting normally (i.e., as a flow source) (6,7) and for increasing cardiac output in patients with heart failure when the heart's contraction is weakened, and it acts as a pressure source (6,7).
Consideration of blood pressure, cardiac output, and peripheral resistance is insufficient to explain the function of the pulsating heart and blood vessels. These comments are offered without any criticism of the excellent work of Meredith et al. (1).
Due to communication problems, several Letters to the Editor were misplaced and were not published in a timely fashion. We became aware of this recently when one of the authors contacted us as to the publication status. We have gathered those letters together and are now publishing them in this issue. In general, we believe that the letters and the replies are self explanatory. We apologize for this delay.
Please note: Dr. O'Rourke is the founding director of AtCor Medical, Sydney, Australia, maker of a pulse-wave analysis system.
- American College of Cardiology Foundation
- Meredith P.A.,
- Ostergren J.,
- Anand I.,
- et al.
- Anand I.S.,
- Tam S.W.,
- Rector T.S.,
- et al.
- Rouleau J.L.,
- Roecker E.B.,
- Tendera M.,
- et al.
- O'Rourke M.F.,
- Safar M.E.,
- Dzau V.
- Nichols W.W.,
- O'Rourke M.F.