Review

High output heart failure

P.A. MEHTA
1
and S.W. DUBREY
2
From the
1
Clinical Cardiology, National Heart and Lung Institute, Imperial College, Dovehouse Street,
London SW3 6LY, UK and
2
Cardiology Department, The Hillingdon Hospital, Pield Heath Road,
Uxbridge, Middlesex, London UB8 3NN, UK
Summary
The symptoms and signs of heart failure can occur
in the setting of an increased cardiac output and has
been termed high output heart failure. An elevated
cardiac output with clinical heart failure is associated
with several diseases including chronic anaemia,
systemic arterio-venous fistulae, sepsis, hypercapnia
and hyperthyroidism. The underlying primary phys-
iological problem is of reduced systemic vascular
resistance either due to arterio-venous shunting or
peripheral vasodilatation. Both scenarios can lead to
a fall in systemic arterial blood pressure and
neurohormonal activation leading to overt clinical
heart failure. In contrast to low output heart failure,
clinical trial data in this area are lacking. The use of
conventional therapies for heart failure, such as
angiotensin converting enzyme inhibitors, angioten-
sin receptor blockers and certain b-blockers with
vasodilatory properties, is likely to further reduce
systemic vascular resistance resulting in deteriora-
tion. The condition, although uncommon, is often
associated with a potentially correctable aetiology.
In the absence of a remediable cause, therapeutic
options are very limited but include dietary restric-
tion of salt and water combined with judicious use of
diuretics. Vasodilators and b-adrenoceptor positive
inotropes are not recommended.
Introduction
The syndrome of heart failure is a global clinical
problem with at least 10 million patients across
Europe
1
and 5 million in the USA
2
living with
the condition. The condition is not confined to the
developed world. In the developing world, the
epidemiology of heart failure is largely unknown
but is likely to evolve in a similar way due to
Westernization of lifestyle and better control of
communicable disease and malnutrition.
3,4
Heart failure is usually associated with a low
cardiac output but less commonly the symptoms
and signs of heart failure can occur in the setting of a
high cardiac output. Historically this has been
termed high output heart failure.
Low output cardiac failure is well described with
a number of pharmacological therapies available
which are supported by data from many randomized
clinical trials.
514
In addition, several international
consensus guidelines are available for the diagnosis
and management of heart failure.
1,15
However, such
clinical evidence and published guidelines do not
make reference to high output heart failure.
Definition of high output cardiac
state and heart failure
A high cardiac output has been described as being
>8l/min or a cardiac index >3.9 l/min/m
2
.
16
A high
Address correspondence to P.A. Mehta, Clinical Cardiology, National Heart and Lung Institute, Imperial
College, Dovehouse Street, London SW3 6LY, UK. email: p.mehta@imperial.ac.uk
! The Author 2008. Published by Oxford University Press on behalf of the Association of Physicians.
All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Q J Med 2009; 102:235241
doi:10.1093/qjmed/hcn147 Advance Access publication 5 November 2008

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cardiac output state and associated clinical heart
failure is associated with several disease states
(Figure 1). Some authors suggest the term high
output heart failure is a misnomer as the heart is
intrinsically normal and capable of generating a
high cardiac output.
16
Others have suggested that
high output heart failure occurs only when there is
the presence of underlying heart disease.
4
It is likely
that in chronic high output states, heart failure
occurs due to eventual deterioration due to the
presence, or in most cases the development of heart
disease. A persistent high output state may be
associated with ventricular dilatation and/or hyper-
trophy, persistent tachycardia and functional valvu-
lar abnormalities, all of which may culminate in
heart failure.
Pathophysiology
The underlying primary physiological problem in
high output heart failure is of reduced systemic
vascular resistance. This occurs due to either
systemic arterio-venous shunting or peripheral
vasodilatation. Both scenarios can lead to a fall in
systemic arterial blood pressure, a feature of low
output heart failure. This can lead to sympathetic
neural activation, a compensatory rise in cardiac
output and neurohormonal activation (including the
reninangiotensinaldosterone system and vaso-
pressin). This process in turn can cause salt and
water retention and overt clinical heart failure. Thus,
salt and water retention occur both in low and high
output heart failure due to a similar neurohormonal
response to arterial hypotension.
1720
In the former it
is due to low cardiac output and in the latter due to
reduced systemic vascular resistance.
Diagnosis
Symptoms and signs
In common with low output states, patients with
high output heart failure may have a number of
symptoms including breathlessness at rest or on
exertion, exercise intolerance, fatigue and fluid
retention. The signs of typical heart failure may be
present including tachycardia, tachypnoea, raised
jugular venous pressure, pulmonary rales, pleural
effusion and peripheral oedema (Figure 2).
Direct
myocardial
toxicity
Reduced systemic vascular resistance
Vasodilatation
Chronic anaemia
Chronic hypercapnia
Thyrotoxicosis
Sepsis
Beriberi heart disease
Pregnancy
Obesity
Hepatic disease*
Carcinoid syndrome*
Systemic arterio-venous fistula
Pagets disease
Multiple myeloma
Albrights disease
Hepatic disease*
Carcinoid syndrome*
Increased
heart rate
Increased
vasoconstriction
Sympathetic activation
Arterio-venous shunting
Reduced arterial blood pressure
Reduced renal perfusion
RAAS activation
Interstitial fibrosis Salt and water retention
Ventricular remodelling
Clinical heart failure
RAAS-Renin-Angiotensin-Aldosterone-System
* Hepatic disease and carcinoid syndrome may
cause both vasodilatation and arterio-venous
shunting
Figure 1. Schematic illustrating the two common routes through which various disease states lead to a reduced systemic
vascular resistance and ultimately clinical heart failure.
236 P.A. Mehta and S.W. Dubrey

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In high output heart failure, patients are likely to
have warm rather than cold peripheries due to low
systemic vascular resistance and peripheral
vasodilatation.
Investigations
Chest radiography
A chest radiograph is essential in the investigation of
heart failure. It is useful in the assessment of
cardiomegaly, pulmonary congestion and pleural
fluid accumulation. The findings of pulmonary
disease and sepsis due to pneumonia may be
relevant in the diagnosis of high output heart failure.
Echocardiography
Cardiac ultrasound is mandatory in patients with
suspected heart failure. In high output states,
echocardiography may demonstrate a preserved left
ventricular ejection fraction (>4550%). High output
heart failure may occur despite normal left ven-
tricular systolic function. Patients may subsequently
develop compensatory left ventricular dilatation
hypertrophy. This may have eventual deleterious
consequences with worsening heart failure.
Venous blood gas
Invasive haemodynamic measurements in heart
failure patients are often not necessary and direct
measurement to confirm a high cardiac output may
not be available. A mixed venous oxygen saturation
(SvO
2
) provides an estimate of the body oxygen
consumption/delivery ratio and an approximation
of cardiac output and organ perfusion. A low SvO
2
(<65%) is associated with an inadequate cardiac
output and conversely a high SvO
2
(>75%) may
be due to a high cardiac output state.
Specific conditions associated with
high output heart failure
A wide spectrum of congenital, acquired and
iatrogenic conditions may cause a high output
state and lead to the clinical syndrome of heart
failure (Figure 1). In many cases this starts as an
adaptive physiology, such as in an athletes
heart.
2126
It is when this stimulus to change is
persistent that the adaptation can result in
reduced cardiac function. In many cases this is
the beginning of a self-perpetuating cycle of
deterioration.
Anaemia
Severe chronic anaemia can result in physiological
adjustment to maintain tissue perfusion and oxyge-
nation.
27
Anaemia can lead to peripheral vasodila-
tation, at least partly due to increased renal and
Suspected diagnosis of HF
(based on history, symptoms, signs, electrocardiography, chest radiography, natriuretic peptides)
Warm peripheries
Preserved left ventricular function *
Cardiac output >8L/min
Mixed venous oxygen saturation (SvO
2
) >70-75%
Aetiology consistent with high cardiac output state (See Figure 1)
Cool peripheries
Left ventricular systolic dysfunction*
Significant valvular disease
Cardiac output <4L/min
Mixed venous oxygen saturation (SvO
2
) <65%
Aetiology consistent with low cardiac output state (eg. myocardial infarction)
Consider high output heart failure Consider low output heart failure
*based on a number of possible investigations including echocardiography, nuclear ventriculography, cardiac catheter and cardiac
magnetic resonance imaging
Figure 2. A diagnostic strategy to distinguish low vs. high output heart failure.
High output heart failure 237

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vascular nitric oxide synthase activity
28
and low
blood viscosity.
29
Both may lead to low systemic
vascular resistance with associated neurohormonal
activation and heart failure.
27
Treatment is aimed at
correction of the underlying cause of anaemia.
Whilst cautious blood transfusion may be necessary,
rapid blood volume expansion may worsen pul-
monary oedema.
Systemic arterio-venous fistula
Systemic arterio-venous fistulae may cause high
output heart failure
30,31
due to a lowering of the
systemic vascular resistance and a compensatory
rise in cardiac output.
Acquired arterio-venous fistulae may be iatro-
genic or occasionally due to trauma. The creation of
arterio-venous fistulae in renal dialysis patients has
revealed the extent and timing of associated cardiac
adaptation. This includes increase in left ventricular
dimensions and a reduction in left ventricular
diastolic filling time. An associated increased
release of natriuretic peptides has been observed.
32
The degree of increase in cardiac output depends on
the physical size and flow magnitude of the
fistula.
31,33
Concomitant chronic anaemia will
have an additive effect. Treatment may necessitate
reversal or modification of the shunt.
Congenital arterio-venous fistulae, such as in
hepatic endotheliomas and lung and/or liver invol-
vement in hereditary haemorrhagic telengiectasia
(Osler-Weber-Rendu disease) may produce a hyper-
dynamic circulation and subsequent heart failure as
described.
3436
Arterio-venous malformations may
be in the limb with associated hypertrophy (Parkes-
Weber syndrome).
37,38
Heart failure has also been
reported in the setting of diffuse arterio-venous
malformations associated with KlippelTrenaunay
syndrome.
39
Overall, the ideal treatment is aimed at
attempting surgical excision of the causative shunt.
However, lesions may be difficult to precisely
localize or in some cases so extensive as to prevent
complete excision.
Pagets disease
Pagets disease is associated with rapid bone
formation and resorption that can lead to increased
blood flow within bone and the surrounding limb
tissue.
40
This may act or indeed cause shunting and
lower peripheral vascular resistance. Significant
bony involvement (usually defined as >15%) may
then lead to heart failure.
41,42
Both multiple
myeloma
43,44
and fibrous dysplasia (Albrights dis-
ease), by a similar mechanism have been associated
with arterio-venous shunting and high output heart
failure. Again, concomitant anaemia is likely to
exacerbate this process.
Chronic hypercapnia
Chronic hypercapnia is associated with vasodilata-
tion and can potentially lead to systemic hypoten-
sion and subsequent adverse neurohormonal
response.
45,46
Hypercapnia is commonly seen in
clinical practice due to chronic obstructive pulmon-
ary disease and cor pulmonale. These conditions
can lead to fluid retention in the setting of normal/
increased cardiac output.
Hyperthyroidism
Thyrotoxicosis is associated with a hyperdynamic
circulation. There can be associated tachycardia,
left ventricular dilatation and increased cardiac
output.
4750
The development of heart failure may
be predominantly due to tachycardia-mediated
cardiomyopathy as observed with many other
causes of tachycardia including atrial fibril-
lation.
51,52
Sepsis
Sepsis and associated endotoxaemia is a complex
and multifactorial process. Severe septicaemia is
associated with systemic vasodilatation and an
increased cardiac output.
53,54
A number of vasoac-
tive cytokines including tumour necrosis factor-a,
interleukins-2, -6, -8 and -15 and inducible nitric
oxide synthase have been implicated in this
process.
5557
The end-result is sometimes significant
systemic vasodilatation culminating in arterial
hypotension and high output failure.
Beriberi heart disease
This condition is due to severe long-term (>3
months) deficiency of the B vitamin thiamine and
is more common in areas of dietary deficiency with
high carbohydrate intake (such as the Far East). In
the developed world it is most frequently observed
in chronic alcoholics due to poor dietary intake of
thiamine, impaired thiamine absorption, metabo-
lism and storage. Thiamine deficiency is also
associated with malabsorption conditions, dialysis
and other causes of chronic protein-calorie under-
nutrition. The latter should be suspected in isolated
elderly patients. Beriberi heart disease is a cause of
heart failure with associated elevated cardiac
output, oedema, fatigue and general malaise (wet
beriberi). High output heart failure is possibly due to
arteriolar and cutaneous vasodilatation leading to a
reduced systemic vascular resistance.
58,59
238 P.A. Mehta and S.W. Dubrey

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Obesity
Obesity produces an increase in overall blood
volume and cardiac output. This is due to the
raised metabolic activity of excessive adipose tissue,
which leads to compensatory cardiac changes
including left ventricular dilatation and eccentric
hypertrophy. These adaptive modifications can
eventually lead to both systolic and diastolic
abnormalities culminating in heart failure or obesity
cardiomyopathy.
6065
Obesity cardiomyopathy is
likely to become increasingly prevalent over time
due to a rising global epidemic of obesity.
Other causes
There are many other causes of high output heart
failure including pregnancy, hepatic disease and
carcinoid syndrome. All are related, via a common
mechanism, to vasodilatation and a fall in blood
pressure.
Treatment
Although the final pathogenesis of salt and water
retention is similar in low and high output states,
treatment options differ. In low output heart failure,
with associated normal or high systemic vascular
resistance, circulating vasoconstrictors predominate
and are counteracted by neurohormonal antagonists
(angiotensin converting enzyme inhibitors, angio-
tensin receptor blockers, aldosterone antagonists
and b-blockers). Extensive clinical trial data support
the use of such therapies with improvement in
mortality and morbidity.
514
The evidence base for the management of high
output failure is scarce and generally based on case
reports. Clinical trial data in this area are lacking.
The use of established vasodilator therapies, such as
angiotensin converting enzyme inhibitors, angioten-
sin receptor blockers and some newer b-blockers
with vasodilatory properties (e.g. carvedilol, nebi-
volol), in patients with low systemic vascular
resistance in high output heart failure is likely to
lead to further deterioration and is not recom-
mended. In addition the use of b-adrenoceptor
positive inotropes is not advisable.
Treatment should be targeted at correcting the
cause of low systemic vascular resistance. In
addition dietary restriction of salt and water and
judicious use of diuretics is advised. Although
treatment options are limited for high output heart
failure, there are some existing supportive therapies.
A number of intravenous vasoconstrictor adren-
ergic drugs are available including noradrenaline,
ephedrine, metaraminol and phenylephrine.
These treatments increase systemic vascular resis-
tance by acting on a-adrenergic receptors to
constrict peripheral blood vessels. Such therapies
may be useful short-term adjuncts in high output
heart failure whilst treatment of the underlying
aetiology is ongoing. Long-term treatment may be
associated with both reduced vital organ perfusion
and tachycardia due to b-adrenergic receptor
activation (e.g. ephedrine) and is not recommended.
Respiratory intervention with high ventilatory peak
end-expiratory pressure for resistant pulmonary
oedema may also be useful.
Conclusion
Many conditions are associated with high cardiac
output physiology. When this becomes chronic the
adaptive cardiac changes can fail, resulting in
cardiovascular decompensation. Overt high output
heart failure, although uncommon, is often asso-
ciated with a potentially correctable aetiology.
There is a notable lack of clinical trial data for this
poorly understood condition. In the absence of a
remediable cause, therapeutic options are limited.
Moreover, many accepted therapies for low output
heart failure are in fact contra-indicated.
Conflict of interest: None declared.
References
1. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F,
Komajda M, et al. Guidelines for the diagnosis and treatment
of chronic heart failure: executive summary (update 2005):
The Task Force for the Diagnosis and Treatment of Chronic
Heart Failure of the European Society of Cardiology. Eur
Heart J 2005; 26:111540.
2. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS,
Ganiats TG, et al. ACC/AHA 2005 Guideline Update for the
Diagnosis and Management of Chronic Heart Failure in the
Adult-Summary Article A Report of the American College of
Cardiology/American Heart Association Task Force on
Practice Guidelines (Writing Committee to Update the
2001 Guidelines for the Evaluation and Management of
Heart Failure). J Am Coll Cardiol 2005; 46:111643.
3. Mendez GF, Cowie MR. The epidemiological features of
heart failure in developing countries: a review of the
literature. Int J Cardiol 2001; 80:2139.
4. Braunwald E, Grossman W. Clinical aspects of heart failure.
In: Braunwald E, ed. Heart Disease: A Textbook of
Cardiovascular Medicine, 4th edn. Philadelphia: Saunders,
1992:444.
5. The CONSENSUS Trial Study Group.Effects of enalapril on
mortality in severe congestive heart failure. Results of the
Cooperative North Scandinavian Enalapril Survival Study
(CONSENSUS). N Engl J Med 1987; 316:142935.
6. Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.
Effect of ramipril on mortality and morbidity of survivors of
High output heart failure 239

b
y

g
u
e
s
t

o
n

J
u
l
y

1
7
,

2
0
1
4
h
t
t
p
:
/
/
q
j
m
e
d
.
o
x
f
o
r
d
j
o
u
r
n
a
l
s
.
o
r
g
/
D
o
w
n
l
o
a
d
e
d

f
r
o
m

acute myocardial infarction with clinical evidence of heart
failure. Lancet 1993; 342:8218.
7. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr,
Cuddy TE, et al. Effect of captopril on mortality and morbidity
in patients with left ventricular dysfunction after myocardial
infarction. Results of the survival and ventricular enlargement
trial. The SAVE Investigators. N Engl J Med 1992;
327:66977.
8. TRACE Study Group. A clinical trial of angiotensin convert-
ing enzyme inhibitor trandolapril in patients with left
ventricular dysfunction after myocardial infarction. The
Trandolapril Cardiac Evaluation (TRACE) Study. N Engl J
Med 1995; 333:16706.
9. MERIT-HF Study Group. Effect of metoprolol CR/XL in
chronic heart failure: metoprolol CR/XL randomised
Intervention Trial in Congestive Heart Failure (MERIT-HF).
Lancet 1999; 353:20017.
10. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B,
et al. Eplerenone, a selective aldosterone blocker, in patients
with left ventricular dysfunction after myocardial infarction.
N Engl J Med 2003; 348:130921.
11. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A,
et al. The effect of spironolactone on morbidity and mortality
in patients with severe heart failure. Randomized Aldactone
Evaluation Study Investigators. N Engl J Med 1999;
341:70917.
12. The SOLVD Investigators. Effect of enalapril on survival
in patients with reduced left ventricular ejection fractions
and congestive heart failure. N Engl J Med 1991;
325:293302.
13. CIBIS-II Investigators and Committees. The Cardiac
Insufficiency Bisoprolol Study II (CIBIS-II): a randomised
trial. Lancet 1999; 353:913.
14. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB,
Gilbert EM, et al. The effect of carvedilol on morbidity and
mortality in patients with chronic heart failure. U.S.
Carvedilol Heart Failure Study Group. N Engl J Med 1996;
334:134955.
15. National Institute for Clinical Excellence. Chronic heart
failure. Management of chronic heart failure in adults in
primary and secondary care. National Institute for Clinical
Excellence 2003. [http://www.nice.org.uk/pdf/
CG5NICEguidelines.pdf] (May 2008, date last accessed).
16. Anand IS, Florea VG. High output cardiac failure. Curr Treat
Options Cardiovasc Med 2001; 3:1519.
17. Poole-Wilson PA. Chronic heart failure: cause, pathophy-
siology, prognosis, clinical manifestations, investigations. In:
Julian DG, Camm AJ, Fox KF, Hall RJC, Poole-Wilson PA,
eds. Diseases of the Heart, 1st edn. Bailliere-Tindall,
1989:2436.
18. Riegger GA, Liebau G, Bauer E, Kochsiek K. Vasopressin and
renin in high output heart failure of rats: hemodynamic
effects of elevated plasma hormone levels. J Cardiovasc
Pharmacol 1985; 7:15.
19. Cohn JN, Levine TB, Francis GS, Goldsmith S. Neurohumoral
control mechanisms in congestive heart failure. Am Heart J
1981; 102(3 Pt 2):50914.
20. Schrier RW. Pathogenesis of sodium and water retention in
high-output and low-output cardiac failure, nephrotic
syndrome, cirrhosis, and pregnancy (2). N Engl J Med
1988; 319:112734.
21. Pelliccia A, Maron BJ, Culasso F, Spataro A, Caselli G.
Athletes heart in women. Echocardiographic characteriza-
tion of highly trained elite female athletes. JAMA 1996;
276:21115.
22. Pelliccia A, Culasso F, Di Paolo FM, Maron BJ. Physiologic
left ventricular cavity dilatation in elite athletes. Ann Intern
Med 1999; 130:2331.
23. Makan J, Sharma S, Firoozi S, Whyte G, Jackson PG,
McKenna WJ. Physiological upper limits of ventricular cavity
size in highly trained adolescent athletes. Heart 2005;
91:4959.
24. Kervancioglu P, Hatipoglu ES. Echocardiographic eval-
uation of left ventricular morphology and function in
young male football players and runners. Cardiol J 2007;
14:3743.
25. Tumuklu MM, Ildizli M, Ceyhan K, Cinar CS. Alterations in
left ventricular structure and diastolic function in professional
football players: assessment by tissue Doppler imaging and
left ventricular flow propagation velocity. Echocardiography
2007; 24:1408.
26. Tumuklu MM, Etikan I, Cinar CS. Left ventricular function in
professional football players evaluated by tissue Doppler
imaging and strain imaging. Int J Cardiovasc Imaging 2008;
24:2535.
27. Anand IS, Chandrashekhar Y, Ferrari R, Poole-Wilson PA,
Harris PC. Pathogenesis of oedema in chronic severe
anaemia: studies of body water and sodium, renal function,
haemodynamic variables, and plasma hormones. Br Heart J
1993; 70:35762.
28. Ni Z, Morcos S, Vaziri ND. Up-regulation of renal and
vascular nitric oxide synthase in iron-deficiency anemia.
Kidney Int 1997; 52:195201.
29. Fowler NO, Holmes JC. Blood viscosity and cardiac output
in acute experimental anemia. J Appl Physiol 1975;
39:4536.
30. Bergrem H, Flatmark A, Simonsen S. Dialysis fistulas and
cardiac failure. Acta Med Scand 1978; 204:1913.
31. Anderson CB, Codd JR, Graff RA, Groce MA, Harter HR,
Newton WT. Cardiac failure and upper extremity arterio-
venous dialysis fistulas. Case reports and a review of the
literature. Arch Intern Med 1976; 136:2927.
32. Iwashima Y, Horio T, Takami Y, Inenaga T, Nishikimi T,
Takishita S, et al. Effects of the creation of arteriovenous
fistula for hemodialysis on cardiac function and natriuretic
peptide levels in CRF. Am J Kidney Dis 2002; 40:97482.
33. Ponsin JC, Levy B, Martineaud JP. Cardiac effects of the flow
in the arteriovenous fistula. Study in 66 chronic hemodialysis
patients. Presse Med 1983; 12:21721.
34. Montejo BM, Perez M, De AJ, De la HC, Merino J, Aguirre C.
High out-put congestive heart failure as first manifestation
of Osler-Weber-Rendu disease. Angiology 1984; 35:56876.
35. Brohee D, Franken P, Fievez M, Baudoux M, Henuzet C,
Brasseur P, et al. High-output right ventricular failure
secondary to hepatic arteriovenous microfistulae. Selective
arterial embolization treatment. Arch Intern Med 1984;
144:12824.
36. Bourgeois N, Delcour C, Deviere J, Francois A, Lambert M,
Cremer M, et al. Osler-Weber-Rendu disease associated with
hepatic involvement and high output heart failure. J Clin
Gastroenterol 1990; 12:2368.
240 P.A. Mehta and S.W. Dubrey

b
y

g
u
e
s
t

o
n

J
u
l
y

1
7
,

2
0
1
4
h
t
t
p
:
/
/
q
j
m
e
d
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o
x
f
o
r
d
j
o
u
r
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a
l
s
.
o
r
g
/
D
o
w
n
l
o
a
d
e
d

f
r
o
m

37. Robertson DJ. Congenital arteriovenous fistulae of the
extremities. Ann R Coll Surg Engl 1956; 18:7398.
38. Weber F.P. Angioma formation in connection with hyper-
trophy of limbs and hemihypertrophy. Brit J Derm 1907;
19:2315.
39. Gwinn JL, Lee FA. Congestive heart failure secondary to
peripheral arteriovenous malformation. Klippel-Trenaunay
syndrome. Am J Dis Child 1977; 131:8990.
40. Heistad DD, Abboud FM, Schmid PG, Mark AL, Wilson WR.
Regulation of blood flow in Pagets disease of bone. J Clin
Invest 1975; 55:6974.
41. Henley JW, Croxson RS, Ibbertson HK. The cardiovascular
system in Pagets disease of bone and the response to therapy
with calcitonin and diphosphonate. Aust N Z J Med 1979;
9:3907.
42. Arnalich F, Plaza I, Sobrino JA, Oliver J, Barbado J, Pena JM,
et al. Cardiac size and function in Pagets disease of bone. Int
J Cardiol 1984; 5:491505.
43. McBride W, Jackman JD Jr, Gammon RS, Willerson JT. High-
output cardiac failure in patients with multiple myeloma.
N Engl J Med 1988; 319:16513.
44. Inanir S, Haznedar R, Atavci S, Unlu M. Arteriovenous
shunting in patients with multiple myeloma and high-output
failure. J Nucl Med 1998; 39:13.
45. Fowler NO, Wescott RN, Scott RC, Hess E. The cardiac
output in chronic cor pulmonale. Circulation 1952;
6:88893.
46. Anand IS, Chandrashekhar Y, Ferrari R, Sarma R, Guleria R,
Jindal SK, et al. Pathogenesis of congestive state in chronic
obstructive pulmonary disease. Studies of body water and
sodium, renal function, hemodynamics, and plasma hor-
mones during edema and after recovery. Circulation 1992;
86:1221.
47. Lewis BS, Ehrenfeld EN, Lewis N, Gotsman MS.
Echocardiographic LV function in thyrotoxicosis. Am Heart
J 1979; 97:4608.
48. Wilson BE, Newmark SR. Thyrotoxicosis-induced congestive
heart failure in an urban hospital. Am J Med Sci 1994;
308:3448.
49. Froeschl M, Haddad H, Commons AS, Veinot JP.
Thyrotoxicosis-an uncommon cause of heart failure.
Cardiovasc Pathol 2005; 14:247.
50. Blasco PF, Perez MR, Roman GF, Lopez de Letona JM,
Villares P, Jimenez AI. High output heart failure and
pulmonary acute edema as presentation of thyrotoxicosis
secondary to toxic multinodular goiter. Rev Clin Esp 2004;
204:6089.
51. Watanabe H, Okamura K, Chinushi M, Furushima H,
Tanabe Y, Kodama M, et al. Clinical characteristics,
treatment, and outcome of tachycardia induced cardiomyo-
pathy. Int Heart J 2008; 49:3947.
52. Peake ST, Mehta PA, Dubrey SW. Atrial fibrillation-related
cardiomyopathy: a case report. J Med Case Rep 2007; 1:111.
53. Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl
J Med 1993; 328:14717.
54. Rotheram EB Jr. High output congestive heart failure in septic
shock. Chest 1989; 95:13678.
55. Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for
pathogenesis of the disease process. Chest 1997;
112:23543.
56. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology,
pathophysiology, and pharmacology. Pharmacol Rev 1991;
43:10942.
57. Rees DD, Monkhouse JE, Cambridge D, Moncada S. Nitric
oxide and the haemodynamic profile of endotoxin shock in
the conscious mouse. Br J Pharmacol 1998; 124:5406.
58. Akbarian M, Yankopoulos NA, Abelmann WH.
Hemodynamic studies in beriberi heart disease. Am J Med
1966; 41:197212.
59. Ayzenberg O, Silber MH, Bortz D. Beriberi heart disease.
A case report describing the haemodynamic features. S Afr
Med J 1985; 68:2635.
60. Alpert MA. Obesity cardiomyopathy: pathophysiology and
evolution of the clinical syndrome. Am J Med Sci 2001;
321:22536.
61. Alpert MA, Hashimi MW. Obesity and the heart. Am J Med
Sci 1993; 306:11723.
62. Galinier M, Pathak A, Roncalli J, Massabuau P. Obesity and
cardiac failure. Arch Mal Coeur Vaiss 2005; 98:3945.
63. Barzizza F. Obesity and the heart. Minerva Gastroenterol
Dietol 2001; 47:22934.
64. Contaldo F, Pasanisi F, Finelli C, de Simone G. Obesity, heart
failure and sudden death. Nutr Metab Cardiovasc Dis 2002;
12:1907.
65. Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ,
Larson MG, et al. Obesity and the risk of heart failure. N Engl
J Med 2002; 347:30513.
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