Prerenal Azotemia in Congestive Heart Failure
University of California San Diego, San Diego, Calif., USA.Contributions to nephrology (Impact Factor: 1.8). 04/2010; 164:79-87. DOI: 10.1159/000313723
Prerenal failure is used to designate a reversible form of acute renal dysfunction. However, the terminology encompasses different conditions that vary considerably. The Acute Kidney Injury Network group has recently standardized the acute kidney injury (AKI) definition and classification system; however, these criteria have not determined specific diagnostic criteria to classify prerenal conditions. The difference in the pathophysiology and manifestations of prerenal failure suggests that our current approach needs to be revaluated. Several mechanisms are recognized as contributory to development of a prerenal state associated with cardiac failure. Because of the broad differences in patients' reserve capacity and functional status, prerenal states may be triggered at different time points during the course of the disease. Prerenal state needs to be classified depending on the underlying capacity for compensation, the nature, timing of the insult and the adaptation to chronic comorbidities. Current diagnosis of prerenal conditions is relatively insensitive and would benefit from additional research to define and classify the condition. Identification of high-risk states and high-risk processes associated with the use of new biomarkers for AKI will provide new tools to distinguish between the prerenal and established AKI. Achieving a consensus definition for prerenal syndrome will allow physicians to describe treatments and interventions as well as conduct and compare epidemiological studies in order to better describe the implications of this syndrome.
Fluid Overload: Diagnosis and Management
This book has been made possible by an unrestricted grant provided by Bellco s.r.l.
Contributions to Nephrology
Claudio Ronco Vicenza
Diagnosis and Management
Claudio Ronco Vicenza
Maria Rosa Costanzo Naperville, Ill.
Rinaldo Bellomo Melbourne, Vic.
Alan S. Maisel San Diego, Calif.
29 figures, and 25 tables, 2010
Basel · Freiburg · Paris · London · New York · Bangalore ·
Bangkok · Shanghai · Singapore · Tokyo · Sydney
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and Index
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view of ongoing research, changes in government regulations, and the constant flow of information relating to
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recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any
form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any
information storage and retrieval system, without permission in writing from the publisher.
© Copyright 2010 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel
Library of Congress Cataloging-in-Publication Data
Fluid overload : diagnosis and management / volume editors, Claudio Ronco
. . . [et al.].
p. ; cm. -- (Contributions to nephrology, ISSN 0302-5144 ; vol. 164)
Includes bibliographical references and index.
ISBN 978-3-8055-9416-5 (hard cover : alk. paper)
1. Body fluid disorders. 2. Congestive heart failure--Complications. I.
Ronco, C. (Claudio), 1951- II. Series: Contributions to nephrology, vol.
164. 0302-5144 ;
[DNLM: 1. Heart Failure. 2. Body Fluids. 3. Kidney Failure, Acute. 4.
Oliguria. 5. Water-Electrolyte Balance. W1 CO778UN v.164 2010 / WG 370
Department of Nephrology
Dialysis & Transplantation
International Renal Research Institute
San Bortolo Hospital
I-36100 Vicenza (Italy)
Department of Intensive Care
Melbourne, Vic. 3084 (Australia)
Maria Rosa Costanzo
Edward Heart Hospital
801 South Washington Street
Naperville, IL 60566 (USA)
Alan S. Maisel
VAMC Cardiology 111-A
3350 La Jolla Village Drive
San Diego, CA 921161 (USA)
Contributions to Nephrology
(Founded 1975 by Geoffrey M. Berlyne)
Ronco, C. (Vicenza); Costanzo, M.R. (Naperville, Ill.); Bellomo, R. (Melbourne, Vic.);
Maisel, A.S. (San Diego, Calif.)
Definition and Classification
1 Heart Failure: Pathophysiology and Clinical Picture
Palazzuoli, A.; Nuti, R. (Siena)
11 Heart Failure Classifications – Guidelines
Jankowska, E.A.; Ponikowski, P. (Wroclaw)
24 Acute Kidney Injury: Classification and Staging
Cruz, D.N. (Vicenza); Bagshaw, S.M. (Edmonton, Alta.); Ronco, C. (Vicenza);
Ricci, Z. (Rome)
33 Cardiorenal Syndromes: Definition and Classification
Ronco, C. (Vicenza)
39 Oliguria and Fluid Overload
Rimmelé, T.; Kellum, J.A. (Pittsburgh, Pa.)
46 Pathophysiology of Fluid Retention in Heart Failure
Chaney, E.; Shaw, A. (Durham, N.C.)
54 Fluid Overload as a Biomarker of Heart Failure and Acute Kidney Injury
Bagshaw, S.M. (Edmonton, Alta.); Cruz, D.N. (Vicenza)
69 Fluid Balance Issues in the Critically Ill Patient
Bouchard, J. (Montréal, Qué.); Mehta, R.L. (San Diego, Calif.)
79 Prerenal Azotemia in Congestive Heart Failure
Macedo, E.; Mehta, R. (San Diego, Calif.)
88 Use of Biomarkers in Evaluation of Patients with Heart Failure
Slavin, L.; Daniels, L.B.; Maisel, A.S. (San Diego, Calif.)
118 Oliguria, Creatinine and Other Biomarkers of Acute Kidney Injury
Ronco, C.; Grammaticopoulos, S. (Vicenza); Rosner, M. (Charlottesville, Va.);
De Cal, M.; Soni, S.; Lentini, P.; Piccinni, P. (Vicenza)
128 Current Techniques of Fluid Status Assessment
Peacock, W.F.; Soto, K.M. (Cleveland, Ohio)
143 Bioelectric Impedance Measurement for Fluid Status Assessment
Piccoli, A. (Padova)
153 Diuretic Therapy in Fluid-Overloaded and Heart Failure Patients
Bellomo, R.; Prowle, J.R.; Echeverri, J.E. (Melbourne, Vic.)
164 Pharmacological Therapy of Cardiorenal Syndromes and Heart Failure
House, A.A. (London, Ont.)
173 Extracorporeal Fluid Removal in Heart Failure Patients
Costanzo, M.R. (Naperville, Ill.); Agostoni, P.; Marenzi, G. (Milan)
199 Technical Aspects of Extracorporeal Ultrafiltration: Mechanisms,
Monitoring and Dedicated Technology
Nalesso, F.; Garzotto, F.; Ronco, C. (Vicenza)
209 Use of Brain Natriuretic Peptide and Bioimpedance to Guide Therapy
in Heart Failure Patients
Valle, R. (Chioggia); Aspromonte, N. (Rome)
217 Fluid Management in Pediatric Intensive Care
Favia, I.; Garisto, C.; Rossi, E.; Picardo, S., Ricci, Z. (Rome)
227 Fluid Assessment and Management in the Emergency Department
Di Somma, S.; Gori, C.S.; Grandi, T.; Risicato, M.G.; Salvatori, E. (Rome)
237 Author Index
238 Subject Index
The condition of fluid overload is often observed in patients with heart failure
and secondary oliguric states. In those conditions, a thorough assessment of
the fluid status of the patient may help guide the therapy and prevent compli-
cations induced by inappropriate therapeutic strategies. For these reasons, it
seems appropriate to collect a series of contributions in which the reader can
start with the information relevant to the type of syndromes involved in the
observed clinical picture, to progress subsequently towards the pathophysi-
ologic foundations of such syndromes, to further advance in the analysis of
diagnostic criteria and to finally conclude with the available therapeutic strate-
gies. The present book represents a practical tool for physicians and profes-
sionals involved in the management and care of patients with combined heart
and kidney disorders. It may also represent a reference textbook for medical
students, residents and fellows dealing in everyday practice with fluid over-
loaded and oliguric patients. The book is an important source of information
about new emerging diagnosting tools, therapies and technologies devoted to
the treatment of patients with severe fluid-related disorders. Different condi-
tions leading to fluid overload are described together with the possible diag-
nostic approaches and the therapeutic strategies. Various types of cardiorenal
syndrome are discussed in detail with information concerning pathophysiol-
ogy, biomarkers, pharmacological treatment and extracorporeal support. New
definitions for heart failure, acute kidney injury and cardiorenal syndromes
are reported to facilitate the reader in the process of understanding the com-
plex link between the heart and the kidney.
The delicate concept of fluid balance is discussed with specific attention to
the different components involved in the final composition of the body. Body
hydration status is of remarkable importance, and bioimpedance vector analysis
together with other techniques for the assessment of fluid status is discussed
in depth. Pharmacological therapies together with extracorporeal treatments
are presented in detail with special emphasis on critical care, cardiology, neph-
rology and emergency department populations. Pediatric populations are also
taken into consideration.
The technology for extracorporeal ultrafiltration is described in detail,
allowing the readers to appreciate the importance of this therapeutic approach
in refractory oliguric states. The simplicity and effectiveness of modern equip-
ment can make ultrafiltration a treatment easy to apply and safe to perform.
Additional support to safety can be offered by chemical biomarkers, on-line
blood volume monitoring and sequential bioimpedance determinations.
Based on all these considerations, the creation of a book covering all the
important issues in the field as well as the available technology and methods
represents an important project and a significant educational effort. We think
that a book on this subject will constitute an important contribution in the field
of cardiology and nephrology and may be particularly suited for being included
in the series Contributions to Nephrology.
We are indebted to BELLCO who provided an unrestricted grant for the
publication of the volume and to Karger for the professional editorial assistance
and the usual quality of printing.
Claudio Ronco, Vicenza
Maria Rosa Costanzo, Naperville, Ill.
Rinaldo Bellomo, Melbourne, Vic.
Alan S. Maisel, San Diego, Calif.
Definition and Classification
Ronco C, Costanzo MR, Bellomo R, Maisel AS (eds): Fluid Overload: Diagnosis and Management.
Contrib Nephrol. Basel, Karger, 2010, vol 164, pp 1–10
Heart Failure: Pathophysiology and
Alberto Palazzuoli ⭈ Ranuccio Nuti
Department of Internal Medicine and Metabolic Diseases, Cardiology Section, S. Maria alle Scotte
Hospital, University of Siena, Siena, Italy
Despite its high prevalence and significant rates of associated morbidity and mortality,
the syndrome of decompensated heart failure (HF) remains poorly defined and vastly
understudied. HF is due to several mechanisms including pump dysfunction disorder,
neurohormonal activation disorder, and salt-water retention disorder. The first step of the
syndrome includes cardiac damage and remodeling in terms of coronary disease systo
diastolic dysfunction and myocardial metabolism alterations. Neurohormonal activation
and hydrosaline retention occur during successive steps in response to cardiac injury for
compensatory reasons. Both mechanisms provide inotropic support to the failing heart
increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial per-
fusion pressure. However, they are deleterious to cardiocirculatory homeostasis in the late
stage. Further factors involve structural changes, such as loss of myofilaments, apoptosis
and disorganization of the cytoskeleton, as well as disturbances in Ca homeostasis, altera-
tion in receptor density, signal transduction, and collagen synthesis. Each disorder con-
tributes at a different time to HF development and worsening. Clinical presentation
depends on pulmonary congestion, organ perfusion, presence of coronary disease, fluid
retention and systemic pressure. For these reasons, the picture of HF is widely varied.
Copyright © 2010 S. Karger AG, Basel
Heart failure (HF) is the leading cause of hospital admissions in the Medicare
population. In addition to its high prevalence, hospitalization for decompen-
sated HF is associated with extraordinarily high rates of morbidity and mor-
tality. Estimates of the risk of death or rehospitalization within 60 days of
admission for this disease vary from 30 to 60%, depending on the population
studied in the US [1, 2]. Despite its high prevalence and significant rates of asso-
ciated morbidity and mortality, its pathophysiologic mechanisms and treatment
options remain poorly defined and vastly understudied. In addition, there is no
2 Palazzuoli · Nuti
consensus definition of the clinical problem that HF syndromes presents, no
accepted nomenclature to describe its clinical features, and no recognized clas-
sification scheme for its patient population .
HF should be defined as a clinical syndrome that develops in response to an
insult resulting in a decline of the pump and release capacity of the heart. This
is subsequently characterized by the continuous interaction between the under-
lying myocardial dysfunction and the compensatory neurohormonal mecha-
nisms that are activated. During the last 30 years, physicians have viewed HF
primarily as hemodynamic and edematous disorder, in which fluid retention
occurs because the heart cannot pump adequate quantities of blood to the kid-
neys. This conceptual model led to the successful utilization of diuretics for HF,
but it failed to obtain an outcome improvement. More recently, a new concept
regarding neurohormonal overdrive has been proposed and demonstrated: HF
develops and progresses because endogenous neurohormonal systems that are
activated by the initial injury to the heart exert a deleterious effect on the circu-
lation. Both hemodynamic and neurohormonal mechanisms help during early
stages of the inotropic state, but when sustained for long periods, their ability to
augment cardiac contractility wanes, and, instead, these same mechanisms act
to enhance ventricular wall stress, thereby impairing ventricular performance.
As the heart failure state evolves, endogenous mechanisms that are normally
activated to control wall stress become exhausted, and peripheral vasoconstric-
tion and sodium retention occur . Unopposed activation of hemodynamic
stresses and neurohormonal systems leads to further destruction of the myocar-
dium and progression of the underlying disease. The acceptance of this hemo-
dynamic-neurohormonal model has led to the development of vasodilators and
neurohormonal antagonists that have been shown to be useful alone or when
added to diuretics in the treatment of HF . Several ‘actors’ could contrib-
ute to HF development and impairment. To simplify the problem, we would
divide them into three principal disorders: pump dysfunction disorder, neuro-
hormonal activation disorder, and salt-water retention disorder.
Pump Dysfunction and Cardiac Remodeling
HF syndrome is primary characterized by cardiac cell loss due to myocardial
necrosis and ischemia with inotropic function reduction, peripheral vasocon-
striction reduction of tissue perfusion, afterload and preload increase, and further
cardiac function impairment. This represents, in brief, the mostly accepted hemo-
dynamic theory in the 1970–1980s. Behind the pump function incapacity, several
cellular, biochemical, and metabolic mechanisms exist. In patients with coronary
artery disease (CAD), acute myocardial infarction leads to loss of contractile tissue
with the development of both replacement and interstitial fibrosis . However,
HF in the setting of CAD is itself a heterogeneous condition, with many possible
HF: Pathophysiology and Clinical Picture 3
factors contributing to left ventricular (LV) dysfunction. Eventually, LV remodel-
ing and severe myocardial dysfunction ensues, and the clinical syndrome of HF
is fully expressed. The mechanisms whereby LV hypertrophy progresses to overt
HF are highly complex and not well understood. Structural abnormalities of the
heart, including cardiomyocyte and cytoskeletal abnormalities, as well as intersti-
tial fibrosis, may contribute importantly to chamber dysfunction. Hypertrophy,
often a response to pressure overload, may initially manifest itself as diastolic HF;
there is then emergence of abnormal LV filling. A hypertrophied ventricle is a stiff
chamber that fails to relax completely, leading to elevated LV filling pressures .
So-called ‘diastolic HF’ occurs more commonly in the elderly, in women, and in
patients with a long-standing history of systemic hypertension. Tissue damage
in HF is also characterized by activation of specific myocardial collagenases or
matrix metalloproteinases that are activated in response to a number of signals,
including alteration of the myocardial tissue and oxidative stress state [8, 9]. These
collagenases are likely responsible for disruption of the collagen strut network
that normally weaves the cardiac myocytes together. The net result of cardiac
matrix metalloproteinase activation is loss of the normal interstitial supporting
structure. When LV wall stress and strain are heightened as a result of changes in
LV geometric size and shape, there may be slippage of myocytes away from each
other, leading to further distortions in LV shape and size . The proportional
importance of myocyte slippage in the progression of the remodeling process is
still not clear and remains debated. It is well known that cardiac mass is increased
in patients with HF. This appears to be the result of a combination of reactive fibro-
sis and myocyte hypertrophy, along with altered cytoskeletal structure within the
cardiomyocyte . The abnormal growth of the heart undoubtedly contributes
to increased stiffness of the various chambers. Mechanical deformation of the
myocyte cell membrane, as might occur during progressively increased LV filling
pressure, is linked to early gene expression, protein synthesis, and enlargement
of cardiac myocytes. In addition to mechanical signals, neuroendocrine factors,
including angiotensin II, norepinephrine and endothelin, are associated with an
increase in myocyte size and cardiac hypertrophy. Cytokines and tumor necrosis
factor are both overexpressed in HF and further increase both hypertrophy and
During HF syndrome many Ca metabolism alterations have been well demon-
strated: free intracellular Ca increase during the rest phase, Ca reduction during
repolarization phase and Ca reuptake deficit from the sarcoplasmic reticulum.
Therefore, most of these processes are modulated by ATP disposal that is reduced
during HF. All these abnormalities lead to a dysfunction in excitation/contrac-
tion system with cardiac muscle incapacity to improve physiologically strength
contraction and elastic release . Failed myocardium reduces its energy
metabolism to keep an adequate perfusion and protect myocytes from imbal-
ance between energy request and production. Troponin release during HF desta-
bilization can reflect both myocyte loss for ischemia and apoptosis. Because of
4 Palazzuoli · Nuti
neurohormonal and inflammatory activation with oxidative stress increase, car-
diac cells could initiate a programmed death with progressive functional tissue
decrease. Myocardial injury could also be due to classic coronary disease (CAD)
that is often associated with HF. In this case, myocardial damage may be related to
hemodynamic and/or neurohormonal abnormalities or the result of an ischemic
event (myocardial infarction). Injury may also be the consequence of a high LV
diastolic pressure, further activation of neurohormones, and/or inotropic stimu-
lation, resulting in a supply and demand mismatch (increased myocardial oxygen
demand and decreased coronary perfusion) . These conditions may precipi-
tate injury, particularly in patients with CAD, who often have hibernating and/or
ischemic myocardium. The convergence of myocyte hypertrophy, myocyte slip-
page, reactive and reparative fibrosis, cytoskeletal alterations, and apoptosis are
believed to ultimately modulate the size, shape, and stiffness of the heart, leading
to progressive remodeling and to the development of the syndrome of HF.
Activation of vasoactive neurohormonal systems – sympathetic nervous system
(SNS) and renin-angiotensin-aldosterone system (RAAS) during early stages
permits to maintain circulatory homeostasis. RAAS activation induces direct
systemic vasoconstriction and activates other systems (arginine vasopressin –
AVP, aldosterone) that contribute to maintaining adequate intravascular volume.
However, chronic activation of these systems can have deleterious effects on car-
diac function and contributes to the progression of CHF . The activity of the
RAAS is central to the maintenance of water and electrolyte balance and blood
volume. The enzyme renin is released primarily by the juxtaglomerular cells of
the kidney in response to the activity of the SNS, changes in renal perfusion pres-
sure, reduced sodium absorption by the distal renal tubules, or AVP release .
Renin converts a precursor molecule (angiotensinogen) to angiotensin I, which
is then converted by ACE to angiotensin II. Angiotensin II produces vasocon-
striction and stimulation of aldosterone from the adrenal cortex, which increases
sodium ion reabsorption by the distal renal tubules . Angiotensin II also
modulates the thirst center. The production of angiotensin II by renin and ACE
takes place systemically in plasma and also within specific tissues, including the
brain, heart, and blood vessels. In acute CHF, the decrease in renal blood flow,
caused by progressive CHF, activates the RAAS. This increase in RAAS activ-
ity contributes to systemic vascular resistance. The increased vasoconstriction
resulting from RAAS activation results in increased LV afterload. This, in turn,
increases myocardial demand, LV end-diastolic pressure, pulmonary capillary
wedge pressure, and pulmonary congestion while decreasing cardiac output.
Angiotensin also promotes inflammatory pathways with TNF and interleu-
kin overexpression, tissue remodeling with vascular cell growth and increase in
HF: Pathophysiology and Clinical Picture 5
growth factors, endothelial dysfunction by nitric oxide reduction and platelet
aggregation, and oxidative stress by induction of reactive oxygen species [15, 16].
Vascular remodeling and fluid overload are also potentiated by the SNS and AVP.
The increased intravascular volume induced by AVP-mediated reabsorption of
free water results in elevated intracardiac pressure as well as pulmonary conges-
tion and edema. Systemic vasoconstriction mediated by angiotensin II increases
LV afterload and can also directly induce cardiac myocyte necrosis and alter the
myocardial matrix structure. Counterregulatory mechanisms consisting of natri-
uretic peptides, nitric oxide, and prostaglandins are generally not adequate to
maintain cardiac function, systemic perfusion, or sodium balance. The end result
of RAAS activation in CHF is clinical deterioration and progressive LV dysfunc-
tion. It is well documented that the degree of neurohormonal activation is corre-
lated with severity of HF. RAAS promotes the SNS activity that in turn, increases
cardiac contractility and heart rate, increasing stroke volume and peripheral
vasoconstriction . However, the cardiac work increase leads to an accelera-
tion of disease progression. Activation of SNS has been attributed to withdrawal
of normal restraining influences and enhancement of excitatory inputs including
changes in: (1) peripheral baroreceptor and chemoreceptor reflexes; (2) chemi-
cal mediators that control sympathetic outflow; (3) central integratory sites. The
sympathetic hyperactivity observed in HF is closely related to abnormalities in
cardiovascular reflexes: the sympatho-inhibitory cardiovascular reflexes are sig-
nificantly suppressed, whereas the sympatho-excitatory reflexes, including the
cardiac sympathetic afferent reflex and the arterial chemoreceptor reflex, are aug-
mented . Sympathetic activation in the setting of impaired systolic function
reflects the net balance and interaction between appropriate reflex compensatory
responses to impaired systolic function and excitatory stimuli that elicit adren-
ergic responses in excess of homeostatic requirements. All these changes drive
towards an altered cardiac and vascular vasodilating capacity, renal arterial vaso-
constriction and kidney flow redistribution with increased sodium reabsorption.
The cardiac oxygen utilization and vascular resistance increase, β-receptor down-
regulation and sympatho-vagal imbalance occur .
If not stopped, the sympathetic activity becomes the principal reason of
impairment and mortality in the advanced stages of disease. The physiological
answer of the body to HF is ‘adrenergic defense’, which involves inotropic, chro-
notropic and vasoconstrictive reserves. Unfortunately, this ‘sword’ later becomes
deleterious to those who handle it (fig. 1).
Salt and Water Retention
Baroreflex activation is one of the principal alterations in HF; it is mediated by
several systems with hydro-saline retention activity (RAAS, SNS, aldosterone,
endothelin and vasopressin). In particular, augmented baroreceptorial sensibility
6 Palazzuoli · Nuti
occurs together with RAAS and adrenergic activity preceding vasopressin increase.
Vasopressin mediates its effects via adenylcyclase-dependent signaling in the renal
collecting ducts increasing water retention, which is accomplished by upregulation
of the aquaporin-2 water channels . This upregulation results in an increased
movement of water from the collecting ducts back into the plasma, increasing free
water reabsorption, which leads to further increase in water retention . This
effect, may contribute to volume expansion and hyponatremia, a common condi-
tion in moderate and severe CHF. AVP could potentially contribute directly and
indirectly to well-characterized load-dependent and load-independent mecha-
nisms that may aggravate progressive ventricular remodeling and failure, as well
as the expression of the clinical HF syndrome. Congestion, in particular, is a hall-
mark of decompensated or severe CHF, and the volume retention secondary to
excessive AVP secretion adds to the volume retention of sodium and water caused
by aldosterone and other renal mechanisms . Inflammatory activation may
have a role in HF by both contributing to vascular dysfunction and magnifying
fluid overload. The amount of fluid in the pulmonary interstitium and alveoli is
tightly controlled by an active process of reabsorption. Reduction in intrarenal
perfusion and the consequent fall in GFR lead to reflex activation of the RAAS
with tubular reclamation of salt and water. In addition, some of the neurohor-
monal and inflammatory activation, commonly observed in HF patients, prob-
ably also contributes to renal dysfunction. The result is kidney dysfunction with
hypoxic and vasoconstrictive injury which may also lead to tubular necrosis .
Besides, high renal venous pressure contributes to this vasomotor nephropathy
Increased cardiac work
and oxygen consum p tion
Reduced stroke volum e
and increased lling pre ssu re
Oxidative stre ss, vascular
and endothelial dam age
Peripheral vasoconstriction and
plasm a volum e expansion
Preload and post-load
RAAS, SN S, AVP,
in ammatory activation
Reduced renal blood ow
and renal function
Worsen ing HF, hem odynam ic and
Fig. 1. Neurohormonal activation in HF.
HF: Pathophysiology and Clinical Picture 7
and further amplifies renal dysfunction. Progressive renal dysfunction, by induc-
ing salt and fluid retention, stimulates the HF process inducing an important
vicious cycle to HF exacerbation. Fluid overload is also caused by fluid redistri-
bution rather than by fluid accumulation. Increased vascular resistance/stiffness
may lead to both reduced capacitance in the large veins together with increased
arterial resistance. The decrease in capacitance in large veins will lead to increased
venous return and heightened preload . This could explain the mechanism of
fluid redistribution in specific district (lung) rather than fluid overload in periph-
eral organs during HF worsening.
The clinical picture of HF is widely varied. The most common classification is
based on the initial clinical presentation; it makes a distinction between new
onset acute HF, and transient and chronic CHF. Clinical presentation can
depend on hemodynamic status, primary cardiac disorder, systemic pressure
and organ perfusion/damage. Classical definition and classification divide HF
syndrome into pulmonary edema, right HF, HF with acute coronary syndrome,
hypertensive HF, and cardiogenic shock .
Another distinction is about the type of LV dysfunction: most patients with
HF have both systolic and diastolic LV dysfunction, but in some cases the syn-
drome can occur with isolated systolic or diastolic dysfunction. HF with pre-
served left ventricular ejection fraction (LVEF) is characterized by a non dilated,
usually hypertrophied left ventricle in which LVEF is preserved at rest, and the
parameters of LV relaxation and filling are markedly deranged. Patients with pre-
served LVEF and HF are a heterogeneous and understudied group that includes
those with both hypertensive heart disease and hypertrophic cardiomyopathy.
Epidemiologic data regarding the proportion of patients hospitalized with dec-
ompensated HF who have preserved LVEF demonstrate that almost half of all
HF patients have preserved LVEF, and mortality rates were similar between
those with preserved and those with impaired ejection fraction (EF) .
The categorization of patients with decompensated HF by hemodynamic pro-
files has been proposed; it classifies patients as either ‘wet’ or ‘dry’, ‘warm’ or ‘cold’,
and addresses the two primary hemodynamic derangements in HF: elevated fill-
ing pressures and organ perfusion damage. The differentiation between the ‘wet’
and ‘dry’ patient with decompensated HF can usually be made at the bedside; a
bedside evaluation, however, may require that great care be taken to identify vol-
ume overload in some patients with ‘occult’ excess fluid [27, 28] (fig. 2).
More recently, a new simple classification taking into consideration etiology,
LV defect, and presentation has been proposed: patients may be classified into
HF presenting for the first time (de novo) or worsening chronic HF. In both
groups, the presence and extent of CAD may determine the initial, in-hospital,
8 Palazzuoli · Nuti
and postdischarge management. The EF may influence postdischarge rather than
initial management, which should be based on the presenting clinical profile.
Several associated clinical conditions such as low blood pressure, renal impair-
ment, and/or signs and symptoms refractory to standard therapy characterize
advanced HF  (table 1). De novo HF represents the remainder of AHF, and
may be further divided into those with preexisting risk for HF (e.g. hypertension,
CAD) without evidence of prior LV dysfunction or structural abnormalities and
those with preexisting cardiac structural abnormalities (e.g. reduced EF).
HF is a clinical syndrome characterized by the continuous interaction between
the myocardial dysfunction and the compensatory neurohormonal mechanisms
that are activated. Many ‘actors’ including myocardial dysfunction, RAAS, SNS,
vasopressin and inflammatory systems contribute to HF development and
Clinical presentation differs in relation to hemodynamic status, primary car-
diac disorder, systemic pressure and organ perfusion/damage. For this reason,
Right HF Hypertension
Systolic HF Diastolic HF
High or low LV
High or low systemic
High sodium water
Low sodium water
Fig. 2. HF presentations: there are many types of HF with different clinical aspects and
outcome on the basis of structural heart disease.
HF: Pathophysiology and Clinical Picture 9
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Palazzuoli Alberto, MD, PhD
Department of Internal Medicine and Metabolic Diseases, Cardiology Section
S. Maria alle Scotte Hospital, University of Siena
I–53100 Siena (Italy)
Tel. +39 577585363, Fax +39 577233480, E-Mail email@example.com
Definition and Classification
Ronco C, Costanzo MR, Bellomo R, Maisel AS (eds): Fluid Overload: Diagnosis and Management.
Contrib Nephrol. Basel, Karger, 2010, vol 164, pp 11–23
Heart Failure Classifications – Guidelines
Ewa A. Jankowska ⭈ Piotr Ponikowski
Department of Heart Diseases, Wroclaw Medical University, and Centre for Heart Diseases, Military
Hospital, Wroclaw, Poland
The clinical syndrome of heart failure is hugely heterogeneous. In this chapter, the authors
discuss several distinct classifications of this syndrome that have been developed in order
to better characterize an individual case and subsequently apply an optimal manage-
ment. Classifications are based on the time course of the clinical presentation of heart
failure, severity of symptoms and signs of heart failure, structural changes within the
heart, predominant etiology and comorbidities.
Copyright © 2010 S. Karger AG, Basel
It has always been difficult to propose a widely acceptable definition of the ‘syn-
drome of heart failure’ precisely describing the complex nature and essential
principles of the disease, which could be unanimously acceptable by clinical
scientists, epidemiologists and physicians, and at the same time be easily appli-
cable in everyday clinical practice. In the recent decades, the definition of heart
failure (HF) has evolved along with the revolutionary progress in the under-
standing of the pathophysiology and mechanisms underlying cardinal signs
and symptoms of this syndrome . Current approach is to base the definition
on the coexistence of three distinct elements: abnormal heart structure and/or
function with signs and symptoms of the disease. Such a definition was initially
proposed in 1995 by the first European Society of Cardiology (ESC) guidelines
 and remained virtually unchanged until today .
According to the most recent ESC guidelines , HF is defined as a clinical
syndrome when all the following conditions are fulfilled:
1 Presence of typical HF symptoms (breathlessness at rest or on exercise,
fatigue, tiredness, ankle swelling);
2 Presence of typical HF signs (tachycardia, tachypnea, pulmonary rales,
pleural effusion, raised jugular venous pressure, peripheral edema, hepato-
12 Jankowska · Ponikowski
3 Objective evidence of an abnormal structure or/and function of the heart at
rest (cardiomegaly, third heart sound, cardiac murmurs, abnormality on the
echocardiogram, raised natriuretic peptide concentration).
In principle, the American College of Cardiology (ACC)/American Heart
Association (AHA) definition is practically identical, describing HF as ‘a com-
plex clinical syndrome that can result from any structural or functional cardiac
disorder that impairs the ability of the ventricle to fill with or eject blood. The
cardinal manifestations of HF are dyspnea and fatigue, which may limit exercise
tolerance, and fluid retention, which may lead to pulmonary congestion and
peripheral edema’ [4, 5].
Thus, the diagnosis of HF should be always based on a careful clinical history,
physical examination and subsequent investigations, among which echocar-
diography and assessment of circulating natriuretic peptides play a major role.
Clinical improvement as a response to treatment directed at HF (being an
element of the original ESC definition of HF ) is no longer sufficient for the
diagnosis, but may be helpful in some circumstances. It is emphasized that an
etiology of the heart disease underlying HF should be an obligatory element of
the final diagnosis.
The clinical syndrome of HF is hugely heterogeneous. Several distinct clas-
sifications of this syndrome have been proposed in order to better characterize
an individual case and subsequently apply an optimal management. They will
be discussed in this chapter.
Time Course of the Clinical Presentation of Heart Failure
Based on the time course of the clinical presentation of HF, the heart disease can
be classified as: (a) new onset HF (the first presentation of symptoms and signs,
with the acute or slow onset); (b) transient HF (recurrent or episodic symptoms
and signs, over a limited time period, although long-term treatment may be
indicated); (c) chronic HF (persistent symptoms and signs; can be stable, wors-
ening or decompensated).
This classification has been originally introduced in the recent ESC guide-
Classifications Based on the Severity of Heart Failure Symptoms and
Structural Changes within the Heart
Shortness of breath and/or fatigue (either during exercise or at rest) are typi-
cal and cardinal symptoms of HF. However, they are subjective, nonspecific for
HF, and the clinical presentation may be difficult to distinguish from numerous
noncardiac disorders such as chronic obstructive pulmonary disease, obesity,
HF Classifications – Guidelines 13
depression, cognitive disorders, normal aging. Ideally, they should be assessed
with standardized methods (e.g. validated and reproducible scales  or differ-
ent forms of exercise testing).
Paroxysmal nocturnal dyspnea and orthopnea can also occur in HF patients
and may precede pulmonary edema by several days and coexist with elevated fil-
ing pressure of the left ventricle. Orthopnea can be tested by putting the patient
in the supine position for a defined period of time while monitoring the devel-
opment of dyspnea. Supine positioning mobilizes fluid from dependent venous
reservoirs in the abdomen and the lower extremities, which increases venous
return to the thoracic compartment. It should be also remembered that at the
later stage HF affects almost all body organs, and other subjective complaints
may dominate the clinical picture of HF.
Despite these potential drawbacks, symptoms are often used to classify
severity of HF, monitor therapy and evaluate prognosis. The New York Heart
Association (NYHA) functional classification (class I–IV) reflects HF severity
and is based on symptoms and exercise capacity (table 1) [7, 8]. The NYHA
functional classification has proved to be clinically useful, and is employed
routinely in most randomized clinical trials. HF patients in NYHA class I
should be distinguished from asymptomatic subjects with left ventricular (LV)
dysfunction. The former have objective evidence of cardiac dysfunction and
a past history of HF symptoms/signs that have entirely resolved due to HF
treatment, whereas the latter have never experienced the clinical syndrome
of HF. However, asymptomatic LV dysfunction carries a high risk of overt HF
Additionally, to describe clinical symptoms the terms mild, moderate, or
severe HF are used . Mild HF is used for subjects who can perform every-
day activities with no important limitations due to dyspnea or/and fatigue.
Severe HF is applied for those who are markedly severely symptomatic and
Table 1. NYHA functional classification of the severity of HF based on symptoms and
physical activity [7, 8], adapted in ESC guidelines 
Class I No limitation of physical activity. Ordinary physical activity does not
cause undue fatigue, palpitation, or dyspnea.
Class II Slight limitation of physical activity. Comfortable at rest, but ordinary
physical activity results in fatigue, palpitation, or dyspnea.
Class III Marked limitation of physical activity. Comfortable at rest, but less than
ordinary activity results in fatigue, palpitation, or dyspnea.
Class IV Unable to carry on any physical activity without discomfort. Symptoms at rest.
If any physical activity is undertaken, discomfort is increased.
14 Jankowska · Ponikowski
need frequent medical attention, whereas moderate HF is used for the remain-
Based on the objective measure of exercise intolerance derived from cardio-
pulmonary exercise testing (oxygen consumption at peak exercise or at anaero-
bic threshold), Weber  proposed the exercise functional classification (classes
A–D) of patients with HF (table 2).
The ACC/AHA guidelines [4, 5] recommend the classification of HF based
on the structural changes within the heart and symptoms (stages A–D; table 3).
It distinguishes four consecutive stages involved in the development and pro-
gression of HF syndrome. The first two stages (A and B) although not being HF
themselves allow to identify patients who are at risk for developing HF. Stage C
indicates patients with current or past symptomatic HF associated with under-
lying structural heart disease, whereas stage D denotes advanced structural
heart disease and marked-severe HF symptoms at rest despite maximal medical
therapy (and is often referred to as refractory HF – see below).
Over the last years, we have witnessed a revolutionary improvement in the
comprehensive management of HF syndrome, which has substantially changed
Table 2. Weber’s exercise functional classification of patients with HF based on the mea-
surement of oxygen consumption 
Class Peak/maximal oxygen
Oxygen consumption at
anaerobic threshold, ml/min/kg
A >20 >14
B 16–20 11–14
C 10–15 8–10
D <10 <8
Table 3. ACC/AHA stages of HF based on the structural changes within the heart and
symptoms [4, 5], adapted in ESC guidelines 
Stage A At high risk for developing HF. No identified structural or functional
abnormality; no signs or symptoms.
Stage B Developed structural heart disease that is strongly associated with the
development of HF, but without signs or symptoms.
Stage C Symptomatic HF associated with underlying structural heart disease.
Stage D Advanced structural heart disease and marked symptoms of HF at rest despite
maximal medical therapy.
HF Classifications – Guidelines 15
the clinical characteristics of these patients. There is a growing number of long-
term HF survivors who progress to the advanced stages of the disease, char-
acterized by severe symptoms, marked hemodynamic impairment, frequent
hospital admissions and very poor outcome. Thus, an emerging population of
patients with advanced chronic HF needs to be better identified and charac-
terized, which fully justifies a need for new classification. In the recent posi-
tion paper of the Study Group of Heart Failure Association of the ESC ,
advanced chronic HF was defined as: (a) severe symptoms of HF with dyspnea
and/or fatigue at rest or with minimal exertion (NYHA functional class III or
IV); (b) episodes of fluid retention and/or of reduced cardiac output at rest; (c)
objective evidence of severe cardiac dysfunction, at least 1 of the following: low
LV ejection fraction (LVEF ≤30%), a severe abnormality of cardiac function on
Doppler echocardiography (pseudonormal or restrictive mitral inflow pattern),
high LV filling pressures, high BNP or NT-proBNP plasma levels (absence of
noncardiac causes); (d) severe impairment of functional capacity, at least 1 of
the following: inability to exercise, 6-min walking distance <300 m, peak oxy-
gen consumption <12–14 ml/kg/min; (e) history of ≥1 HF hospitalization in
the past 6 months; (f) presence of all the previous features despite attempts to
optimize therapy according to the ESC guidelines.
The term advanced chronic HF comprises also cases traditionally labeled as
refractory HF and/or end-stage HF (fig. 1). The former term applies to patients
with stage D according to the ACC/AHA guidelines, where it is defined by the
presence of marked symptoms at rest despite maximal medical therapy. The
Advanced HF with no
chance of reversibility
Fig. 1. Conceptual presentation and differentiation between advanced, refractory and
end-stage HF according to Metra et al. .
16 Jankowska · Ponikowski
latter indicates an extremely advanced condition where no improvement with
conventional HF treatment is possible, and palliative care, ventricular assist
devices or heart transplantation are indicated . This condition should be
distinguished from advanced chronic HF, in which a certain degree of revers-
ibility may be present .
Classifications Based on Signs of Heart Failure
Typical signs of HF are those related to fluid retention (increase in body weight,
elevated jugular venous pressure, hepatojugular reflux, ascites, peripheral edema,
hepatomegaly, splenomegaly, rales, pulmonary congestion, pulmonary edema)
and/or peripheral hypoperfusion (low systemic blood pressure – BP, cyanosis,
prerenal renal failure, confusion, abdominal discomfort).
The assessment of HF symptoms (both congestion and hypoperfusion) are
the major clinical criteria applied in the Killip-Kimball classification (stages
Table 4. Killip-Kimball classification designed to provide a clinical estimate of the sever-
ity of circulatory derangement in the treatment of acute myocardial infarction ,
adapted in ESC guidelines for acute HF .
Stage I No HF. No clinical signs of cardiac decompensation.
Stage II HF. Diagnostic criteria include: rales, S3 gallop and pulmonary venous
hypertension. Pulmonary congestion with wet rales in the lower half
of the lung fields.
Stage III Severe HF. Frank pulmonary edema with rales throughout the lung fields.
Stage IV Cardiogenic shock. Signs include hypotension (systolic BP <90 mm Hg),
and evidence of peripheral vasoconstriction such as oliguria, cyanosis
Table 5. Forrester classification designed to describe clinical and hemodynamic status in
acute myocardial infarction , adapted in ESC guidelines for acute HF 
Group 1 Normal perfusion and pulmonary capillary wedge pressure (PCWP; an
estimate of left atrial pressure).
Group 2 Poor perfusion and low PCWP (hypovolemic status).
Group 3 Near-normal perfusion and high PCWP (pulmonary edema).
Group 4 Poor perfusion and high PCWP (cardiogenic shock).
HF Classifications – Guidelines 17
I–IV) for the risk stratification of patients with acute myocardial infarction
complicated by HF (table 4) .
Forrester et al.  proposed another classification, taking into account the
presence of peripheral hypoperfusion and pulmonary congestion on the basis of
the Swan-Ganz catheterization. The authors distinguished four hemodynamic
profiles, and the Forrester classification (groups 1–4) was originally designed for
patients with acute myocardial infarction (table 5). It has been recently demon-
strated that also in patients with HF similar hemodynamic profiles can be iden-
tified on the basis of careful physical examination and further used in clinical
practice for meaningful distinction of these patients [13, 14]. These clinical pro-
files can be defined by: (1) the absence or presence of signs of congestion (con-
gestion evidenced by a recent history of orthopnea and/or physical examination
evidence of jugular venous distention, rales, hepato-jugular reflux, ascites, periph-
eral edema, leftward radiation of the pulmonic heart sound, or a square wave BP
response to the Valsalva maneuver), and (2) the evidence suggesting adequate or
inadequate perfusion [hypoperfusion evidenced by presence of a narrow propor-
tional pulse pressure ([systolic – diastolic BP]/systolic BP <25%), pulsus alter-
nans, symptomatic hypotension (without orthostasis), cool extremities, and/or
impaired mentation; fig. 2]. Such profiles are easily assessed at the bedside and
provide useful prognostic information and may be of particular importance in
patients with advanced HF or those who developed decompensation.
Right and left HF are the other descriptive terms often used to classify HF,
and they refer to syndromes presenting predominantly with the congestion
of the systemic or pulmonary veins leading to signs of fluid retention with
peripheral edema, ascites, hepatomegaly or pulmonary edema, respectively.
Congestion at rest?
at rest ?
• D JVP
• Rales (often
by local factors
• Narrow PP (<25%)
• Cool extremities
• ACEI intolerance
• d Na, d GFR
Warm and dry
Warm and wet
Cold and wet
Cold and dry
Fig. 2. Clinical assessment of hemodynamic profile of acute HF based on the presence/
absence of congestion and low perfusion at rest [13, 14], adapted in ESC guidelines .
ACEI = Angiotensin-converting enzyme inhibitor; LVEDP = LV end-diastolic pressure; JVP
= jugular venous pressure; PP = pulse pressure.
18 Jankowska · Ponikowski
Less frequently, right and left HF may be related to the signs and symptoms of
hypoperfusion within pulmonary or systemic vascular beds, respectively .
Forward and backward HF are terms that can be used to emphasize the signs
and symptoms resulting from peripheral hypoperfusion or an increase in atrial
pressures with fluid congestion, respectively .
Heart Failure with Preserved and Reduced Ejection Fraction (Systolic and
Diastolic Heart Failure)
In the past, there was a clear distinction between systolic and diastolic HF, arbi-
trarily based on the cut-off value of LVEF. Patients with typical symptoms and/
or signs of HF and preserved LVEF (i.e. >45–50%) tended to be differentiated
from those with clinical picture of HF and reduced LVEF. It has a clear histori-
cal background as many clinical and epidemiological studies and clinical trials
included only HF patients with reduced LVEF.
Currently, there is a view that these pathologies should not be considered
as separate entities . In fact, the majority (almost all) of patients with the
clinical syndrome of HF have evidence of diastolic dysfunction assessed during
echocardiography, whereas only a subset of these subjects demonstrate reduced
LVEF (<40–45%) indicating impaired systolic function. Therefore, current
guidelines recommend distinguishing between systolic HF and HF with normal
ejection fraction or HF with preserved systolic function .
Echocardiography plays a major role in confirming the diagnosis of HFPEF.
The diagnosis of HFPEF requires three conditions to be fulfilled [3, 16]:
1 Presence of typical signs and symptoms of HF;
2 Confirmation of normal or only mildly abnormal LV systolic function (LVEF
3 Evidence of diastolic dysfunction based on echocardiography examina-
There are three major patterns of abnormal filling, indicating abnormal LV
relaxation and/or diastolic stiffness (abnormal relaxation, pseudonormaliza-
tion, restrictive filling) [3, 16]. A detailed description of echocardiographic
parameters reflecting diastolic function of LV has recently been provided in a
consensus paper from the Heart Failure Association of ESC .
Acute and Decompensated Heart Failure
The terms ‘acute’ or decompensated’ HF are often used, although there are no
commonly accepted definitions of these conditions. In most cases, these terms
reflect the clinical need to characterize patients who are acutely admitted to
hospital with signs and symptoms of HF.
HF Classifications – Guidelines 19
According to ESC guidelines , acute HF is defined as a rapid onset or a
gradual or rapid change in the symptoms and signs of HF, resulting in the need
for urgent therapy or/and hospitalization for relief of symptoms. Acute HF indi-
cates predominantly the medical emergency and the need for urgent therapy.
However, the dynamic changes in the signs and symptoms of HF also constitute
a crucial element of the clinical presentation in acute HF. Irrespective of the
precipitating factor, pulmonary and/or systemic congestion due to elevated ven-
tricular filling pressures, with or without a decrease in cardiac output, is nearly
a universal finding. Acute HF may present as new-onset HF, in those without
previous history of HF, or most frequently as decompensation in the presence
of chronic HF. The former after clinical stabilization often progresses to chronic
The classification of clinical presentations of acute HF according to ESC
guidelines  comprises the following clinical scenarios (some of them may
overlap each other): (a) worsening or decompensated chronic HF (peripheral
edema/congestion) – usually a progressive worsening of chronic HF, evidence
of systemic and/or pulmonary congestion; (b) pulmonary edema – severe
respiratory distress, tachypnea and orthopnea with rales over lungs, arterial O
saturation usually <90% on room air; (c) hypertensive HF – high systemic BP,
usually preserved LVEF, increased sympathetic drive with tachycardia and vaso-
constriction, patients may be euvolemic or only mildly hypervolemic and pres-
ent frequently with signs of pulmonary congestion without signs of systemic
congestion; (d) cardiogenic shock – evidence of tissue hypoperfusion induced
by HF after adequate correction of preload, reduced systolic BP (<90 mm Hg or
a drop in mean arterial pressure of >30 mm Hg) and absent or low urine output
(<0.5 ml/kg/h), evidence of organ hypoperfusion and pulmonary congestion
develop rapidly; (e) right HF – low output syndrome in the absence of pulmo-
nary congestion, with low left ventricle filling pressures, with increased jugular
venous pressure, with or without hepatomegaly; (f) HF in the course of acute
The other classification of clinical profiles of acute HF at presentation has
been recently proposed by Gheorghiade and Pang  and Gheorghiade et al.
: (a) elevated systolic BP (>160 mm Hg) – predominantly pulmonary (radio-
graphic/clinical) congestion, with or without systemic congestion, typically with
preserved LVEF, usually signs and symptoms develop abruptly; (b) normal or
moderately elevated systolic BP – signs and symptoms develop gradually (days
or weeks), associated with significant systemic congestion; (c) low systolic BP
(<90 mm Hg) – mostly related to low cardiac output and often associated with
impaired renal function; (d) cardiogenic shock – rapid onset, primarily compli-
cating acute myocardial infarction, fulminant myocarditis, acute valvular dis-
ease; (e) flash pulmonary edema – abrupt onset, often precipitated by severe
systemic hypertension; (f) acute coronary syndrome and acute HF – rapid or
gradual onset, in many cases signs and symptoms of HF resolve after resolution
20 Jankowska · Ponikowski
of ischemia; (g) isolated right HF – rapid or gradual onset due to primary or
secondary pulmonary artery hypertension or RV pathology (e.g. RV infarct),
no epidemiological data; (h) postcardiac surgery HF – rapid or gradual onset,
occurring in patients with or without previous ventricular dysfunction, often
related to worsening diastolic function and volume overload immediately after
surgery, can also be caused by intraoperative cardiac injury.
Another more simplified classification of acute HF into ‘vascular’ versus ‘car-
diac’ failure has also been proposed . The former often develops suddenly
and comprises those with elevated BP, predominantly pulmonary congestion,
preserved LVEF and rapid response to therapy. The latter develops gradually
(days or weeks) and is associated with normal BP, systemic congestion usually
on the background of chronic HF (table 6).
However, it should be noted that in the recent ACC/AHA guidelines  the
term ‘acute HF’ has not been introduced. Instead, the authors have referred to
a ‘hospitalized patient’ (clinical scenario when acute or progressive symptoms
of HF develop and require hospitalization) . Three distinct clinical profiles
characterizing such patients have been described : (a) volume overload –
manifested by pulmonary and/or systemic congestion, often precipitated by an
acute increase in chronic hypertension; (b) profound depression of cardiac out-
put – manifested by hypotension, impaired renal function, and/or a shock syn-
drome; (c) signs and symptoms of both fluid overload and shock.
Table 6. Clinical features distinguishing acute HF into ‘vascular’ and ‘cardiac’ failure 
Clinical features Vascular failure Cardiac failure
BP high normal
Worsening rapid gradual (days)
present systemic rather than pulmonary
PCWP acutely increased chronically high
Rales present may be absent
severe may be absent
Weight gain minimal significant (edema)
LVEF relatively preserved usually low
relatively rapid continue to have systemic congestion in