Diastolic dysfunction

Diastolic dysfunction (DD) is very common. In 2042 adults over 45, randomly selected from the general population in Minnesota (by the Mayo Clinic), 21% had mild and 7% had at least moderate diastolic dysfunction! In contrast, only six percent of all people examined had some systolic dysfunction. Of the thirteen people with severe DD, only six had a history of congestive heart failure. [JAMA 2003 Jan 8; 289:194-202] DD is particularly common in the elderly [Cardiovasc Res 2000 Mar;45(4):813-25].

Diastolic dysfunction appears to cause a lot of morbidity from heart failure. Up to 40% of heart failure patients have DD [Eur J Heart Fail 2002 Aug;4(4):419-30]. In addition, DD appears early on post acute myocardial infarction, and may predict poor outcomes. In one study (Am Heart J 137(5):910-918, 1999), E deceleration time was predictive of subsequent heart failure or death, and in hospital heart failure correlated well with diastolic dysfunction; those who had normal filling were free of heart failure.

Some would argue that in those who have signs and symptoms of heart failure, but have preserved LV systolic function, diastolic function will be found. Zile et al [Circulation 2001 Aug 14;104(7):779-82] examined 63 such patients with clinical heart failure and preserved systolic function, all of whom were found to have at least one feature of DD (abnormal time constant of LV relaxation, E/A ratio, or E wave deceleration).

What is DD?

Note the two (poorly distinguished) components to DD:

  1. Poor relaxation (impaired lusiotrophy )
  2. Decreased compliance

The literature is very confusing (and perhaps confused) in this regard - few seem to distinguish adequately between these components!

Diagnosis

We commonly diagnose DD based on the presence of:

  • Clinical features of heart failure, particularly left heart failure;
  • A normal ejection fraction (over 50%);
  • Increased diastolic filling pressure.

The first two are relatively easily identified, but what about the third? Invasive intervention seems pretty aggressive, so other measures have been proposed as an indicator of diastolic pressures. People have looked at:

  1. Isovolumic relaxation time (IVRT, IRT) - this (the time from aortic valve closure to mitral valve opening) is measured by simultaneous Doppler and M-mode echo, or better still by simultaneous phonocardiogram and transmitral Doppler (Roelandi). If it's prolonged, it indicates poor myocardial relaxation. A normal IRT is about 70±12 ms, perhaps about 10ms longer in those over forty. With abnormal relaxation, the value is usually in excess of 110ms, with restrictive filling, under 60.

  2. transmitral inflow (E/A; E wave deceleration) The E wave occurs related to LV `suction' and LA pressure - the E wave acceleration will be higher with high LA pressure, and lowered with impaired LV relaxation. Deceleration of inflow of the E wave is measured by deceleration time (DT), which shortens with decreasing LV compliance. DT is rather complex, as higher LA pressures shorten it. A normal DT is about 200±32ms; values over 240ms indicate impaired relaxation, and under 150ms suggest restriction. There are a lot of problems with relying on E/A ratios, as the effects of impaired relaxation and restriction counterbalance one another, resulting in 'pseudonormalisation'.
  3. pulmonary venous inflow (atrial flow reversal) Pulmonary vein Doppler is easily imaged using TOE, but may even be performed on TTE using a foreshortened apical cross-section (RUPV). The normal pattern is to see a systolic (S) wave, a diastolic (D) wave, with perhaps some retrograde flow during atrial contraction. The last wave is sometimes called the A R wave - it normally has an amplitude of under 25cm/s, and a shorter duration than the transmitral A wave. Velocity and duration of A R increase with worsening diastolic dysfunction.

E:A ratios

Normally, early filling exceeds the atrial component of filling, and so the mitral inflow velocity profile shows a bigger E than A wave. With impaired relaxation, the E component will be reduced, resulting in a lower E:A ratio. Conversely, with a restrictive pattern, the E component is said to be increased , resulting in an abnormally high E:A.

The whole assessment of diastolic dysfunction seems bedevilled by classifications that assume a progression from:

  1. mild dysfunction (E/A under 1, IVRT over 100ms, normal E wave deceleration, atrial reversal of pulmonary venous inflow < 0.35 m/s), to
  2. mild...moderate diastolic dysfunction (similar E/A and IVRT, but atrial reversal over 0.35, and over 20ms greater than mitral A wave duration)
  3. moderate disease ("pseudonormalisation" --- apparently normal E/A, atrial reversal over 0.35)
  4. severe dysfunction ("restrictive" --- large E and small A, short E deceleration of under 120ms, short IVRT, reduced pulmonary systolic wave)

Now, the above progression may be common, but is by no means inevitable. In some conditions, either impaired relaxation (e.g. hypertrophic cardiomyopathy) or restriction (restrictive cardiomyopathies, for example) may prevail. With impaired relaxation, early filling is impaired; conversely, with a restrictive pattern, the E/A ratio increases , as early filling is favoured! If both are present, then we have the dreaded "pseudonormalisation".

Note that, with pseudonormalisation, a method of bringing out abnormality is to alter loading patterns, with Valsalva, glyceryl trinitrate, or even nitroprusside.

Tissue Doppler imaging (TDI, DTI)

TDI of the mitral apparatus is said to be less load-dependent than mitral inflow parameters. An E' and A' wave are seen, corresponding to the E and A waves on mitral inflow. Apart from providing an assessment of LV dP/dT, TDI has been proposed as a way of determining whether a 'normal' mitral inflow is actually 'pseudonormal'. With a pseudonormal pattern, restriction and impaired relaxation are balanced, and the E/A ratio looks normal because of the high LA pressure. E' will velocity will still be abnormal as it's relatively load independent.

TDI may even be of value in the presence of atrial fibrillation, where there's no A wave. Diastolic dysfunction may well be present with a DT under 150ms, E/E' ratio over 15 using TDI, and Pv under 40cm/s on colour M-mode, provided one looks at cycles corresponding to a rate of 60--80/min.

Colour M-mode transmitral flow

This is said to provide a rapid screening tool for diastolic inflow abnormality. An M-mode cursor is placed parallel to the mitral inflow, and adjusted to maximise the length of the column of colour flow into the LV. During early filling, the "slope along a distinct isovelocity line" is measured. The normal value is under 40cm/s. Those who find terms such as "isovelocity lines" unintelligible should take comfort from the likelihood that even these fancy techniques may not be incredibly reliable. (See the note on strain rate imaging below).

Invasive assessment

If one looks at the time constant of the exponential pressure decay during isovolumic relaxation, this should be an indicator of lusiotropy. Passive elastic properties should be evaluable from the slope of the diastolic pressure volume curve, and "stress-strain relationship"

Strain rate imaging

A new buzz-word. A wave of myocardial stretch propagates from the base of the heart to its apex, and this wave is slowed with impaired myocardial relaxation. Unfortunately, the propagation of flow doesn't correlate awfully well with propagation of strain rate. The flow propagation depends not only on relaxation, but also on flow velocity. (See [Cardiovasc Ultrasound. 2003; 1 (1): 3. Støylen A, Skjelvan G,Skjaerpe T]).

Managment

It should be clear from the above that accurate diagnosis of DD is non-trivial. On a practical note, if the size of the left atrium is normal, then diastolic dysfunction is said to be extremely unlikely.

If someone has preserved systolic function and clinical heart failure, it is reasonable to assume the presence of diastolic dysfunction. Such patients may respond to 'classical' therapy of heart failure such as diuretics, but such intervention may impair cardiac output more than would be expected with LV systolic dysfunction. More reasonable is to administer agents that will treat the diastolic dysfunction! The following agents may be of value:

  • calcium channel blockers (but beware of some with associated ischaemic heart disease)
  • beta blockers
  • ACE inhibitors and AT-II receptor antagonists.

Where there are other co-morbidities (such as severe respiratory disease) that cloud the clinical picture, diagnosis of heart failure may be difficult. If there is substantial orthopnoea, suspect that heart failure is a significant component, and if the ejection fraction is reported to be normal, DD is likely. If available, B-type natriuretic peptide levels may be invaluable in making the diagnosis in such circumstances. High levels of BNP are equally common in systolic heart failure and diastolic failure.

The big question is "What about those who have both diastolic dysfunction and impaired systolic function"? It may well turn out that the most important predictor of effort tolerance in patients with systolic dysfunction is in fact diastolic dysfunction ! There is emerging evidence that myocardial remodelling (and consequent diastolic dysfunction) is far more important in the pathogenesis of heart failure, than is systolic function. Just because systolic function is relatively easily assessed doesn't mean that it's important!

Bibliography

A really good PDF text is that by JRTC Roelandt & M Pozzoli. ( http://www.gulfheart.org/magazine/H.V._VOL.2_3_AUTUMN_2001.pdf#page=31). This can be found elsewhere in hypertext format.

Other (nonce) references are scattered throughout the text.