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[10] Schiele F, Meneveau N, Vuillemenot A et al. Impact of IVUS
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European Heart Journal (2000) 21, 94–96
Article No. euhj.1999.1669, available online at http://www.idealibrary.com on
Diagnosing primary diastolic heart failure
With the increasing refinement of methods to uncover
early phases of cardiac failure, we have, over the past
two decades, witnessed the emergence of diastolic
dysfunction and diastolic failure of the heart as
separate, widely recognized clinical entities. Whereas
the majority of the conditions related to diastolic
dysfunction and failure are the mere consequence of
systolic cardiac failure, there also exists a distinct
primary form of diastolic failure. Primary diastolic
failure has been commonly defined as a condition
with classic findings of congestive heart failure
with normal ventricular systolic function, but with
predominantly diastolic dysfunction. It has been
observed in a large variety of clinical conditions and
was believed to occur more commonly — at least in
the elderly population — than previously thought,
accounting for about 30% to 40% of all patients with
congestive heart failure.
In an excellent review, Vasan et al.[1] surveyed 31
studies on diastolic failure published in the period
January 1970–March 1995. From their critical analysis, the authors were astonished to find that the
prevalence of primary diastolic heart failure, i.e.
patients with congestive heart failure and normal
ventricular systolic performance, varied widely from
13% to 74%. Despite the many possible causes, interpretations and warnings suggested by these authors,
it is surprising that their conclusions were not taken
more seriously. Similar criticisms were recently raised
by Caruana et al.[2]. In a Letter to the Editor in
the European Heart Journal (20/5), Caruana et al.
responded to a report entitled ‘How to diagnose
diastolic heart failure’ by the European Study Group
on Diastolic Heart Failure[3]. In the Working Group’s
Report, it was stated that a diagnosis of primary
diastolic heart failure requires three obligatory conditions to be satisfied simultaneously: (1) presence of
signs or symptoms of congestive heart failure; (2)
presence of normal or only mildly abnormal left
ventricular systolic function; (3) evidence of abnormal left ventricular relaxation, filling, diastolic distensibility or diastolic stiffness. Using echocardiographic
examination in patients with dyspnoea but no apparent left ventricular systolic dysfunction, Caruana
et al. observed a prevalence of primary diastolic
dysfunction of 3–5% when using an E/A ratio in
association with deceleration time, but of 27% if
isovolumic ventricular relaxation time was used.
There was poor overlap between subjects found to be
‘abnormal’ by each of the two different criteria, with
only 2–3% when both indices were combined. From
this, the authors concluded (i) that different measures
of diastolic dysfunction give different prevalences
of primary diastolic failure, and (ii) that there is
no simple echocardiographic means of reliably
diagnosing diastolic dysfunction.
As previously stated by Vasan et al.[1], only two
reasons could possibly account for this somewhat
absurd wide variation in clinical prevalence of primary diastolic heart failure. Either there is no agreement of what should be considered as near-normal
systolic function and how it should be measured, or
there is no clear, generally agreed definition of diastolic dysfunction or failure. Moreover, as many conditions may clinically resemble primary diastolic
failure, one should first exclude all non-cardiac causes
2000 The European Society of Cardiology
Editorials
of dyspnoea or pulmonary congestion, such as for
example, pulmonary diseases, obesity, or pregnancy,
as well as conditions of circulatory overload, such as
for example in renal insufficiency, iatrogenic fluid
overload, or valvular regurgitant lesions.
Normal systolic function?
In most studies on primary diastolic cardiac failure[1],
normal systolic function is derived from the measurement of a left ventricular ejection fraction above
0·35–0·45. The wide and uncritical application of
ejection fraction, or any related measurement as e.g.
fractional shortening, in clinical cardiology as an
index of systolic function, follows from the worldwide
availability and easy accessibility of powerful noninvasive techniques such as echo-Doppler and radionuclide imaging. Ejection fraction is generally
recognized as an excellent and a most convenient
screening test to distinguish bad from good mean
overall pump performance. It is, however, a poor and
non-specific measure of ventricular systolic function.
Ejection fraction does not provide direct information
on intrinsic muscle performance or myocardial contractility, on ventricular contraction and ejection
properties and patterns, on stroke work, stroke power,
on non-uniformity, and it does not allow ventricular
contractile dysfunction to be distinguished from
changes in loading conditions. Moreover, as ejection
fraction reflects mean overall pump function, it reflects
combined steady-state systolic and diastolic properties. But even in the presence of mild systolic and/or
diastolic dysfunction, the mean overall pump performance, and hence ejection fraction, may still be normal
as a result of the many compensatory mechanisms.
Abnormal diastolic function?
The concepts of diastolic dysfunction and failure are
still not well understood by many clinicians. This
is another reason why the diagnosis and clinical
prevalence continue to cause major controversies.
One reason for confusion is use of the connotations
‘diastolic dysfunction’ and ‘diastolic failure’ interchangeably[4]. Diastolic dysfunction should be viewed
as a condition with increased resistance to filling of
the left ventricle, leading to an inappropriate rise
in the diastolic (i.e. end-portion) pressure–volume
relationship and causing symptoms of pulmonary
congestion during exercise. By contrast, diastolic
failure should indicate that all of the above occurs
when the patient is at rest.
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More worrisome, however, is the fact that with the
wide application of the above powerful non-invasive
techniques, clinical cardiologists believe that a quick
and correct diagnosis of diastolic cardiac dysfunction
and diastolic failure is now feasible. The often uncritical application of these techniques, as the sole basis
for diagnosis and therapy, without sufficient knowledge of the underlying pathophysiological concepts of
cardiac muscle-pump performance, has indeed led to
the many diagnostic misinterpretations of systolicversus-diastolic dysfunction and failure, and hence to
the growing controversies in the area of ‘diastology’.
Let me explain.
Ventricular relaxation in the intact heart is characterized by the fact that its timing, with respect to the
onset of systole, may, in various conditions, undergo
substantial shifts which are unrelated to changes in
heart rate[4]. These shifts in ventricular relaxation
timing result in significant changes in the overall
duration of the ventricular contraction–relaxation
cycle, often amounting to about 30% or more of the
time between the onset of systole until early rapid
filling. As a result, ventricular systolic function can be
quickly adjusted to pressure and volume loading[5,6],
to neurohumoral factors[7], and to endothelial or
cytokine[8] modulation through shifts in the timing of
onset of ventricular relaxation, often with little or no
changes in ventricular contraction or ejection parameters. In 1997, Paulus and his colleagues[8] introduced an elegant, invasive novel index of ventricular
systolic function which takes into account these time
shifts of the ventricular relaxation phase. Similarly,
Tei et al.[9] suggested a non-invasive Doppler-derived
index of systolic function, to measure the combined
contraction and relaxation time intervals of the left
ventricle.
In the adjustments of systolic function, through
alterations in the timing of ventricular relaxation,
relaxation rate is, in general, unpredictable and of no
value in diagnosing ‘abnormal’ ventricular relaxation.
In a literature survey of the past 20 years, we found
that variations in systolic ‘duration’, such as for
example during pressure or volume loading, were
consistent despite the auxotonic conditions and
despite often important non-uniformities during
ventricular relaxation[4]. By contrast, and regardless
of these changes in systolic duration, ventricular
relaxation ‘rate’ either increased, or decreased, or
remained unaltered. Measurements of relaxation
‘rates’ are, therefore, of doubtful diagnostic value. A
measurement of ventricular relaxation rate commonly used by echocardiographers is the isovolumic
ventricular relaxation time. Isovolumic ventricular
relaxation time as a measure of relaxation rate is,
however, similar to all other relaxation ‘rate’
Eur Heart J, Vol. 21, issue 2, January 2000
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Editorials
measurements, an unreliable index of performance if
not first normalized or corrected, with often substantial shifts in the timing of ventricular relaxation.
Evaluation of ventricular relaxation should, therefore, include timing of this phase of the cardiac cycle
with respect to the onset of systole, in addition to
rate, extent and pattern[4]. Abnormalities of these
various aspects of ventricular relaxation, for example
inappropriate shifts in timing, rate, extent or pattern,
are, in view of the above, a first sign of systolic
dysfunction or failure. In the early phases of various
cardiac diseases, such as for example in ischaemic or
hypertrophic cardiomyopathy, ventricular relaxation
abnormalities may be detectable long before contraction and ejection abnormalities, and are, therefore,
sensitive indicators of systolic dysfunction. Of course,
in specific circumstances impairment of these late
systolic events during ventricular relaxation may lead
to an inappropriate rise in the end-diastolic pressure–
volume ratio with clinical symptoms of pulmonary
congestion. This would be strongly suggestive for
the presence of secondary diastolic dysfunction and
failure due to combined systolic–diastolic failure. It
can be anticipated that the use of an ejection fraction
above 0·40–0·45, as the sole index of normal systolic
function, will obviously overlook these early, subtle
aspects of impaired ventricular systolic function.
From a physiological point of view, all the above
in-vivo features of ventricular relaxation can be easily
understood. The underlying physiological and pathophysiological concepts have been reviewed extensively[4,10]. Both on experimental and conceptual
grounds, ventricular relaxation should be considered
as an integral part of ventricular systole, i.e. of one
continuous contraction–relaxation cycle of the heart.
Identifying measurements or derived indices related
to ventricular relaxation with diastole is, therefore,
conceptually incorrect. Ironically, although most
clinicians would agree that shifts in the ‘timing’ of
ventricular relaxation are an integral part of systolic
adjustments, many[9] continue to consider the rate of
that same phase of the cardiac cycle as diastolic.
In conclusion, from all the above it must be clear
that echo-Doppler has been clearly overrated with
respect to its potential value in evaluating diastolic
function, in particular by promoting measurements
such as isovolumic ventricular relaxation time or
Eur Heart J, Vol. 21, issue 2, January 2000
other ‘rate’ measurements of ventricular relaxation,
as indices of diastolic function. As a consequence, this
non-invasive technique has contributed significantly
to the excessive diagnosis of primary diastolic dysfunction and failure. Genuine abnormal ventricular
relaxation, as described above and after normalization for shifts in relaxation timing, should be interpreted as an early sign of systolic dysfunction. With
these recommendations in mind and with the strict
application of the three obligatory, diagnostic criteria
proposed by the European Study Group on Diastolic
Heart Failure — except for the inclusion of abnormalities of left ventricular relaxation as part of the
third criterium — it can be anticipated that the prevalence of genuine primary diastolic heart failure, i.e. in
the absence of systolic contraction or relaxation
abnormalities, is far less common than previously
thought.
D. L. BRUTSAERT
University of Antwerp,
Antwerp, Belgium
References
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and prognosis of diastolic heart failure: an epidemiologic
perspective. J Am Coll Cardiol 1995; 26: 1565–74.
[2] Caruana L, Davie AP, Petrie M, McMurray J. Diagnosing
heart failure. Letters to the Editor. Eur Heart J 1999; 20: 393.
[3] European Study Group on Diastolic Heart Failure. How to
diagnose diastolic heart failure. Eur Heart J 1998; 19: 990–
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[4] Brutsaert DL, Sys SU. Diastolic Dysfunction in Heart
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