Download Blood pressure and the therapy of advanced heart failure

Journal of the American College of Cardiology
© 2004 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
Blood Pressure
and the Therapy of
Advanced Heart Failure*
Jay N. Cohn, MD
Minneapolis, Minnesota
In the 1960s, when we initially introduced the concept of
vasodilator therapy for the failing heart (1), we had to
overcome skepticism about the safety and efficacy of this
approach. Health care workers were focused on ausculatory
blood pressure (BP), which often was falsely reduced in sick
patients (2), and vasoconstrictor drugs frequently were
administered to restore perceived low pressure, which was
thought to be harmful. The idea that vasodilator drugs,
which are designed to lower pressure, would be safe in such
an individual was anathema.
See page 1423
Our early experience convinced us of the wisdom of this
approach even when the directly measured arterial pressure
was low. One of our first patients was in severe pump failure
after an acute myocardial infarction. Our bedside hemodynamic assessment (3) revealed a brachial arterial pressure of
90/70 mm Hg and a cardiac output of 2.3 l/min. Having
already demonstrated the favorable effects of sodium nitroprusside on cardiac output in such patients (4), we initiated
an infusion which, as expected, doubled cardiac output and
produced dramatic clinical improvement while reducing
arterial pressure to 84/60 mm Hg. Because we were satisfied
with our titration and it was now 2 AM, I left orders with the
nursing staff to maintain systolic pressure ⬍90 mm Hg by
adjusting the dose of nitroprusside. When I returned at
7 AM, the nurse informed me apologetically that she had
failed in her effort. Despite initiating a second intravenous
site for nitroprusside and even pumping the infusion to
maintain a high flow rate, she was unable to keep the
systolic pressure below 90 mm Hg. The patient’s cardiac
output had increased to 7 l/min. The lesson was clear:
Vasodilator drugs given to a patient with severe heart failure
(HF) in whom impedance is limiting cardiac output may
result in a sustained rise in pressure. Pressure is not the
target; flow should be the target!
Despite the clarity of this physiologic principle, clinicians
still often focus on BP in their management of sick patients,
perhaps because it is easy to measure and generates a
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
Vol. 43, No. 8, 2004
ISSN 0735-1097/04/$30.00
doi:10.1016/j.jacc.2004.01.019
number that people think they understand. And because of
that number, patients may be deprived of effective therapy,
such as angiotensin-converting enzyme inhibitors and betablockers. Indeed, nurses often withhold these drugs, even
when they are prescribed, if the BP is low in a hospitalized
patient. Hypotension can of course be a concern when it is
associated with cerebral, cardiac, or renal evidence of inadequate perfusion. But in the absence of such signs or
symptoms, the therapeutic goal is to maintain treatment
with drugs that lower impedance, improve flow, and slow
left ventricular (LV) structural remodeling.
Systolic BP is a product of the stroke volume and the
impedance to ejection. When the heart is healthy, impedance does not affect stroke volume but rather determines
pressure. In the failing heart, however, impedance controls
stroke volume (5). The neurohormonal and vascular consequences of HF (6) raise impedance, and stroke volume then
becomes a measure of the severity of LV dysfunction. Under
these circumstances, hypotension is a consequence of reduced contractile function of the heart. The hypotensive
patient with HF, therefore, should be at high risk because of
the severity of HF and should be a candidate for the most
aggressive therapy to lower impedance and slow the progression of structural and functional disease.
The study by Rouleau et al. (7) in this issue of the Journal
is a welcome reminder of the fallacy of the concern with low
BP in administering carvedilol. As the authors point out,
low BP is often cited as a reason for not administering a
beta-blocker in HF despite the impressive data supporting
its long-term efficacy. The vasodilator action of carvedilol
related to its alpha-blocking effects should in fact be
beneficial in such patients, just as it was in our early patient
experience. As nicely documented by Rouleau et al. (7), low
entrance BP in the Carvedilol Prospective Randomized
Cumulative Survival (COPERNICUS) trial was a powerful
mortality risk factor and identified patients in particular
need for aggressive therapy.
It is important to reiterate an often-disregarded principle
in the management of HF. Symptoms of decompensated
HF are a consequence of long-term structural remodeling of
the heart complicated by short-term and often reversible
dysfunction related to heightened impedance and a contractile disorder. Lowering the impedance or increasing the
contractility can reverse the functional disorder (8) but not
necessarily the long-term structural disorder. Beta-blockers
deal with the structural disorder (9). Vasodilators correct the
functional disorder, and some vasodilators (e.g., nitrates,
angiotensin-converting enzyme inhibitors, angiotensin receptor blockers) also favorably affect the structural disorder
(10 –12). Alpha blockers are not among these (10), so the
alpha-blocker activity of carvedilol may be important in
restoring LV function in these hypotensive patients with
HF, but it probably does not contribute to the long-term
structural benefit of the beta-blocking activity of carvedilol.
The message of the Rouleau et al. study (7) should be
JACC Vol. 43, No. 8, 2004
April 21, 2004:1430–1
clear. Hypotension in severe HF is grave and helps physicians identify patients who are in need of aggressive therapy
to improve emptying of the LV and, long-term, to correct
its structural remodeling. Vasodilator therapy can usually be
tolerated by such patients and indeed perhaps should be
mandated. Low BP should not preclude a trial with such
drugs, and a fall in BP not accompanied by hypotensive
signs or symptoms should not necessarily lead to a discontinuation of the therapy.
Carvedilol is dual therapy: Its vasodilator effect supports
LV function, whereas its beta-blocking effect exerts longterm benefits. One could alternatively use a vasodilator, such
as a nitrate (often combined with hydralazine to preserve the
generated nitric oxide) (13) and a purer beta-blocker to
obtain the same effect. The latter combination would have
the benefit of separate titration to optimal doses of the
vasodilator and beta-blocker and would also have the benefit
of additional antiremodeling properties of the nitrate (14).
In the meantime, however, the experience with carvedilol in
COPERNICUS suggests that it is safe and effective in this
patient population.
Reprint requests and correspondence: Dr. Jay N. Cohn, Cardiovascular Division, Mayo Mail Code 508, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis,
Minnesota 55455. E-mail: [email protected].
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Cohn
Editorial Comment
1431
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