Diastolic Stress Test

JACC: CARDIOVASCULAR IMAGING

VOL.

-, NO. -, 2019

ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

STATE-OF-THE-ART PAPER

Diastolic Stress Test Invasive and Noninvasive Testing Jong-Won Ha, MD, PHD,a Oyvind S. Andersen, MD,b Otto A. Smiseth, MD, PHDb

ABSTRACT Diastolic dysfunction is a key factor in the pathogenesis of heart failure. Around 50% of cases of heart failure, the hemodynamic correlate of which is increased left ventricular filling pressure, are caused by diastolic dysfunction in the setting of apparently normal systolic function. Due to its high prevalence, diastolic dysfunction is often recognized as an incidental finding. Many patients have Doppler echocardiographic evidence of impaired diastolic function but do not have any symptoms of heart failure at rest. In many of these patients, symptoms of diastolic dysfunction occur only during exercise, as left ventricular filling pressure is normal at rest, but increases with exercise. This implies that filling pressures should also be measured during exercise. The diastolic stress test refers to the evaluation of diastolic function, either invasively or noninvasively, during exercise. This review focuses on the clinical need for diastolic stress testing, both invasively and noninvasively. (J Am Coll Cardiol Img 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.

I

t has become increasingly evident that abnor-

may have entirely normal diastolic hemodynamics

malities of diastolic function play a major role

assessed in the resting state, and in these patients,

in precipitating heart failure and determining

filling pressures must be measured also during exer-

prognosis (1–4). Primary diastolic dysfunction is the

cise. Diastolic dysfunction can be graded using echo-

cause of up to 50% of cases of heart failure, the hemo-

cardiography. In patients with grade I diastolic

dynamic correlate of which is increased filling pres-

dysfunction, LV filling pressure at rest is normal.

sures.

this

However, in patients with a similar grade of diastolic

abnormality is often recognized as an incidental

dysfunction at rest, there can be a spectrum of alter-

finding. Many elderly subjects and patients with hy-

ations in diastolic function during exercise (Figure 1).

pertension or left ventricular (LV) hypertrophy have

Therefore, exercise could unmask diastolic abnormal-

Doppler echocardiographic evidence of impaired dia-

ities not evident under rest conditions. Despite this,

stolic function but do not have any symptoms of heart

the majority of measures used to characterize the

failure at rest. In many of these patients, symptoms of

severity of heart failure and prognosis are obtained

diastolic dysfunction occur only during exercise. In

at rest.

However,

because

of

its

ubiquity,

these patients, LV filling pressure can be normal at

Exertional dyspnea is among the most common

rest, but it increases with exercise, as they are unable

presenting symptoms in our routine practice. How-

to increase cardiac output without increasing filling

ever, the mechanisms responsible for dyspnea may

pressure. Thus, patients with significant heart disease

vary in different conditions. Although cardiac or

From the aDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; and the bDepartment of Cardiology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway. Dr. Ha was supported by the Bio and Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science and Information Communication Technology (2016M3A9E9941746). Dr. Andersen was funded by South-Eastern Norway Regional Health Authority (project 2014068). Dr. Smiseth has reported that he has no relationships relevant to the contents of this paper to disclose. Manuscript received September 4, 2018; revised manuscript received January 16, 2019, accepted January 16, 2019.

ISSN 1936-878X/$36.00

https://doi.org/10.1016/j.jcmg.2019.01.037

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Diastolic Stress Test

ABBREVIATIONS

pulmonary diseases are major causes of

etiology of dyspnea and thus LV filling parameters are

AND ACRONYMS

pathologic dyspnea, other systemic condi-

often overlooked. More importantly, patients who

tions, such as anemia, obesity, and neuro-

have exertional dyspnea that cannot be explained by

muscular diseases, should also be suspected.

the variables of LV systolic and diastolic functions at

By accurately identifying the correct cause of

rest would have steep LV pressure-volume relations

dyspnea in a patient, the appropriate treat-

in diastole during exercise compared with those who

ment can be implemented. A comprehensive

have no symptoms of exertional dyspnea despite

history, physical examination, and basic

similar LV diastolic functions at rest. If this is true,

laboratory tests are important in the initial

exercise hemodynamic responses, rather than evalu-

assessment; however, the diagnosis may

ation of diastolic function at rest alone, would pro-

depend on more specialized testing. Cardiac

vide

causes of dyspnea include right, left, or

information about these patients. Therefore, for pa-

biventricular heart failure with systolic dysfunction;

tients who report severe exertional symptoms, it may

coronary artery disease; recent or remote myocardial

be desirable to measure the hemodynamic response

infarction; hypertension with LV hypertrophy; car-

to exercise to ensure that these symptoms are due to

diomyopathy; valvular dysfunction; pericardial dis-

circulatory dysfunction.

eases; arrhythmia; and congenital heart disease. In

INVASIVE DIASTOLIC STRESS TEST. LV diastolic

these disorders, diastolic dysfunction often occurs in

pressure is the main parameter that characterizes LV

combination with systolic dysfunction. In some cases,

filling properties. The term LV filling pressures can

however, such as conditions with LV hypertrophy and

refer to mean pulmonary capillary wedge pressure

normal ejection fraction (EF), diastolic dysfunction is

(PCWP), mean left atrial (LA) pressure, LV pre-A

the main contributor to heart failure symptoms.

pressure, mean LV diastolic pressure, and LV end-

Regardless of EF, elevated LV filling pressure is the

diastolic pressure (5,6). In the early stages of dia-

most important hemodynamic parameter to explain

stolic dysfunction, only LV end-diastolic pressure is

symptoms of dyspnea. However, many clinicians

the only abnormally elevated pressure, whereas mean

utilize echocardiography mainly to assess LV volumes

PCWP and LA pressure remain normal. With tachy-

and EF in trying to draw conclusions about the

cardia and/or increased LV afterload, mean PCWP and

EF = ejection fraction LA = left atrial LV = left ventricular PCWP = pulmonary capillary wedge pressure

PH = pulmonary hypertension SPAP = systolic pulmonary artery pressure

TR = tricuspid regurgitation

additional

physiological

and

diagnostic

LA pressure increase, providing the basis for the diastolic stress test. Catheterization is performed F I G U R E 1 Hemodynamic Response to Exercise

while subjects are doing exercise on a variable load ergometer bicycle specially mounted at the catheter-

8

ization table in a supine position. Changes of PCWP,

A

an indirect estimate of LV diastolic pressures, during

Cardiac Index (L/min/m2)

Exercise

exercise can be assessed by right heart catheteriza-

6

tion through the right internal jugular vein. Alternately, LV diastolic pressures at rest and during

B 4

exercise can be obtained by introducing a pigtail catheter into the LV from a radial arterial access site. More accurately, instead of fluid-filled pigtail catheter, a high-fidelity pressure wire can be introduced

2

into the LV through a 5-F multipurpose catheter. For

Rest

this measurement, the pressure wire should be calibrated before and after exercise to confirm the correct operation of the device without losing its calibration

0 0

10

20

30

PCWP (mm Hg)

during measurements. By this approach, LV systolic pressure, minimal LV pressure, LV end-diastolic pressure, and mean LV diastolic pressures can be

Changes of cardiac output and pulmonary capillary wedge pressure pres-

measured. The dP/dt max and dP/dtmin can also be

sures (PCWP) during exercise. Patients A and B have almost identical left

automatically traced and the time constant of LV

ventricular filling pressures and cardiac index at rest. In Patient A, there is a significant increase in cardiac index with a small change in left ventricular filling pressure (normal response), whereas in Patient B, there is a sig-

relaxation, tau, can be computed (7). This approach has an important advantage because it allows the

nificant increase in left ventricular filling pressure but smaller increase in

assessment of change in minimal LV pressure during

cardiac index during exercise.

exercise. Previous studies utilizing an invasive measurement

of

LV

pressure

demonstrate

that

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F I G U R E 2 LVP at Rest and During Exercise

A LV Pressure (mm Hg)

At Rest

At 75 W of Exercise

150

150

100

100

50

50

0

0 Minimal LVP at Rest

B LV Pressure (mm Hg)

At Rest

At 75 W of Exercise

120

120

80

80

40

40

0

0 Minimal LVP at Rest

Representative cases of left ventricular pressure (LVP) curves at rest and at maximal exercise from 2 individuals. In patient A, minimal LVP at rest was
1.0 mm Hg and decreased to
5.4 mm Hg during maximal exercise. In patient B, minimal LVP at rest was
1.0 mm Hg and increased to 15.5 mm Hg during exercise.

augmenting LV suction is important to produce the

Thus, a decrease in minimal LV pressure reflecting

early diastolic mitral valve gradient for more rapid

the augmented LV suction during exercise is crucial

mitral valve flow in early diastole, particularly during

to maintain early LV diastolic filling without an in-

exercise, which shortens the diastolic period (8,9).

crease in LA pressure.

T A B L E 1 Summary of the Studies Validating Noninvasive Diastolic Stress Testing

Study design Population

Burgess et al., 2006 (18)

Talreja et al., 2007 (10)

Obokata et al., 2017 (11)

Prospective

Prospective

Prospective

Hong et al., 2018 (7)

Prospective

Unselected patients

Exertional dyspnea

50 HFpEF, 24 noncardiac dyspnea

Asymptomatic previous PCI

Study patients, n

37

12

74

21

Mode of exercise

Supine bicycle

Supine bicycle

Supine bicycle

Supine bicycle

Parameter of LV filling pressure during exercise

Mean LVDP

PCWP

PCWP

DLV minimal pressure

Parameter of noninvasive LV filling pressure during exercise

E/e0 medial

E/e0 medial

E/e0 medial

DE/e0 medial

Sensitivity/specificity for identifying elevated LV filling pressure, %

73/96

89/100

—

—

Correlation coefficient

0.59

—

0.57

0.51

HFpEF ¼ heart failure with preserved ejection fraction; LVDP ¼ left ventricular diastolic pressure; PCI ¼ percutaneous coronary intervention; PCWP ¼ pulmonary capillary wedge pressure.

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C E N T R A L IL L U ST R A T I O N Noninvasive Diastolic Stress Test

Ha, J.-W. et al. J Am Coll Cardiol Img. 2019;-(-):-–-.

(A) Illustrative photo of a noninvasive diastolic stress test using echocardiography. (B and C) Diastolic stress echocardiographic data acquired before and after symptom-limited supine bicycle exercise in 2 individuals with impaired relaxation and almost identical mitral inflow and annular velocities at rest. In Patient B, there is a concordant rise in both mitral E velocity and mitral annular e0 velocity with exercise, without an overall change in mitral E/e0 ratio. In Patient C, there is an increase in mitral E velocity but minimal change in e0 with exercise, resulting in increased E/e0 , suggestive of elevated left ventricular filling pressures with exercise.

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A normal heart can increase transmitral flow during exercise with little or no increase in LA pressure

F I G U R E 3 Response in Mitral Inflow and Annular Velocities During Exercise

by lowering minimum LV diastolic pressure. In the

Baseline

failing heart, there is no fall in minimum LV diastolic

25 W

50 W

pressure with exercise, and thus the increase in transmitral gradient and flow is achieved by elevation of LA pressure. Possibly, a similar mechanism explains the elevated LA pressure found during exercise in patients with heart failure. Representative cases of

Mitral Flow

LV pressure curves at rest and at maximal exercise from 2 individuals are shown in Figure 2. Minimal LV pressure at rest was
1.9 mm Hg and decreased to
5.4 mm Hg during maximal exercise in Patient A, whereas minimal LV pressure at rest was 6.5 mm Hg

Mitral Annulus

and increased to 15.5 mm Hg in Patient B. Although cardiac catheterization remains the gold standard and provides several important hemodynamic parameters, it is not practical to submit all patients presenting with dyspnea and suspicion of HF

Diastolic stress echocardiographic data acquired before and at 2 levels of symptom-

to invasive studies. Thus, a noninvasive way to esti-

limited supine bicycle exercise in a 79-year-old woman with exertional dyspnea. Mitral

mate LV filling pressure during exercise is highly desired and forms the rationale behind the develop-

flow pattern at baseline showed normal looking mitral inflow pattern. However, following exercise, there is an exaggerated increase in mitral E velocity but minimal change in e0 , suggestive of elevated left ventricular filling pressures with exercise.

ment of the diastolic stress test. A simultaneous echocardiographic-catheterization

study

prospec-

tively conducted at rest and during exercise in sub-

exercise in normal subjects (16), but E/e 0 is expected

0

to increase with exercise in patients with myocardial

jects with exertional dyspnea has shown that E/e

provides a reliable estimation of PCWP not only at

disease.

rest but also with exercise (10). Another simultaneous

Diastolic stress echocardiography has been intro-

echocardiographic-catheterization study conducted

duced to detect exercise-induced increase in diastolic

at rest and during exercise in subjects with invasively

filling pressures by performing Doppler echocardiog-

proven heart failure with preserved EF and partici-

raphy during exercise (17). The diastolic stress test

pants with dyspnea but no identifiable cardiac pa-

refers to the use of exercise Doppler echocardiogra-

thology,

demonstrated

that

exercise

E/e 0

data

phy to detect impaired LV diastolic functional reserve

improves sensitivity and negative predictive value,

and the resulting increase in LV filling pressures

and thus these results reinforce the value of exercise

(5,6,17–20) in patients with unexplained dyspnea or

testing using invasive and noninvasive hemodynamic

subclinical diastolic dysfunction (e.g., diabetic car-

assessments to definitively confirm or refute the

diomyopathy, hypertensive patients). Preliminary

diagnosis of heart failure with preserved EF (11).

results showed that diastolic stress echocardiography

NONINVASIVE DIASTOLIC STRESS TEST (DIASTOLIC

is technically feasible for demonstrating the change

STRESS ECHOCARDIOGRAPHY). Invasive hemody-

in E/e0 (i.e., filling pressure) that occurs with exercise

namic monitoring during exercise would be most ac-

and that the hemodynamic consequences of exercise-

curate (11), but a noninvasive demonstration of this

induced increase in LV filling pressure can be

phenomenon would be more practical and clinically

demonstrated noninvasively with this novel tech-

applicable.

nique (Table 1). This test has the potential to distin-

It has been shown and validated that LV filling

guish between cardiac and noncardiac dyspnea in

pressures can be estimated by combining mitral

patients with multiple coexisting conditions causing

inflow (E) and mitral annulus (e 0 ) velocities recorded

exertional dyspnea (21).

with Doppler and tissue Doppler echocardiography,

Diastolic stress echocardiography can be per-

respectively (12–14). E and e 0 velocities increase pro-

formed using either a supine bicycle or treadmill ex-

portionally as transmitral gradient increases in sub-

ercise protocol. Of the 2 methods, exercise using a

jects with normal myocardial relaxation, whereas e0

supine bicycle is the recommended modality for dia-

velocity does not change as much as E velocity in

stolic stress echocardiography because it allows the

patients with abnormal myocardial relaxation (15). As

acquisition of Doppler recordings throughout the test

a result, E/e 0 remains essentially unchanged with

and

thus

noninvasive

assessment

of

exercise

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F I G U R E 4 Exercise-Induced PH

Patient A

25 W

Baseline

Patient B Baseline

75 W

50 W

Mitral Flow

25 W

50 W

Mitral Flow

Mitral Annulus

Mitral Annulus

Baseline

25 W

2.4 m/s

3.0 m/s

75 W

Baseline

25 W

4.0 m/s

2.3 m/s

4 m/s

50 W

3.4 m/s

50 W

4 m/s

Diastolic stress echocardiographic data acquired before and at 2 levels of symptom-limited supine bicycle exercise in 2 individuals with exertional dyspnea. Both patients showed increase in tricuspid regurgitation velocity during exercise, suggestive of exercise-induced pulmonary hypertension (PH). In Patient A, there is a concordant rise in both mitral E velocity and mitral annular e0 velocity with exercise, without an overall change in mitral E/e0 ratio, indicating normal left ventricular filling pressure during exercise. In Patient B, there is an exaggerated increase in mitral E velocity but minimal change in e0 during exercise. Thus, the E/e0 ratio increases, suggestive of elevated left ventricular filling pressures with exercise.

diastolic function indices. Treadmill exercise stress

this filling pattern is typical for mild diastolic

echocardiography is an alternative as diastolic ab-

dysfunction. It is recognized as an early manifesta-

normalities normally persist even after cessation of

tion in the spectrum of diastolic abnormalities. Dur-

exercise. In supine bicycle exercise, the workload

ing exercise, there is less time for diastolic filling of

starts at 25 W and increases in increments of 25 W

the LV, as tachycardia decreases the duration of

every 3 min. Mitral inflow by pulsed Doppler echo-

diastole. To maintain or augment stroke volume,

cardiography at the level of mitral tips, mitral annular

myocardial relaxation rate should increase and LV

velocities by spectral Doppler echocardiography, and

suction should be exaggerated. It is not yet known

tricuspid

continuous-wave

whether impaired LV relaxation leads invariably to

Doppler should be recorded at baseline, during exer-

elevated LV filling pressure during exercise, as pa-

cise, and in the recovery period after termination of

tients with a similar grade of diastolic dysfunction at

exercise.

rest present a spectrum of alterations in diastolic

regurgitation

jet

by

Impaired myocardial relaxation is reflected in

function during exercise. Stress echocardiography

reduced early (E) to late (A) diastolic filling velocity

Doppler data acquired before and after symptom-

ratio or prolonged deceleration time of E velocity, and

limited supine bicycling performed in 2 individuals

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F I G U R E 5 Interpretation of Mitral Inflow and Annular Velocities During Exercise

Baseline

25 W

Recov 2 min

13

15

19

Mitral Flow

Mitral Annulus

E/e’

The following case illustrates mitral inflow and annulus velocity pattern in a 56-year-old woman with exertional dyspnea. Because of premature tachycardia even with mild exercise, accurate measurement of mitral flow and annular velocities were not possible beyond 25 W of exercise. However, mitral flow and annular velocities at 2 min after cessation of exercise showed separation of mitral inflow E and A velocities and mitral annular e0 and a0 velocities. E/e0 in the recovery period was significantly increased and higher than at rest and at 25 W of exercise, suggesting persistent elevation of left ventricular filling pressure in the recovery period.

with impaired relaxation and almost identical mitral

with exertional dyspnea. Mitral flow pattern at base-

inflow and annular velocities at rest are shown in the

line showed normal-looking mitral inflow pattern.

Central Illustration. In Patient B, there is a concordant

However, following exercise, there is an exaggerated

rise in both mitral E velocity and mitral annular e 0

increase in mitral E velocity but minimal change in e 0 ,

velocity with exercise, without an overall change in

suggestive of elevated LV filling pressures with ex-

mitral E/e0 ratio. In Patient C on the other hand, there

ercise (Figure 3).

is an increase in mitral E velocity but minimal change

Interpretation and hemodynamic correlation. In healthy

in e 0 with exercise, suggestive of elevated LV filling

subjects, the E/e 0 ratio does not change significantly

pressures with exercise. These cases further under-

with exercise because of proportional increases in

score the need for assessing hemodynamic perfor-

both the mitral inflow and annular velocities (16);

mance using diastolic stress echocardiography. It is

this represents the normal diastolic response for

useful to further characterize these patients because

exercising subjects. Conversely, an increase in the E/

exercise could unmask diastolic abnormalities not

e0 ratio and/or systolic pulmonary artery pressure

evident under rest conditions despite similar resting

(SPAP) with exercise has been shown to parallel in-

mitral inflow and annular velocities.

creases in the LV diastolic pressures as recorded by

The diastolic stress test is not only useful in pa-

invasive measurements (18). The diastolic stress

tients with mild diastolic dysfunction with impaired

echocardiography is definitively normal if the septal

relaxation. It can also delineate an abnormal response

E/e 0 is <10 at rest and with exercise, and the peak

during exercise in subjects with normal mitral inflow

tricuspid regurgitation (TR) velocity is <2.8 m/s at

at rest. The following case illustrates mitral inflow

rest and with stress. A study is definitively abnormal

and annulus velocity pattern in a 79-year-old woman

when the septal E/e 0 ratio is >15, average E/e 0 is >14,

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and diastolic reserve are both associated with exercise

F I G U R E 6 Changes of Minimal LVP and Velocity of Apical Untwisting

capacity, but E/e0 has greater specificity for elevated

(Backrotation) With Exercise

filling pressure and is more closely associated with the expected parameters of diastolic dysfunction. How-

–50

r = 0.687, P = 0.028

ever, the high sensitivity of diastolic reserve makes it a better test for screening for exercise-induced dia-

Minimal Apical Back-Rotation Velocity at 50 W of Exercise (Degrees/s)

8

Suction (–)

–100

stolic dysfunction (25). Exercise-induced

LV

filling

pressure

elevation

and

exercise-induced PH. Exercise-induced PH is common in subjects with reduced as well as preserved LVEF (26) and is considered as an important cause of ex-

–150

ertional dyspnea and exercise intolerance (26,27). Figure 4 illustrates a diastolic stress echocardiography acquired before and after a symptom-limited supine

Suction (+)

–200

bicycle exercise in 2 individuals with exertional dyspnea. Both patients showed increase in TR velocity during exercise, suggesting exercise-induced PH. In patient A, there is a concordant rise in both mitral E

–250

velocity and mitral annular e 0 velocity with exercise, 0

–5

5

10

20

15

ΔMinimal LVP (mm Hg)

without an overall change in mitral E/e0 ratio. In the patient B, following exercise, there is an exaggerated increase in mitral E velocity but minimal change in e0 . Thus, the E/e0 ratio increases, suggestive of elevated

Patients with a preserved LV suction during exercise showed marked increase in LV untwisting velocity with exercise whereas patients without LV

LV filling pressures with exercise. A previous study

suction during exercise showed minimal increase in LV untwisting velocity

has shown that subjects with exercise-induced PH

with exercise. LVP ¼ left ventricular pressure.

associated with an increase in E/e 0 had significantly worse outcomes than subjects without exerciseinduced PH, whereas no significant difference of

peak TR velocity is >2.8 m/s with exercise, and 0

when either the septal e velocity is <7 cm/s or the 0

clinical outcomes were found between subjects with exercise-induced PH without an increase in E/e 0 and

lateral e velocity is <10 at baseline (5,6,19,20). SPAP

subjects without exercise-induced PH (28). Thus,

measurement with exercise has been found to be

exercise-induced PH secondary to an increase in LV

helpful in aiding the assessment of diastolic filling

filling portends poorer clinical outcome. Therefore,

pressure with exercise. It has been shown that the

preventing or treating exercise-induced PH should be

<35

rest

focused on improving LV diastolic properties and

and <43 mm Hg at exercise. Exercise E/septal e >13,

decreasing the LV filling pressure at rest and during

lower amplitude of changes in diastolic longitudinal

exercise. Diastolic stress echocardiography has a sig-

velocities, and induced pulmonary hypertension

nificant role in this regard, as it can provide infor-

(PH) (SPAP $50 mm Hg) are markers of adverse

mation regarding SPAP as well as LV filling pressure

outcomes.

both at rest and during exercise.

Detection of early myocardial disease and concept of

Technical challenges. One of the practical drawbacks

diastolic reserve. Different raises of e0 during exercise,

of diastolic stress echocardiography is technical

upper

normal

SPAP

is

mm

Hg

at 0

quantified by longitudinal functional reserve, can be

difficulty in obtaining adequate 2-dimensional and

used as a parameter to evaluate LV diastolic reserve

Doppler

during exercise. Longitudinal diastolic functional

limited time particularly during exercise. Fortu-

reserve can be calculated as follows: D e 0 [1
(1 / e 0 base )],

nately, patients with marked diastolic dysfunction

where D e 0 is the change of e0 from baseline to 25 or 50 W

revealed diagnostic changes even at mild or mod-

of exercise, and e 0 base is early diastolic mitral annular

erate exertion with moderately increased heart rate.

velocity at rest (22). LV diastolic reserve is reported to

Despite this, a subset of patients develop premature

be reduced in various diseases that are associated with

tachycardia even at mild exertion, which makes a

echocardiographic

parameters

within

diastolic dysfunction, including hypertrophic cardio-

meaningful analysis difficult, as there will be fusion

myopathy, diabetes mellitus, and a subtype of hyper-

of the mitral inflow E and A signals, as well as of

tension (22–24). It has been shown that exercise E/e 0

the mitral annular e 0 and a 0 signals. In a previous

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report (17), the test was unsuccessful in 10% of

FUTURE DIRECTIONS. Most of the previous studies

enrolled patients because of tachycardia with low

regarding diastolic stress echocardiography excluded

atrial

patients with significant coronary artery disease to

tachyarrhythmia. It has been shown that diastolic

avoid confounding effects from myocardial ischemia

dysfunction induced by exercise or ischemia per-

to the evaluation of diastolic function (17,18,22,23).

sists after recovering from myocardial ischemia or

However, in our clinical practice, patients with sig-

cessation of exercise (29). In a preliminary study, 73

nificant coronary artery disease with or without

healthy subjects underwent supine bicycle exercise

myocardial ischemia would be an important subset of

and mitral inflow parameters and diastolic velocities

patients in whom the assessment of exercise-induced

of the mitral annulus were recorded at baseline and

increase in LV filling pressure would be critically

during recovery 2, 5, and 10 min after cessation of

important. Future studies are warranted to clarify

exercise. None of the patients had E/e 0 >15 at rest,

this issue. Because the clinical value of diastolic

during exercise, or in the recovery phase for up to

stress echocardiography has been verified mostly

10 min after cessation of exercise (30). Because E/e 0

from patients with preserved LV systolic function,

was not elevated in healthy subjects, elevated E/e0

there is so far limited experience for applying this

during recovery may be helpful to detect exercise-

technique to patients with regional LV dysfunction,

induced

mitral valve disease, and atrial fibrillation.

levels

of

exercise

diastolic

and

exercise-induced

dysfunction

in

subjects

with

tachycardia even at low levels of exercise. Thus, if

Recently, it was shown that absence of a decrease

the evaluation of mitral inflow and annular veloc-

in minimal LV pressure during exercise, a manifes-

ities during exercise is not optimal due to prema-

tation of impaired LV suction, was closely linked with

ture tachycardia, another way is to evaluate these

impaired LV untwisting during exercise (7). In pa-

parameters in the recovery period after cessation of

tients with normal LVEF, previously treated for cor-

exercise. Figure 5 illustrates the mitral inflow and

onary artery disease, we have shown a range of

annular velocity pattern in a 56-year-old woman

responses when measuring minimum LV diastolic

with exertional dyspnea. Because of premature

pressure, tau, and untwisting velocity. Patients with a

tachycardia even with mild exercise, accurate mea-

decrease in minimum LV diastolic pressure had the

surement of mitral flow and annular velocities were

most marked increase in LV untwisting velocity with

not possible beyond 25 W of exercise. However, mitral flow and annular velocities obtained 2 min after cessation of exercise showed separation of

HIGHLIGHTS

mitral inflow E and A velocities and mitral annular

 Diastolic dysfunction is a key factor in the pathogenesis of heart failure.

e0

and a0

velocities. More strikingly, E/e 0

was

significantly higher than at rest and during 25 W of exercise,

suggesting

persistent

elevation

of

LV

filling pressure even at recovery period. DIASTOLIC STRESS TEST IN RECENT GUIDELINES.

Recently, guidelines from the American Society of Echocardiography/European Association of Cardiovascular Imaging regarding the evaluation of LV diastolic function by echocardiography (5,6) and clinical use of stress echocardiography in nonischemic heart disease (19,20) included diastolic stress echocardiography as a valuable tool for the evaluation of patients with unexplained dyspnea and subclinical LV diastolic dysfunction. These guidelines came at the 11th anniversary of the first feasibility study of diastolic stress echocardiography after the initial description of the normal values of diastolic echocardiographic parameters with exercise in a middle-aged, healthy control subject 1 year earlier. With recent recommendations from the guidelines, it is evident that the time has come for its integration into clinical practice to provide this valuable diagnostic test to our patients (31).

 Frequently, symptoms of diastolic dysfunction occur only during exercise, as LV filling pressure is normal at rest, but increases with exercise.  This implies that LV filling pressures should also be measured not only at rest but also during exercise.  The diastolic stress test refers to the evaluation of diastolic function, either invasively or noninvasively, during exercise, and it will provide insights into cardiovascular hemodynamics.  More work is needed to refine and standardize the methodology but the integration of diastolic stress testing into clinical practice will certainly enhance our understanding and better management of patients with diastolic dysfunction and exertional dyspnea.

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exercise (Figure 6). Furthermore, e0 velocity during

The decades of investigation into the diastolic

exercise was highest in patients with a simultaneous

stress

decrease in minimum LV diastolic pressure. The

wonderful insights into cardiovascular hemody-

change in LV end-systolic volume was similar in pa-

namics and have improved our delivery of care for

tients with a decrease or an increase in LV minimum

patients with diastolic dysfunction and exertional

pressure, suggesting that restoring forces was not

dyspnea. With these efforts and the recommenda-

accounting for the difference in e0 and untwisting

tions from the recent guidelines, it is evident that

velocity. These findings imply that dynamic changes

the integration of diastolic stress testing into clin-

in LV apical back rotation during exercise can be used

ical practice will certainly enhance our under-

as a noninvasive parameter of diastolic suction dur-

standing

ing exercise. More work is needed to refine and

patients’ conditions.

testing

and

have

allow

provided

us

to

us

better

with

many

manage

our

standardize the methodology for measuring twisting deformation, but provided that the technique is

ADDRESS

improved,

Smiseth, Department of Cardiology, Oslo University

untwisting

velocity

may

become

an

FOR

CORRESPONDENCE:

important addition to the diastolic stress echocardi-

Hospital,

ography (32).

E-mail: [email protected].

Rikshospitalet,

N-0027

Dr. Otto A.

Oslo,

Norway.

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KEY WORDS diastolic function, diastolic stress test, heart failure with preserved ejection fraction, stress echocardiography

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