JACC: CARDIOVASCULAR IMAGING

VOL. 8, NO. 5, 2015

ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 1936-878X/$36.00

PUBLISHED BY ELSEVIER INC.

http://dx.doi.org/10.1016/j.jcmg.2015.02.004

EDITORIAL COMMENT

In Pursuit of the Holy Grail* Petros Nihoyannopoulos, MD

I

maging of the right ventricle (RV) has gained popularity.

Terms

such

as

“the

adults (4). These do not include ejection fraction but

forgotten

rather a number of linear parameters, the most pop-

ventricle” or “difficulties in assessing RV func-

ular being the longitudinal motion by M-mode of the

tion attributed to its shape” are frequently used as

tricuspid annular excursion (TAPSE). TAPSE is easily

opening statements in new research. Two things

obtainable and is a measure of RV longitudinal func-

make the RV challenging to assess by any imaging

tion. Although it only measures tricuspid annular

modality: the thin wall and the overall asymmetric

excursion and therefore the RV inflow track alone,

shape in the form of a crescent shell covering part

it has shown good correlation with radionuclide-

of the left ventricle. The RV has also an anatomically

derived RV ejection fraction (5) and is recommended

distinct inflow and outflow that are placed in

by the joint ASE/EAE guidelines for routine use (4).

different planes.

The main disadvantage, however, is that TAPSE as-

What is important in diagnostic imaging is the

sumes that the displacement of a single segment

ability to link patterns or numbers to clinical out-

(tricuspid annulus) represents the overall function of

comes. While “a pretty picture is worth a thousand

a complex structure, and there are no large-scale

words” holds true, the 5 general rules for a diag-

validation studies for this.

nostic test to be clinically useful are: to be feasible

It

is

only

with

the

recent

development

of

for most patients, to be noninvasive (including

3-dimensional (3D) echocardiography that attempts

absence of ionizing radiation), to be consistent

to estimate RV ejection fraction by echocardiography

between and within observers, to be cost-effective,

have re-emerged. As expected, all comparisons have

and to be linked to clinical outcomes. Cardiac mag-

been made against CMR (6–9), and normal reference

netic resonance (CMR) generally fulfills most of those

values have been published (10). The use of 3D

criteria and is probably cost-effective in the assess-

echocardiography for valve disease and also for the

ment of RV function, for this it is widely perceived as

assessment of left and right ventricular function is

the reference method.

rapidly gaining acceptance, and guidelines have

RV ejection fraction provides substantial func-

been reported (11). In expert hands, 3D has become a

tional and prognostic information (1,2). This, until

credible alternative to CMR for assessing RV volumes

recently, could only be determined by CMR or radio-

albeit with some negative bias as indeed for the left

nuclide angiography with some accuracy. Two-

ventricular volumes calculations.

dimensional echocardiography cannot assess RV

But is assessing RV volumes what we should be

ejection fraction and instead, several other surrogate

doing in functional RV assessment? Until now we had

parameters have been advocated (3). Recently, a joint

nothing else. There is no doubt that ejection fraction

effort between the American Society of Echocardiog-

is the best we can do today, and it is linked to out-

raphy (ASE) and the European Association of Echo-

comes. Ventricular volume calculations are notori-

cardiography (EAE) published guidelines for the

ously bad and are load dependent. Reproducibility

echocardiographic assessment of the right heart in

varies among imaging techniques from 10% to 20% (and possibly more). Volume calculations have been used because they are easily derived and there has

*Editorials published in JACC: Cardiovascular Imaging reflect the views of

been little or no alternative. But there is more to

the authors and do not necessarily represent the views of JACC:

phenotyping heart disease, as CMR has shown, that

Cardiovascular Imaging or the American College of Cardiology.

may be prognostically but also therapeutically more

From

exciting, namely, the detection and quantification of

the

Department of

Cardiology, Imperial

College London,

Hammersmith Hospital, London, United Kingdom; and the University of Athens, Ippokrateion Hospital, Athens, Greece. Dr. Nihoyannopoulos has reported that he has no relationships relevant to the contents of this paper to disclose.

myocardial fibrosis (12). Myocardial fibrosis leads to impaired cardiac diastolic and systolic function and is related to adverse

524

Nihoyannopoulos

JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 5, 2015 MAY 2015:523–5

Editorial Comment

fibrosis,

cardiovascular events (13,14). Most of the studies,

histology

however, are single-center and suffer from referral

the findings with 2-dimensional strain by speckle

bias. In the recent European Guidelines for Patients

tracking echocardiography. The unique advantage

With Hypertrophic Cardiomyopathy, CMR with late

of this study is that the authors could look at tissue

gadolinium enhancement is a class IIa level B cate-

samples of the RV free wall obtained from explan-

gory for the assessment of cardiac anatomy and

ted hearts. Histology was performed from 3 full-

ventricular

thickness slices of the RV at basal, mid-, and api-

function

and

for

the

detection

of

myocardial fibrosis (15).

RV

free

wall

comparing

cal levels. Fibrosis was calculated as an average of

Myocardial strain calculation is a relatively novel way to assess ventricular function. It provides angleindependent

for

assessment

of

regional

the 3 slices. All patients were studied as part of their trans-

myocardial

plantation work-up including electrocardiography,

deformation and does not rely on geometric as-

cardiopulmonary exercise testing, and NT-pro-BNP

sumptions (16). Longitudinal strain can quantify

assays. A comprehensive echocardiographic assess-

systolic function, allows for the evaluation of regional

ment included a number of standard parameters as

and global deformation properties of the myocar-

recommended by the ASE/EAE guidelines, including

dium, and may be a more sensitive method to identify

TAPSE, RV sphericity, right atrial (RA) function, as

subclinical left ventricular dysfunction (17). An

well as RA longitudinal stain. Seventeen (63%) pa-

important study by Urbano-Moral et al. (18) showed

tients had severe RV myocardial fibrosis defined as

an association between myocardial fibrosis detected

>50% of myocardium. Not surprisingly, all echocar-

by CMR and regional effect on myocardial function.

diographic parameters were also reduced. The major

Myocardial segments with hypertrophy and fibrosis

finding of this study, however, was that RV fibrosis

had the most impaired regional function by all

clearly correlated with free wall longitudinal strain

deformation parameters.

and oxygen consumption (VO 2) max, but poorly

More recently, studies using myocardial strain of

correlated with TAPSE and RA longitudinal strain. RV

the RV have shown that RV systolic strain is a

free wall longitudinal strain was the main determi-

powerful predictor of clinical outcome of patients

nant of myocardial fibrosis and predicted the limited

with known or suspected pulmonary hypertension

exercise tolerance. Because of the nature of the study,

(19,20). This is potentially a breakthrough method

they were unable to ascertain the relationship be-

considering the thin-walled RV, which could be

tween alterations of RV free wall longitudinal strain

challenging to assess with any imaging modality.

and disease progression from subclinical disease to

More recently, we used 3D strain in patients with

severe RV dysfunction.

pulmonary arterial hypertension and found that

The study has also a number of limitations. The

reduced area strain (AS), longitudinal strain, and

etiology of RV dysfunction and fibrosis was sec-

circumferential

with

ondary to left heart disease of variable etiologies

increased mortality risk (21). The new measurement

strain

were

all

associated

(mostly ischemic [59%]), idiopathic cardiomyopathy

of AS had strong associations with RV ejection frac-

(37%), and 1 hypertrophic cardiomyopathy so that

tion, whereas only AS was an independent predictor

most if not all would have had secondary (post-

of death on multivariable analysis, suggesting the

capillary) pulmonary hypertension. These left heart

superiority of 3D–derived AS over other variables.

conditions

Normal values for RV strain have also been published

fibrosis of the left ventricle and therefore relating

(22), thus moving a step closer to establishing strain

with other patients’ clinical data may not be valid.

as a valuable alternative to RV assessment.

The echo analysis was performed by excluding the

SEE PAGE 514

are

also

responsible

for

myocardial

ventricular septum, which is a good thing as its inclusion would have diluted their data because it

In this issue of iJACC, Lisi et al. (23) provide

would contain left heart abnormalities. The authors

new information regarding the correlation between

studied patients with end-stage heart failure with

myocardial strain as assessed by echocardiography

marked RV enlargement. In other words, they

and myocardial fibrosis quantified histologically.

studied the worst of the worst scenarios, and it is

This is a significant study because until now

not possible to extrapolate to patients with less se-

most correlations were made against surrogate

vere heart failure or patients with precapillary pul-

techniques for myocardial fibrosis, such as late

monary hypertension. Finally, they do not provide

gadolinium enhancement using CMR. The authors

any information about cardiac arrhythmias. Studies,

examined 27 patients with end-stage heart failure

particularly in cardiomyopathy patients, have shown

undergoing cardiac transplantation and looked at

an association between fibrosis (assessed by CMR)

Nihoyannopoulos

JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 5, 2015 MAY 2015:523–5

Editorial Comment

and arrhythmia. It would have been of interest for

value of advancing fibrosis on RV strain in patients

the authors to show us the extent of fibrosis by

with pulmonary hypertension.

disease, but the number of patients would have REPRINT REQUESTS AND CORRESPONDENCE: Dr.

been limited. So, is assessing RV fibrosis the holy grail of RV

Petros Nihoyannopoulos, Department of Cardiology,

imaging? These data do not provide sufficient sup-

Imperial

port, but it is clearly a step forward to encourage

Hospital, DuCane Road, London W12 0NN, United

College

London,

NHLI,

Hammersmith

further prospective studies looking at the predictive

Kingdom. E-mail: [email protected].

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KEY WORDS heart failure, myocardial fibrosis, right ventricle

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In pursuit of the holy grail.

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