Cardiac Remodeling

JACC: CARDIOVASCULAR IMAGING

VOL. 9, NO. 10, 2016

ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

ISSN 1936-878X/$36.00 http://dx.doi.org/10.1016/j.jcmg.2016.04.006

EDITORIAL COMMENT

Cardiac Remodeling Novel Insights From MESA* Steffen E. Petersen, MD, DPHIL, MPH

C

ardiac

to

Zemrak et al. (2) used MESA’s serial CMR data for

heart failure with substantial mortality,

remodeling

frequently

leads

the first time in 2014 to study cardiac remodeling over

morbidity, and economic burden to society.

a 10-year period. This study demonstrated that more

The prevalence of heart failure is approximately 2%

extensive left ventricular (LV) trabeculation (greater

to 4% of the population in Europe with a major

ratio of noncompacted to compacted layer thickness)

impact on health care expenditure (1). Both the inci-

did not predict the development of clinically signifi-

dence and prevalence of heart failure will increase

cant LV enlargement or systolic dysfunction over a

due to an aging population, an increasing prevalence

decade of follow-up in this asymptomatic cohort.

of diabetes and hypertension, and the improved prog-

These findings are clinically important as they should

nosis of most cardiovascular diseases. Despite the as-

guide clinical decision making in the common sce-

tronomical burden of the disease due to maladaptive

nario where patients with marked LV trabeculation

cardiac remodeling, our current understanding of the

and low pre-test probability of LV noncompaction

interplay of nongenetic and genetic factors contrib-

have no clear need for follow-up imaging or phar-

uting to the remodeling process is still limited. The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study designed to evaluate the

macotherapy. In addition, the Zemrak et al. (2) study already showed that LV volumes reduce over time as people age by 10 years.

mechanisms that lead to the development and pro-

In 2015, Eng et al. (3) confirmed the reduction of LV

gression of subclinical cardiovascular disease. In this

volumes observed by Zemrak et al. (2) and extended

study, 5,004 individuals from 4 ethnic groups

the findings to other LV structural and functional

asymptomatic for cardiovascular disease had a car-

measures. Interestingly, in 2009, Cheng et al. (4)

diac magnetic resonance (CMR) scan at baseline (2000

presented in age-based cross-sectional analyses of

to 2002). Of these participants, 3,016 underwent a

the MESA baseline CMR data, that absolute LV mass

follow-up CMR (2010 to 2012). It is the largest

incrementally decreased across increasing age groups

population-based study to date with serial CMR data

by 0.3 g per year (p < 0.0001), and this trend was

over a decade, which provides tremendous opportu-

observed in both sexes. Eng et al. (3) demonstrated

nities to study influencing factors on cardiac remod-

the importance of longitudinal studies, as longitudi-

eling. Partly due to the open and collaborative study

nal LV mass increase in men was in contrast to the

design with data distribution directly to the study

cross-sectional pattern of LV mass decrease observed

investigators, MESA has recently reached a significant

by Cheng et al. (4). Longitudinally, LV mass decreases

milestone of 1,000 publications from over 2,800

in women, LV end-diastolic volume decreases in men

investigators.

and women, and LV stroke volume and LV mass-tovolume ratio increase in both sexes. Ambale Venkatesh et al. (5) assessed associations

*Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology. From the Department of Advanced Cardiovascular Imaging, William

of changes over 10 years in LV structure and function with myocardial replacement fibrosis (late gadolinium enhancement) and diffuse fibrosis (post-contrast

Harvey Research Institute, National Institute for Health Research

T 1 mapping). The presence of replacement scar after

Cardiovascular Biomedical Research Unit at Barts, London, United

10-year follow-up was temporally associated with 3%

Kingdom. This work forms part of the research contributing to the

decrease in LV ejection fraction and 0.7% greater LV

translational research portfolio of the Cardiovascular Biomedical

end-diastolic volume indexed to body surface area in

Research Unit at Barts, which is supported and funded by the National Institute for Health Research. Prof. Petersen has received consultancy

men only. Diffuse fibrosis after 10-year follow-up was

fees from Circle Cardiovascular Imaging.

longitudinally associated with a decrease in LV mass

Petersen

JACC: CARDIOVASCULAR IMAGING, VOL. 9, NO. 10, 2016 OCTOBER 2016:1174–6

Editorial Comment

indexed to body surface area and reduction in LV

V-shaped relationship between torsion and concen-

ejection fraction (also in men only). Hypertension-

tric hypertrophy and what does it mean? The in-

induced cardiac remodeling was linked to replace-

vestigators offer attempts of explanations. Sex

ment fibrosis, diffuse fibrosis, and hypertrophy.

differences in cardiac remodeling may be related to differences in sex hormones. The initial increase in

SEE PAGE 1164

torsion with increased concentric hypertrophy may

In this issue of iJACC, Yoneyama et al. (6) describe

be due to subendocardial dysfunction with reduced

not only the associations among age, relevant car-

endocardial opposition to the dominant epicardium.

diovascular information including risk factors, and LV

As the concentric remodeling progresses involving

structure and function, but interestingly also the as-

the entire thickness of the myocardium to become

sociations among aging, changes to cardiovascular

dysfunctional, this may then explain the reduced

measures over a decade in the MESA cohort, and

torsion.

changes to CMR measures of cardiac structure and

As Nathaniel Reichek (7) pointed out in an editorial

function. This study confirmed the findings of Eng

on a MESA publication, “Large sample sizes in

et al. (3) that over a period of 10 years, LV end-

multicenter studies combined with improved statis-

diastolic volume and LV ejection fraction decreased,

tical methods have resulted in much greater ability to

whereas LV mass and LV mass-to-volume ratio (a

demonstrate statistically significant associations be-

measure of concentric hypertrophy) increased. Using

tween variables.” Small effect sizes observed in MESA

tagging CMR, they observed that longitudinally

publications summarized in this editorial on assess-

circumferential strain remained unchanged but that

ing longitudinal changes in LV structure and function

torsion increased. Increased LV mass, male sex,

may allow the question of clinical significance of the

increased systolic blood pressure, increased heart

findings. However, the mechanistic insights gleaned

rate, and reduced high-density lipoprotein choles-

from these studies benefit from the greater precision

terol were associated with reduced circumferential

of effect size estimates afforded by the large sample

strain. Individuals who remained on antihypertensive

size. Cardiac remodeling can be assessed accurately

medications over the follow-up of 10 years main-

and precisely by CMR, which provides promising

tained or improved circumferential strain. Yoneyama

surrogate markers for early phase clinical trials (8).

et al. (6) also found a “V-shaped” relationship be-

However, they may even be useful to gain mecha-

tween change in LV mass-to-volume ratio and torsion

nistic insights in large-scale population-based studies

and concluded that increased torsion may be a

as clinical “hard endpoints” of heart failure may not

mechanism to maintain LV systolic function as people

be frequent enough as demonstrated in this MESA

get

remodeling

paper by Yoneyama et al. (6) (only 28 participants had

observed in MESA: effects are in opposing directions

experienced incident heart failure and/or myocardial

for LV mass (in men increases, in women decreases)

infarction over a decade). This lack of hard endpoints

and circumferential strain (in men decreases, in

makes it difficult to answer questions about what

women increases). Effect direction is the same, but

these interesting and complex findings really mean

effect sizes differ by sex for LV end-diastolic volume

for patients.

older.

Sex

affects

the

cardiac

(in women decreases more), LV mass-to-volume ratio (in men increases more), LV ejection fraction (in men

REPRINT REQUESTS AND CORRESPONDENCE: Prof.

decreases more), and torsion (in women increases

Steffen E. Petersen, Department of Advanced Car-

more). The challenge posed by this paper by

diovascular Imaging, William Harvey Research Insti-

Yoneyama et al. (6) is to make sense of the data.

tute,

MESA findings are becoming increasingly complex

Cardiovascular Biomedical Research Unit at Barts,

and thus are not always intuitive: for example, why

Charterhouse Square, London EC1M 6BQ, United

are men and women different? Why is there a

Kingdom. E-mail: [email protected].

National

Institute

for

Health

Research

REFERENCES 1. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA). Eur J Heart Fail 2008;10:933–89.

2. Zemrak F, Ahlman MA, Captur G, et al. The relationship of left ventricular trabeculation to ventricular function and structure over a 9.5-year follow-up: the MESA study. J Am Coll Cardiol 2014;64:1971–80. 3. Eng J, McClelland RL, Gomes AS, et al. Adverse left ventricular remodeling and age

assessed with cardiac MR imaging: the MultiEthnic Study of Atherosclerosis. Radiology 2016;278:714–22. 4. Cheng

S,

Fernandes

VR,

Bluemke

DA,

McClelland RL, Kronmal RA, Lima JAC. Agerelated left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic

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Petersen

JACC: CARDIOVASCULAR IMAGING, VOL. 9, NO. 10, 2016 OCTOBER 2016:1174–6

Editorial Comment

Study of Atherosclerosis. Circ Cardiovasc Imaging 2009;2:191–8. 5. Ambale Venkatesh B, Volpe GJ, Donekal S, et al. Association of longitudinal changes in left ventricular structure and function with myocardial fibrosis: the Multi-Ethnic Study of Atherosclerosis study. Hypertension 2014;64: 508–15.

6. Yoneyama K, Donekal S, Venkatesh BA, et al. Natural history of myocardial function in an adult human population: serial longitudinal observations from MESA. J Am Coll Cardiol Img 2016;9:

8. Pitcher A, Ashby D, Elliott P, Petersen SE. Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints. Heart 2011;97:1286–92.

1164–73. 7. Reichek N. Cor pulmonale parvus: patting the elephant. J Am Coll Cardiol 2014;64:

KEY WORDS aging, left ventricular,

2010–2.

longitudinal study, risk factors, torsion