Page 226 - Basic _ Clinical Pharmacology ( PDFDrive )

13 Drugs Used in Heart
A
P
C
H
T
R
E

Failure

*
Bertram G. Katzung, MD, PhD

C ASE STUD Y

A 55-year-old man noticed shortness of breath with exer- Crackles are noted at both lung bases, and his jugular
tion while on a camping vacation in a national park. He has venous pressure is elevated. The liver is enlarged, and there
a 15-year history of poorly controlled hypertension. The is 3+ edema of the ankles and feet. An echocardiogram
shortness of breath was accompanied by onset of swelling shows an enlarged, poorly contracting heart with a left ven-
of the feet and ankles and increasing fatigue. On physical tricular ejection fraction of about 30% (normal: 60%). The
examination in the clinic, he is found to be mildly short of presumptive diagnosis is stage C, class III heart failure with
breath lying down but feels better sitting upright. Pulse is reduced ejection fraction. What treatment is indicated?
100 bpm and regular, and blood pressure is 165/100 mm Hg.

Heart failure occurs when cardiac output is inadequate to provide Heart failure is a progressive disease that is characterized by a
the oxygen needed by the body. It is a highly lethal condition, gradual reduction in cardiac performance, punctuated in many
with a 5-year mortality rate conventionally said to be about 50%. patients by episodes of acute decompensation, often requiring
The most common cause of heart failure in the USA is coronary hospitalization. Treatment is therefore directed at two somewhat
artery disease, with hypertension also an important factor. Two different goals: (1) reducing symptoms and slowing progression as
major types of failure may be distinguished. Approximately 50% much as possible during relatively stable periods and (2) managing
of younger patients have systolic failure, with reduced mechani- acute episodes of decompensated failure. These factors are dis-
cal pumping action (contractility) and reduced ejection fraction cussed in Clinical Pharmacology of Drugs Used in Heart Failure.
(HFrEF). The remaining group has diastolic failure, with stiffen- Although it is believed that the primary defect in early sys-
ing and loss of adequate relaxation playing a major role in reduc- tolic heart failure resides in the excitation-contraction coupling
ing filling and cardiac output. Ejection fraction may be normal machinery of the myocardium, the clinical condition also involves
(preserved, HFpEF) in diastolic failure even though stroke volume many other processes and organs, including the baroreceptor
is significantly reduced. The proportion of patients with diastolic reflex, the sympathetic nervous system, the kidneys, angiotensin
failure increases with age. Because other cardiovascular conditions II and other peptides, aldosterone, and apoptosis of cardiac cells.
(especially myocardial infarction) are now being treated more effec- Recognition of these factors has resulted in evolution of a variety
tively, more patients are surviving long enough for heart failure to of drug treatment strategies (Table 13–1) that constitute the
develop, making heart failure one of the cardiovascular conditions current standard of care.
that is actually increasing in prevalence in some countries. Large clinical trials have shown that therapy directed at non-
cardiac targets is more valuable in the long-term treatment of
heart failure than traditional positive inotropic agents (cardiac
* The author thanks Dr. William W. Parmley, MD, coauthor of this chapter glycosides [digitalis]). Large trials have also shown that angiotensin-
in prior editions. converting enzyme (ACE) inhibitors, angiotensin receptor
212