TMJ - September 2002: Fluid Management in Heart Failure (“Optimising Monitoring”)

Heart failure is a complex clinical syndrome characterised by abnormalities of left ventricular dysfunction
(systolic and diastolic) and changes in neurohumoral regulation accompanied by effort intolerance, fluid
retention, poor tissue perfusion and decreased survival.1Heart failure is a progressive disorder. The goals
of treating heart failure are not only to improve symptoms and quality of life, but also to decrease the
likelihood of disease progression, decrease the risk of death, need for hospitalisation and attendant costs.
Early identification and appropriate treatment of patients are critical to achieve the greatest impact on
individuals and public health.2

PATHOPHYSIOLOGY OF FLUID RETENTION

Fluid retention impairs the functional capacity of patients with heart failure, but there is only a modest
relation between symptoms and peripheral oedema. Some patients with marked fluid retention have few
complaints whereas some patients, bedridden in NYHA Class IV, have no peripheral oedema with minimal
pulmonary rales.2

These discrepancies are related to differences among patients in ventricular distensibility, pulmonary
vascular resistance and mechanics, right ventricular function, capillary permeability, regional blood flow,
skeletal muscle function.

1. Fluid retention is caused in part by reduction in glomerular filtration rate, activation of the
reninangiotensin-aldosterone system. Impaired hepatic function, owing to hepatic venous
congestion, reduced hepatic blood flow interfere with metabolism of aldosterone, further raising
its plasma concentration and augmenting the retention of sodium and water. 3
2. Ventricular filling pressures, atrial pressures, systemic and pulmonary venous pressures rise
abnormally. This in turn may cause transudation and symptoms of tissue congestion (pulmonary
and systemic).

Arginine Vasopressin (AVP)

A pituitary hormone that plays a greater role in the regulation of free water clearance and plasma
osmolality. Two types of AVP receptors have been identified. V1-receptor affects cardiac output without
affecting electrolytes or hormone levels. V2-receptor affects sodium concentration, plasma renin activity
and plasma AVP levels without affecting haemodynamics. Control of circulating AVP concentration is
abnormal in patients with heart failure, contributing to their inability to excrete free water and hence to
plasma hypoosmolarity in some patients with heart failure. The plasma AVP concentration was
significantly elevated in asymptomatic patients in the prevention arm of the “SOLVD” study and was
elevated further in patients with symptomatic heart failure.

Natriuretic Peptides
These peptides represent a favourable side of neuro-hormonal activation. They are produced by the heart
and vasculature, they appear to improve the loading conditions of the failing heart through their diuretic,
natriuretic and vasodilator properties.4

a. A-type (atrial) is secreted primarily by atrial myocardium in response to dilatation.

b. B-type (initially called brain natriuretic peptide) is manufactured and released almost exclusively
by the ventricular myocardium in response to elevations of end-diastolic pressure and volume.
c. C-Type, recently discovered, is produced and released by endothelial cells in response to shear
stress. There is some evidence that these peptides also inhibit the renin-angiotensinaldosterone
system, the endothelial pathway and AVP system.5

B-Type natriuretic peptide appears to correlate with other well-established markers of neurohormonal
activation, including sympathetic stimulation, endothelin levels, renin-angiotensinaldosterone levels.5 B-
type natriuretic peptide has the advantage that it can be measured rapidly and accurately at the point of
care. In patients with chronic heart failure, atrial concentration of ANP is unchanged, the concentrations
of BNP and CNP increase 10-fold and 2-3-fold respectively. In the “SOLVD” study, the levels of plasma
ANP were elevated even in asymptomatic patients and were further elevated in patients with symptoms.

The use of neutral endopeptidase inhibitors to inhibit the degradation of natriuretic peptides is one
approach that attempts to capitalize on their beneficial effects.

EVALUATION OF FLUID RETENTION

Physical examination is the primary step in evaluating the presence and severity of fluid retention. •
Patient’s body weight should be recorded.

 Evaluation of jugular venous distension (and its response to abdominal pressure).

 The presence and severity of organ congestion (especially the lungs and liver).
 The magnitude of peripheral oedema (in the legs, abdomen and pre-sacral area).
NB: Changes in body weight may be less reliable during long periods of followup, many patients
lose skeletal muscle mass and body fat as the disease advances, a syndrome known as “cardiac
cachexia”.

ASSESSMENT OF PRE-LOAD BY JUGULAR VENOUS EXAMINATION

a. Connord et al found it to give 42,7% accurate assessment.

b. Eisenberg et al found a 55% correlation.
c. Stevenson et al found a 75% correlation.

FLUID MANAGEMENT

1. Preload management.
2. Clinical monitoring of fluid status e.g. daily weighing, assessment of jugular venous distension,
organ congestion.
3. Monitoring technologies:
o non invasive
o invasive
4. Effects of diuretics.
5. Differentiating diuretics.

Preload
An adequate preload is necessary to maintain the cardiac output (Frank Starling).

 Preload is synonymous with enddiastolic volume or pressure.

 Increases in preload are associated with increases in cardiac output.
 Failing hearts are less responsive to changes in preload.3
 Patients self monitoring (bathroom scale) with daily recording.
 Remote telemonitoring of daily weight (the Aleregent® system).
 Future health care (Hom Med Home Health monitoring system).
 ChronicleTM implantable haemodynamic monitor.
o Implantable monitor (pacemaker size) RV lead.
o Two year battery life.
o Measures PA systolic and RV systolic pressures.
o PA diastolic and RV end-diastolic pressures.
o Maximum positive and negative RV dt/dp.
 o Heart rate, temperature activity.

Alternatives are:

 Telemetry data download/upload (office/phone/home).

 Internet based data review.

The “ESCAPE” trial primary hypothesis

For patients with severe heart failure, therapy guided by pulmonary artery catheter monitoring and
clinical assessments will lead to fewer deaths and hospital days over a 6-month period than therapy
guided by clinical assessment alone. The downside to the above are:

a. Costs of instrument.
b. Likelihood of remote sepsis.
c. Short battery life - 2 years needing regular replacement.
d. Cost of monitoring - unavailability of telemetry, satellite etc equipment.
e. Lack of intensive education/counselling programmes.

Salt and water restriction

Dietary caloric restriction is particularly necessary in overweight patients, since weight reduction lowers
demands on the heart and can provide significant relief of symptoms. Restriction of sodium intake helps
to reduce water retention with a concomitant reduction in cardiac work.

A moderate sodium restriction (1,5-3,0 gram/day) is usually necessary to achieve therapeutic, meaningful
results.

One to two litres of fluid intake (restriction) is recommended, however this is dependent on strict daily
intake and output chart, monitoring renal function closely (to prevent azotemia).

Diuretics in patients with heart failure

 Decrease end diastolic volume (PCWP).

 Decrease systemic vascular resistance (SVR).
 Acutely, may increase SVR.• Increase stroke volume.
 Increase cardiac output.
 Clinically improve exercise capacity and relieve symptoms caused by pulmonary and peripheral
congestion.

The effective dose of furosemide is usually 40 mg BID equivalent of 1 mg bumetanide BID, doses as high
as 160-240 mg/day may be necessary in heart failure. Further doses up to 1000 mg may be required in
refractory heart failure particularly with significant renal dysfunction. Preferably another diuretic with a
different nephron site of action is necessary before increasing the dose of furosemide above 120 mg
twice daily.

Thiazides are usually used in addition to loop diuretics in the treatment of resistant congestive heart
failure. It may be possible in cases of mild fluid retention, particularly in patients willing to live on
restricted fluid intake, to use thiazides as first line agents.

Combining thiazides and Loop diuretics is effective, but should be used very carefully (with great care),
this may lead to hypotension, dehydration, electrolyte imbalance (hyponatraemia/hypokalaemia) and
renal failure.
Metolazone remains effective in patients with renal impairment of at least moderate severity, offering
greater flexibility of management.

Spironolactone in the “RALES” trial showed marked reduction in death from progressive heart failure and
sudden death from cardiac causes (mean dose was 26 mg daily).

TABLE 1: SUMMARY OF MAIN TYPES OF DIURETICS

Diuretic Site of Action % Filtered Sodium Excretion

1. Potent:

 Furosemide (Lasix) Loop of Henle 15-25%

 Bumetanide (Burinex) Loop of Henle
 Torasemide (Unat) Loop of Henle

2. Moderate:

 Thiazides Cortical Diluting Segment 5-10%

 Metolazone (Zaroxolyn) Cortical Diluting Segment

3. Weak

 Spironolactone (Aldactone) Distal Tubule 1-5%

 Amiloride Distal Tubule

Adverse Effects of Diuretics

1. Hyponatraemia:
In patients with heart failure, hyponatreamia usually indicates marked stimulation of renin-
angiotensinaldosterone system (a poor prognosis sign). It is often accompanied by hypokalaemia. Great
care should be taken when starting ACE -I, and hospital supervision is indicated.

Clinically the only way of managing hyponatraemia is to institute fluid restriction (fluid restriction of 1-1,5
litres/day) if plasma sodium concentration is below 130 mmol/l.

2. Hypokalaemia:
The extent depends on the following:

 Acid base status.

 Plasma levels of aldosterone.
 Distal delivery of sodium and potassium.

Potassium deficiency increases the risk of digoxin toxicity and other antiarrhythmic agents, low dose
diuretic therapy does not cause total body potassium depletion in patients who are eating a diet rich in
potassium.

Magnesium depletion is common in diuretic treated patients, and has adverse effects in potassium
depletion. It may be impossible to correct potassium deficiency unless magnesium deficiency is corrected
first. In the light of the RALES trial addition of spironolactone to diuretics with baseline ACE I’s will help to
ameliorate this problem. Higher doses of diuretics (especially IV) need regular serum potassium level
checking (where available ECG tracings will be helpful).

Interactions
NSAID’s blunt the natriuretic effect of diuretics. NSAID’s may also cause renal dysfunction and
hyperkalaemia particularly in the elderly.

An ACE inhibitor alone may be insufficient to prevent electrolyte depletion.

CONCLUSION
Fluid retention frequently causes congestive symptoms and decompensation of heart failure. The clinical
evaluation of fluid status is often unreliable. Newer monitoring technologies may be useful in the
assessment of total body fluid status. Diuretics represent the mainstay of therapy. The goal is to achieve
normal filling pressures.

In future, trials of torasemide combined with aldactone on top of other recommended therapies may
possibly yield better outcomes and probably less side-effects.

References

1. Michael H Crawford: Current Diagnosis and Treatment in Cardiology (1st Edition 1995).
2. Milton Packer: Jay N Cohn: Consensus recommendations for the Management of Clinical Heart
Failure (The American Journal of Cardiology, 01/21/99).
3. William Abraham: How Dry is Dry? Management of Patients’ Fluid Homeostasis.
4. Randomised Aldactone Evaluation Study (RALES) (Preliminary data at AHA: Dallas 11/08-
11/1998.
5. B-Type Natriuretic Peptide: A window to the Heart. NEJM: July 18, 2002.
6. Marvin Moser: Diuretics in the Prevention and Treatment of Congestive Heart Failure:
Cardiovascular Drugs and Therapy. Volume 11; Supplement 1: May 1997.
7. HJ Dargie, JJV McMurrray and PA Poole-Wilson: Managing Heart Failure in Primary Care. 1996.
8. Eugene Braunwald: Heart Disease: a Textbook of Cardiovascular Medicine: 5th Edition 1997.