CHAPTER 22 - Pathophysiology of Heart Failure from Libby: Braunwald... http://remoto.dgb.uanl.mx:2065/das/book/body/108023714-4/0/1549/152...

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Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed.

Copyright © 2007 Saunders, An Imprint of Elsevier

CHAPTER 22 – Pathophysiology of Heart Failure

Douglas L. Mann

Overview, 541
Pathogenesis, 541
Heart Failure as a Progressive Model, 541
Neurohormonal Mechanisms, 541
Activation of the Sympathetic Nervous System, 542
Activation of the Renin-Angiotensin System, 542
Neurohormonal Alterations of Renal Function, 544
Neurohormonal Alterations in the Peripheral Vasculature,
547

Left Ventricular Remodeling, 549

Alterations in Cardiac Myocyte Biology, 549
Alterations in the Myocardium, 553
Alterations in the Left Ventricular Structure, 557

Reversibility of Left Ventricular Remodeling (Myocardial Recovery), 559

Future Directions, 559
References, 560
OVERVIEW
Despite repeated attempts to develop a unifying hypothesis that describes the clinical syndrome of heart failure (HF), no
single conceptual paradigm has withstood the test of time. Thus it is not surprising that clinicians and investigators have
used a variety of increasingly complex model systems in an attempt to describe the syndrome of HF. Although clinicians
initially viewed HF as a problem of excessive salt and water retention that was caused by abnormalities of renal blood
flow (the “cardiorenal model” [1] ), as they began to perform careful hemodynamic measurements, it also became
apparent that HF was associated with a reduced cardiac output and excessive peripheral vasoconstriction. This latter
realization led to the development of the “cardiocirculatory” or “hemodynamic” model for HF, [1] wherein HF was thought
to arise largely as a result of abnormalities of the pumping capacity of the heart and excessive peripheral
vasoconstriction. However, although both the cardiorenal and cardiocirculatory models for HF explained the excessive
salt and water retention that HF patients experience, neither of these models explained the relentless “disease
progression” that occurs in this syndrome. Indeed, although the cardiorenal models provided the rational basis for the use
of diuretics to control the volume status of patients with HF, and the cardiocirculatory model provided the rational basis
for the use of inotropes and intravenous vasodilators to augment cardiac output, these therapeutic strategies have not
prevented HF from progressing, nor have they led to prolonged life for patients with moderate to severe HF.

On the basis of these arguments, it has become increasingly apparent that HF can no longer be defined in simple
hemodynamic terms. Accordingly, in this chapter we focus on the molecular and cellular changes that underlie HF with
depressed systolic function, with an emphasis on the role of neurohormonal activation and left ventricular (LV) remodeling
as the primary determinants for disease progression in HF. The hemodynamic, contractile, and wall motion disorders in
systolic HF are discussed in the chapters on echocardiography (see Chap 14 ), cardiac catheterization (see Chap 19 ),
radionuclide imaging (see Chap 16 ), and the clinical assessment of the patients with HF (see Chap 23 ). The
pathogenesis of HF with a normal ejection fraction is discussed elsewhere (see Chap 26 ).

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