Ventricular Structure and Function

Right Ventricular Dysfunction Impairs Effort Tolerance

Independent of Left Ventricular Function Among Patients
Undergoing Exercise Stress Myocardial Perfusion Imaging
Jiwon Kim, MD; Antonino Di Franco, MD; Tania Seoane, MD;
Aparna Srinivasan, MBBS, PhD; Polydoros N. Kampaktsis, MD; Alexi Geevarghese, BA;
Samantha R. Goldburg, BA; Saadat A. Khan, MD; Massimiliano Szulc, PhD;
Mark B. Ratcliffe, MD; Robert A. Levine, MD; Ashley E. Morgan, MD; Pooja Maddula;
Meenakshi Rozenstrauch, MS; Tara Shah, MD; Richard B. Devereux, MD;
Jonathan W. Weinsaft, MD

BackgroundRight ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors,
Downloaded from http://circimaging.ahajournals.org/ by guest on December 12, 2016

including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between
LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown.
Methods and ResultsThe population comprised 2051 patients who underwent exercise stress myocardial perfusion
imaging and echo (5.57.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores
were 3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion
defects (all P0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both
P<0.01), without difference in corresponding anterior defects (P=0.13). In multivariable analysis, inducible inferior and
lateral wall perfusion defects increased the likelihood of RV dysfunction (both P<0.05) independent of LV function,
fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance
whether measured by exercise duration (6.72.8 versus 7.92.9 minutes; P<0.001) or peak treadmill stage (2.60.9 versus
3.11.0; P<0.001), paralleling results among patients with LV dysfunction (7.02.9 versus 8.02.9; P<0.001|2.71.0
versus 3.11.0; P<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction
(P<0.001) and was associated with each parameter independent of age or medication regimen.
ConclusionsAmong patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior
and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent
of LV dysfunction.(Circ Cardiovasc Imaging. 2016;9:e005115. DOI: 10.1161/CIRCIMAGING.116.005115.)

Key Words:echocardiography exercise exercise test exercise tolerance heart failure

R ight ventricular (RV) systolic dysfunction is an adverse

prognostic marker that has been shown to confer
increased risk for heart failure and death.13 RV and left ven-
tricular (LV) performance are closely linked due to a variety
of factors, including common coronary arterial blood sup-
ply. Patients with LV injury have been shown to develop RV
dysfunction in the extreme case of myocardial infarction, for
which risk for RV dysfunction varies in relation to LV infarct
pattern.2,4 By extension, LV ischemia holds the potential to
impact RV performance, due to both direct (ie, altered RV per-
fusion) and indirect (ie, increased RV afterload) mechanisms.
However, magnitude and distribution of LV ischemia have yet
to be studied as markers of RV dysfunction.
See Editorial by Miller and Anavekar
See Clinical Perspective
Radionuclide stress myocardial perfusion imaging (MPI)
is widely used to assess LV ischemic burden, as supported
by data showing extent and severity of perfusion deficits to
correspond with anatomic burden of atherosclerotic plaque
and predict adverse prognosis.5,6 MPI is often performed
adjunctively with exercise treadmill testing, enabling perfu-
sion data to be acquired together with physiological exercise
parameters that are known to predict adverse prognosis.710
Paralleling uncertainty regarding perfusion-based markers of
RV dysfunction, the independent impact of RV performance

Received May 21, 2016; accepted September 19, 2016.

From the Greenberg Cardiology Division, Department of Medicine (J.K., T.S., A.S., P.N.K., A.G., S.R.G., S.A.K., M.S., P.M., M.R., T.S., R.B.D.,
J.W.W.) and Department of Cardiothoracic Surgery (A.D.F.), Weill Cornell Medical College, New York, NY; Division of Cardiology, Department of
Surgery (M.B.R., A.E.M.), and Department of Bioengineering (M.B.R., A.E.M.), University of California, San Francisco; Veterans Affairs Medical Center,
San Francisco, CA (M.B.R., A.E.M.); and Massachusetts General Hospital, Harvard Medical School, Boston (R.A.L.).
Correspondence to Jonathan W. Weinsaft, MD, Nuclear Cardiology, Cardiac MRI Programs, Weill Cornell Medical College, 525 E 68th St, New York,
NY 10021. E-mail jww2001@med.cornell.edu
2016 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org DOI: 10.1161/CIRCIMAGING.116.005115

1
 2 Kim et al RV Dysfunction and Exercise Stress Perfusion
on exercise tolerance is unknown. Given that nearly half of
all patients with symptomatic heart failure have preserved
LV systolic function,11 identification of novel parameters
that impact effort toleranceas offered by readily assess-
able indices of RV functionis of widespread clinical
significance.
This study assessed RV functionas well as clinical,
exercise, and myocardial perfusion indicesamong a broad
cohort undergoing echocardiography and exercise MPI so as
to test the primary hypothesis that RV dysfunction impairs
exercise tolerance independent of LV contractile function. To
do so, multimodality imaging was used, whereby MPI was
used as the reference for LV perfusion pattern and echo as
the reference for RV (and LV) structure/function. Study goals
were 3-fold: (1) to assess prevalence and clinical markers of
RV dysfunction among patients with known or suspected cor-
onary artery disease (CAD) undergoing exercise stress testing,
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(2) to determine whether pattern and severity of LV perfusion
deficits modifies risk for RV dysfunction, and (3) to test the
impact of RV dysfunction on exercise tolerance.
Methods
Population
The population comprised consecutive patients who underwent
clinically indicated transthoracic echocardiography (echo) within
1 month of exercise single-photon emission computed tomography
(SPECT) MPI: A maximum interval of 1 month was selected so
as to minimize the impact of changes in loading conditions on RV
performance during the interval between tests. Imaging was per-
formed February 2011 to January 2016 at Weill Cornell Medical
College. To ensure accurate echo categorization of RV perfor-
mance, both tricuspid annular plane systolic excursion (TAPSE)
and peak tricuspid annular systolic velocity (S) were required for
study inclusion: 7% (n=166) of otherwise eligible patients were ex-
cluded due to absence of TAPSE or S. No patients were excluded
based on clinical characteristics or MPI results. This retrospec-
tive protocol was approved by the Weill Cornell Medical College
Institutional Review Board.
Imaging Protocol
Single-Photon Emission Computed Tomography
MPI was performed in accordance with a previously described pro-
tocol using a dual headed scintillation camera system with a low-en-
ergy high-resolution collimator.12,13 In brief, thallium-201 (3 mCi)
or technetium-99m sestamibi (10 mCi) was injected intravenously;
baseline (ie, rest) perfusion images were acquired 10 minutes after
Tl-201 and 60 minutes after Tc-99m sestamibi injection. Symptom
limited exercise treadmill testing was performed using a Bruce pro-
tocol: Tc-99m (30 mCi) was intravenously administered at peak
stress, for which a minimum target heart rate response to exercise
(85% predicted maximum heart rate [220-age]) was used as the
criterion for adequate workload required for radionuclide injec-
tion.14 Serial 12-lead ECGs and blood pressure measurements were
obtained (together with assessment of clinical symptoms) at base-
line and at each stage of the exercise treadmill protocol. For patients
unable to attain target heart rate during exercise, pharmacological
(adenosine or regadenoson) stress was performed after treadmill
testingpatients were instructed to refrain from caffeine intake >12
hours before MPI. Either attenuation correction imaging or prone
reposition imaging or both, as clinically tolerated, was used to dif-
ferentiate between pathological perfusion deficits and attenuation
artifact in accordance with previously used methods.12,15 Poststress
images were acquired 30 minutes after exercise and 1 to 2 hours
after pharmacological stress.
Echocardiography
Noncontrast transthoracic echoes were performed by experienced
sonographers using commercially available equipment. Images were
acquired in standard parasternal and apical 2-, 3-, and 4-chamber
orientations. RV systolic function assessment was performed using
M-mode (for TAPSE) and tissue Doppler (for S) imaging. In accor-
dance with consensus standards, TAPSE and S data were acquired in
apical 4-chamber orientation.16
Image Analysis
Single-Photon Emission Computed Tomography
MPI was interpreted by the American Heart Association/American
College of Cardiology level IIItrained readers, for whom high re-
producibility has been previously reported.17 Visual interpretation was
confirmed by review of polar plots with comparison of segmental radio-
tracer intensity to computer-generated, sex-matched data sets. Perfusion
defect severity on a per-segment basis was graded using a standard 17
segment, 5-point per-segment scoring system (0=normal, 1=equivocal
or mildly reduced, 2=moderately reduced, 3=severely reduced, and
4=absence of detectable radioisotope uptake).18 Fixed segments were
defined as those with matched perfusion abnormalities (matched scores)
on stress and rest; ischemic segments were defined as those with in-
ducible abnormalities (stress>rest). Summed stress and rest scores
were calculated by adding per-segment defect severity for all segments.
Inducible perfusion abnormalities (summed difference score) were as-
sessed as the difference between rest and stress images. MPI exams
were interpreted blinded to echo-based quantification of RV function.
Regional LV perfusion was assessed using uniform partitions
(Figure1), whereby LV was partitioned into 3 equal size (anterior, infe-
rior, and lateral) territories, in accordance with previous methods as used
by our group15,19: summed stress, rest, and difference scores in each ter-
ritory were calculated as the sum of individual perfusion scores within
encompassed segments. Perfusion territories were not mutually exclu-
sive; patients with defects in multiple territories were scored for each
territory based on extent and severity of constitutive segmental deficits.
Perfusion Territories
Anterior
1. Basal anterior
2. Basal anteroseptal
3. Basal inferoseptal
4. Basal inferior
5. Basal inferolateral
6. Basal anterolateral
Inferior
7. Mid anterior
8. Mid anteroseptal
9. Mid inferoseptal
10. Mid inferior
11. Mid inferolateral
12. Mid anterolateral
13. Apical anterior
Lateral 14. Apical septal
15. Apical inferior
16. Apical lateral
17. Apex
Figure 1. LV perfusion territories. Bullseye plots illustrating
regional left ventricular (LV) perfusion territories (highlighted).
Each category comprised 5 segments, such that the total myo-
cardium subtended by each was equivalent.
 3 Kim et al RV Dysfunction and Exercise Stress Perfusion
Echocardiography
Echoes were interpreted by experienced investigators within a high-
volume laboratory, for which expertise and reproducibility for quan-
titative LV and RV indices have been documented.20,21 RV systolic
function was visually scored and quantified via TAPSE and S, which
were acquired in accordance with consensus guidelines: TAPSE was
measured (on M-mode) as the distance of systolic excursion of the
lateral tricuspid annulus along its longitudinal plane. S was measured
(on tissue Doppler) as the peak tricuspid annular longitudinal veloc-
ity of excursion. Established cutoffs (TAPSE <1.6 cm, S< 10 mm/s)
were used for each parameter16; cutoffs were defined prospectively
for data analysis purposes. To reduce false-positive classification, RV
dysfunction was defined by impairment of both TAPSE and S.
Additional analyses were performed to assess RV remodeling and
ancillary indices relevant to effort tolerance. RV size was measured
as the basal linear end-diastolic diameter in a 4-chamber orientation.22
Pulmonary artery systolic pressure was calculated based on tricus-
pid regurgitant velocity and inferior vena cava caliber. LV systolic
function, geometry, and mass were quantified based on linear dimen-
sions in parasternal long axis, consistent with quantitative methods
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previously validated in necropsy-comparison and population-based
outcomes studies.2327 Mitral regurgitation was graded in accordance
with consensus guidelines28; severity was categorized using a 5-point
(04+) scale based on aggregate data yielded by vena contracta,
volumetric indices, jet depth, and mitral and pulmonary vein flow
pattern.15,29
Statistical Methods
Comparisons between groups with or without RV dysfunction were
made using the Student t test (expressed as meanSD) for continu-
ous variables. Categorical variables were compared using 2 tests or
when <5 expected outcomes per cell, the Fisher exact test was used.
Multiple group comparisons were performed using 2-way ANOVA;
ranked variables (ie, global perfusion scores) were compared using
the KruskalWallis test. Multivariable logistic regression analysis
was used to test whether LV perfusion deficit pattern was indepen-
dently associated with RV dysfunction after controlling for mag-
nitude of LV systolic dysfunction and RV afterload (ie, pulmonary
artery pressure); variables were concomitantly entered into the mul-
tivariable model after each were confirmed to be associated with RV
dysfunction in univariable analysis. Linear regression was used to test
variables associated with exercise time. Statistical calculations were
performed using SPSS 22.0 (SPSS, Inc, Chicago, IL). Two-sided
P<0.05 was considered indicative of statistical significance.
Results
Population Characteristics
The study population comprised 2051 patients who under-
went echo and MPI within 1 month (mean: 5.57.9 days [73%
within 7 days]) reflecting 15.9% (2051/12841) of all patients
who underwent MPI during study period. Among the study
population, 6.0% (n=123) had echo-evidenced RV dysfunc-
tion as manifested by both impaired TAPSE and RV S.
Table1 details population characteristics stratified by RV
functional status, including clinical conditions and patient-
reported baseline medications at the time of MPI. As shown,
diabetes mellitus and hypertension were more common among
patients with RV dysfunction (P<0.05), paralleling increased
prevalence of clinically reported obstructive CAD at time
of stress testing (P<0.001). Consistent with the concept that
adverse LV remodeling impacts RV performance, both MPI
and echo demonstrated that LV systolic function was lower,
LV chamber size larger, and pulmonary artery pressure higher
among patients with RV dysfunction (all P<0.01). Of note,
Table1 also demonstrates that less than half (40%) of patients
with quantitative RV dysfunction as measured via TAPSE and
S were identified based on qualitative visual assessment alone.
Myocardial Perfusion Pattern
Table2 compares perfusion indices in relation to RV func-
tion, including its composite parameters of TAPSE and S.
As shown, global LV summed stress scores were on average
3-fold higher among patients with RV dysfunction, attrib-
utable to increments in inducible (summed difference score)
and fixed perfusion defects (all P0.001). Perfusion defect
severity was paralleled by increased defect size, as measured
based on greater number of segments with inducible and fixed
perfusion defects among patients with RV dysfunction (both
P<0.001). Regarding regionality, both inferior and lateral wall
ischemia was greater among patients with RV dysfunction
(both P0.01), whereas corresponding anterior wall defects
(whether measured based on summed difference score or num-
ber of ischemic segments) were similar (P0.13). Table2 also
demonstrates that perfusion defect findings associated with
the composite definition of RV dysfunction by both TAPSE
and S were similar with RV dysfunction defined by each of
the 2 individual parameters. Multivariable logistic regression
analysis (Table3) was used to test whether LV perfusion defi-
cit pattern was independently associated with RV dysfunction
after controlling for conventional factors.
As shown in Table 3, inducible myocardial perfusion
defects (as measured in the inferior or lateral walls) increased
the likelihood of RV dysfunction (both P<0.05). Of note,
modeling data demonstrated that the relationship between RV
dysfunction and LV perfusion deficits was continuous, such
that likelihood of RV dysfunction increased in relation to size
of LV perfusion deficit. Applied clinically, results indicate that
ischemic perfusion deficits involving 3 LV segments in the
inferior or lateral walls would be expected to more than double
the likelihood for RV dysfunction even after controlling for
magnitude of LV dysfunction and pulmonary hypertension.
RV Function in Relation to Effort Tolerance
All patients initiated a standardized Bruce exercise treadmill
protocol, for which a target of 85% predicted maximal heart
rate (220-age) was required for test completion. As shown
in Table 4, exercise-induced hemodynamic indices, includ-
ing change in heart rate and systolic blood pressure, were
lower among patients with RV dysfunction (both P<0.001):
results paralleled differences among patients with LV systolic
dysfunction defined by ejection fraction <50% (heart rate:
6027 versus 7024 bpm|blood pressure: 3331 versus
4227 mmHg; both P0.001). Patients with RV dysfunc-
tion also demonstrated lesser effort tolerance whether mea-
sured by exercise duration or peak Bruce stage achieved (both
P<0.001), again paralleling results among patients with LV
dysfunction (7.02.9 versus 8.02.9|2.71.0 versus 3.11.0;
both P<0.001). Accordingly, both groups were more likely
to require conversion of exercise testing to pharmacological
stress (RV dysfunction: 35% versus 19%; P<0.001|LV dys-
function: 27% versus 19%; P=0.03).
Figure2 stratifies exercise time in relation to RV and LV
systolic function. As shown, effort tolerance decreased in rela-
tion to both functional parameters, as evidenced by stepwise
 4 Kim et al RV Dysfunction and Exercise Stress Perfusion

Table 1. Population Characteristics

Overall (n=2051) RV Dysfunction (n=1928)* RV Dysfunction+ (n=123) P
Clinical
Age, y 6412 6312 6612 0.01
Male sex 1211 (59%) 1118 (58%) 93 (76%) <0.001
Body mass index, kg/m2 28.55.8 28.55.9 28.05.2 0.36
Atherosclerosis risk factors

Diabetes mellitus 528 (26%) 477 (25%) 51 (41%) <0.001

Hypertension 1311 (64%) 1221 (63%) 90 (73%) 0.03

Tobacco use 166 (8%) 161 (8%) 5 (4%) 0.09

Hypercholesterolemia 1339 (65%) 1252 (65%) 87 (71%) 0.19
Family history of coronary artery disease 636 (31%) 602 (31%) 34 (28%) 0.41
Known coronary artery disease 566 (28%) 489 (25%) 77 (63%) <0.001
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Previous myocardial infarction 215 (10%) 197 (10%) 18 (15%) 0.12

Previous coronary revascularization (PCI/CABG) 459 (22%) 389 (20%) 70 (57%) <0.001
Chronic obstructive pulmonary disease 84 (4%) 78 (4%) 6 (5%) 0.65
Pulmonary embolism (history) 27 (1%) 25 (1%) 2 (2%) 0.68
Sleep apnea 131 (6%) 129 (7%) 2 (2%) 0.02
Indication for stress testing

Chest pain 1169 (57%) 1113 (58%) 56 (46%) 0.008

Dyspnea 662 (32%) 622 (32%) 40 (33%) 0.95
Medication regimen

Aspirin 1089 (53%) 1003 (52%) 86 (70%) <0.001

Thienopyridines 239 (12%) 223 (12%) 16 (13%) 0.63
-Blocker
 809 (39%) 726 (38%) 83 (67%) <0.001
ACE inhibitor/angiotensin receptor blocker 830 (40%) 769 (40%) 61 (50%) 0.03
HMG-CoA reductase inhibitor 1092 (53%) 1003 (52%) 89 (72%) <0.001
Calcium channel blockers 419 (20%) 394 (20%) 25 (20%) 0.98

Nitrates 72 (4%) 65 (3%) 7 (6%) 0.18
Electrocardiography
Sinus rhythm 1987 (97%) 1880 (98%) 107 (87%) <0.001
Atrial fibrillation or flutter 45 (2%) 34 (2%) 11(9%) <0.001
Q-wave myocardial infarction

Anterior 31 (2%) 29 (2%) 2 (2%) 0.71

Lateral 12 (1%) 11 (1%) 1 (1%) 0.53

Inferior 46 (2%) 37 (2%) 9 (7%) <0.001
Imaging
Right ventricular function/morphology

Echocardiography

TAPSE 2.10.4 2.20.4 1.30.2 <0.001

RV S 12.52.5 12.82.3 8.01.2 <0.001
RV end-diastolic diameter, cm/m 2
1.70.3 1.70.3 1.80.4 0.31

Qualitative RV dilation 85 (4%) 62 (3%) 23 (19%) <0.001

Qualitative RV dysfunction 70 (3%) 21 (1%) 49 (40%) <0.001
Left ventricular function/morphology
(Continued)
 5 Kim et al RV Dysfunction and Exercise Stress Perfusion

Table 1. Continued
Overall (n=2051) RV Dysfunction (n=1928)* RV Dysfunction+ (n=123) P

SPECT
Poststress ejection fraction, % 6411 6410 5613 <0.001
LV end-diastolic volume, mL/m2 4817 4816 5523 <0.001

Echocardiography
Ejection fraction, %
 629 629 5314 <0.001
Advanced LV dysfunction (EF <35%) 2.60.3 2.60.3 2.70.4 0.12
LV end-diastolic diameter, cm/m 2
1.70.3 1.70.3 1.90.4 <0.001
LV end-systolic diameter, cm/m 2
8524 8524 9025 0.04
LV mass, g/m
 2
629 629 5314 <0.001
Left atrial size, cm2/m2 9.82.3 9.82.2 11.13.1 <0.001
Left atrial diameter, cm/m 2
2.00.3 2.00.3 2.20.4 <0.001
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Mitral regurgitation (moderate) 64 (3%) 55 (3%) 9 (7%) 0.01

Tricuspid regurgitation (moderate) 64 (3%) 54 (3%) 10 (8%) 0.001
PASP 318 307 3412 0.008
Pulmonary hypertension (PASP 35 mmHg) 377 (22%) 341 (21%) 36 (32%) 0.006
ACE indicates angiotensin-converting enzyme; CABG, coronary artery bypass grafting; EF, ejection fraction; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; LV,
left ventricular; PASP, pulmonary artery systolic pressure; PCI, percutaneous coronary intervention; RV, right ventricular; SPECT, single-photon emission computerized
tomography; and TAPSE, tricuspid annular plane systolic excursion.
*Defined based on established cutoffs as used in consensus guidelines (TAPSE <1.6 cm; S <10 mm/s).16
Indicates P values <0.05.
Available in 83% of study population (n=1711).

decrements in patients with normal biventricular function com-
pared with those with isolated ventricular dysfunction, and
biventricular dysfunction. Of note, effort tolerance was >1 min-
ute lower among patients with isolated RV dysfunction as com-
pared with those with normal biventricular function (6.92.6
versus 8.12.9; P=0.001), paralleling similarly lower exercise
duration among patients with isolated LV dysfunction com-
pared with normal controls (7.12.9 versus 8.12.9; P<0.001).
RV and LV dysfunction were each associated with impaired
exercise time in univariable linear regression (P<0.001): in
multivariable analysis, impaired effort tolerance (assessed per
minute exercise time) was independently associated with RV
dysfunction (regression coefficient 0.73 [95% confidence inter-
val, 0.141.31]; P=0.02) and LV dysfunction (regression coef-
ficient, 0.71 [95% confidence interval, 0.271.16]; P=0.002),
even after controlling for age (regression coefficient, 0.66 per
decade [95% confidence interval, 0.550.77]; P<0.001) and
-blocker use (regression coefficient, 0.66 [95% confidence
interval, 0.390.93]; P<0.001) at time of stress testing.
Discussion
This studyperformed among a broad cohort of patients under-
going stress MPI and echoprovides new insights concerning
links between LV ischemia and RV performance, as well as
the independent impact of RV dysfunction on effort tolerance.
There are several key findings: first, although RV dysfunction
was uncommon (6%) among the overall cohort of patients
undergoing MPI, prevalence was higher among patients with
CAD risk factors and markedly increased (63%) among those
with known CAD (P<0.001). Second, regional LV perfusion
impacted likelihood of RV dysfunction, as evidenced by the
fact that both inferior and lateral wall ischemia was greater
among patients with RV dysfunction (both P0.01), whereas
corresponding anterior wall deficits (whether measured based
on summed difference score or number of ischemic segments)
were similar. In multivariable analysis, inducible perfusion
defects in the LV inferior or lateral walls were independently
associated with RV dysfunction even after controlling for
magnitude of LV dysfunction, fixed defects, and pulmonary
artery systolic pressure. Finally, multiple physiological indi-
ces of effort tolerance (eg, heart rate, blood pressure, effort
time) were impaired among patients with RV dysfunction (all
P<0.001), paralleling results among patients with LV dysfunc-
tion: exercise time decreased stepwise in relation to both RV
and LV dysfunction (P<0.001) and was associated with each
parameter independent of age or medication regimen.
To the best of our knowledge, this is the first study to
demonstrate a link between LV ischemia and RV function.
Our observed association between inferior and lateral wall
inducible perfusion defects and RV dysfunction is consistent
with established concepts regarding LV perfusion pattern
and RV blood flow. Previous studies have shown inferior and
lateral wall perfusion deficits on MPI to correspond to occlu-
sion of the right coronary and left circumflex arteries,30 each
of which would be expected to variably provide blood flow
to the RV based on coronary dominance pattern. Of note,
anterior ischemia was not associated with RV dysfunction
despite the fact that the left anterior descending artery often
provides blood flow to the RV apex. One possible explana-
tion for this concerns the measurement technique used to
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Table 2. Myocardial Perfusion Pattern

Normal
Normal RV Function* Impaired RV Function Normal TAPSE Abnormal TAPSE RV S Abnormal RV S
(n=1928) (123) P (1886) (165) P (1767) (284) P
Global LV perfusion
Summed stress
2.76.1 6.98.5 <0.001 2.66.0 6.58.5 <0.001 2.55.8 5.68.5 <0.001
score
(03|48 1528 (79%)|179 (9%)| 60 (49%)|23 (19%)| 1502(80%)|172(9%)| 86(52%)|30(18%)| 1420(80%)|155(9%)| 168(59%)|47(17%)|
<0.001 <0.001 <0.001
|913|>13) 88 (5%)|133 (7%) 14 (11%)|26 (21%) 85(5%)|127(7%) 17(10%)|32(19%) 79(5%)|113(6%) 23(8%)|46(16%)
Summed rest score 1.95.0 4.46.7 <0.001 1.84.9 4.47.1 <0.001 1.74.7 3.97.2 <0.001
(03|48 1620 (84%)|160 (8%)| 75 (61%)|22 (18%)| 1592 (84%)|155 (8%)| 103(62%)|27 (16%)| 1501 (85%)|139 (8%)| 194(68%)|43 (15%)|
<0.001 <0.001 <0.001
|913|>13) 71 (4%)|77 (4%) 15 (12%)|11 (9%) 65(3%)|74 (4%) 21 (13%)|14 (9%) 65 (4%)|62 (4%) 21 (7%)|26 (9%)
Summed difference
0.82.7 2.55.3 0.001 0.82.7 2.14.8 0.001 0.82.7 1.84.2 <0.001
score
(0|15|610|>10) 1629(85%)|204(11%) 79(64%)|24(20%)| 1595(85%)|198(11%)| 113(69%)|30(18%)| 1510(86%)|172(10%)| 198(70%)|56(20%)|
<0.001 <0.001 <0.001
|63(3%)|32(2%) 13(11%)|7(6%) 61(3%)|32(2%) 15(9%)|7(4%) 56(3%)|29(2%) 20 (7%)|10(4%)
Number of ischemic
0.61.6 1.62.8 <0.001 0.51.6 1.32.6 <0.001 0.51.6 1.22.3 <0.001
segments
Number of fixed
0.71.8 1.72.5 <0.001 0.71.8 1.72.7 <0.001 0.71.2 1.52.6 <0.001
segments
Normal perfusion 1393 (72%) 50 (41%) <0.001 1370 (73%) 72 (44%) <0.001 1298 (74%) 145 (51%) <0.001
Fully reversible defects 113 (6%) 12 (10%) 0.08 110 (6%) 15 (9%) 0.09 99 (6%) 26 (9%) 0.02
6 Kim et al RV Dysfunction and Exercise Stress Perfusion

Partially reversible
236 (12%) 29 (24%) <0.001 225 (12%) 40 (24%) <0.001 212(12%) 53 (19%) 0.002
defects
Fixed defects 186 (10%) 32 (26%) <0.001 181 (10%) 37 (22%) <0.001 158 (9%) 50 (21%) <0.001
Regional perfusion
Perfusion defect severity
Anterior

Summed stress
0.62.1 1.32.9 0.01 0.62.1 1.12.7 0.02 0.52.0 1.23.0 0.001
score

Summed rest
0.31.6 0.82.5 0.03 0.31.6 0.72.3 0.02 0.31.4 0.82.7 0.003
score

Summed
0.31.2 0.51.4 0.14 0.31.2 0.41.2 0.39 0.31.2 0.41.2 0.06
difference score

Number of
ischemic 0.20.7 0.30.8 0.13 0.20.7 0.20.7 0.42 0.20.7 0.30.8 0.02
segments
(Continued)
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Table 2. Continued
Normal
Normal RV Function* Impaired RV Function Normal TAPSE Abnormal TAPSE RV S Abnormal RV S
(n=1928) (123) P (1886) (165) P (1767) (284) P
Number of fixed
0.10.6 0.41.0 0.009 0.10.6 0.30.9 0.003 0.10.6 0.30.9 0.002
segments
Inferior

Summed stress
1.22.9 3.03.9 <0.001 1.22.9 2.94.0 <0.001 1.22.9 2.43.6 <0.001
score

Summed rest
1.02.6 2.33.6 <0.001 1.02.6 2.33.7 <0.001 0.92.6 1.93.4 <0.001
score

Summed
0.21.0 0.71.7 0.007 0.21.0 0.61.5 0.008 0.21.0 0.41.4 0.009
difference score

Number of
ischemic 0.20.7 0.41.0 0.005 0.20.7 0.40.9 0.006 0.20.7 0.30.8 0.006
segments
Number of fixed
0.41.0 0.91.4 <0.001 0.41.0 0.91.4 <0.001 0.41.0 0.81.3 <0.001
segments
Lateral

Summed stress
0.52.0 2.03.3 <0.001 0.52.0 1.83.4 <0.001 0.41.9 1.43.1 <0.001
score

Summed rest
0.31.6 0.71.9 0.008 0.31.5 0.82.3 0.005 0.21.5 0.62.1 0.004
7 Kim et al RV Dysfunction and Exercise Stress Perfusion

score

Summed
0.21.1 1.22.6 <0.001 0.21.1 1.02.4 <0.001 0.21.1 0.82.1 <0.001
difference score

Number of
ischemic 0.10.6 0.81.5 <0.001 0.10.6 0.61.4 <0.001 0.10.6 0.51.2 <0.001
segments
Number of fixed
0.10.5 0.20.7 0.01 0.10.4 0.30.8 0.004 0.10.4 0.20.7 0.004
segments
RV indicates right ventricular; S, peak tricuspid annular systolic velocity; and TAPSE, tricuspid annular plane systolic excursion.
*Defined as both normal TAPSE and S, via established cutoffs as used in consensus guidelines (TAPSE 1.6 cm, S 10 mm/s).16
Defined as both abnormal TAPSE and S (TAPSE <1.6 cm, S <10 mm/s).
Indicates P values <0.05.
 8 Kim et al RV Dysfunction and Exercise Stress Perfusion

Table 3. Perfusion-Based Correlates of Right Ventricular Systolic Dysfunction

Model 2 =93.96, P<0.001
Univariable Multivariable
Variable Odds Ratio 95% Confidence Interval P Odds Ratio 95% Confidence Interval P
Inferior/lateral ischemic perfusion defect
1.40 1.291.56 <0.001 1.39 1.241.57 <0.001
size* (number of segments)
Inferior/lateral fixed perfusion defect size*
1.31 1.191.45 <0.001 1.15 0.991.32 0.06
(number of segments)
LV ejection fraction (per 10-point decrement) 1.71 1.541.88 <0.001 1.62 1.411.83 <0.001
Pulmonary arterial systolic pressure (per 10
1.44 1.221.67 <0.001 1.19 0.931.46 0.16
mmHg)
*Inferior/lateral defect size was calculated by summing aggregate number of affected segments in these territories.
Indicates P values <0.05.

assess RV function: whereas TAPSE and S are included in ischemia itself bears minimal consequences for RV function,
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consensus echo guidelines as well-validated indices for RV
function,16 both are measures of tricuspid annular/basal RV
excursion and would not necessarily be impacted by regional
dysfunction of the RV apex. Concerning our observation
that anterior fixed defects were larger among patients with
RV dysfunction, it is possible that the distal RV (as may be
supplied by the left anterior descending artery) contributes
relatively little to global RV performance, such that anterior
but that anterior infarction produces adverse LV remodel-
ing that bears secondary consequences on RV performance.
Consistent with this, several previous studies have shown
RV dysfunction (measured via echocardiography, radionu-
clide cine-angiography, or cardiac magnetic resonance) to be
less common among patients with anterior MI2,4 but pres-
ent in 17% to 40% of such cases.2,4,31 Taken together, these
data suggest that our findings are consistent with previous

Table 4. Exercise Physiological Parameters in Relation to RV Function

Overall (n=2051) RV Dysfunction (n=1928) RV Dysfunction+ (n=123) P
Effort tolerance
Exercise duration (time) 7.82.9 7.92.9 6.72.8 <0.001
Peak treadmill stage achieved 2.60.96 2.60.96 2.20.91 <0.001
Workload (METS) 9.42.1 9.52.1 8.52.3 <0.001
Heart rate
Rest 70.412.3 70.312.2 72.113.3 0.15
Peak stress 138.425.2 139.125.0 128.326.9 <0.001
Change in heart rate (stressrest) 68.024.4 68.824.1 56.226.4 <0.001
Predicted maximum heart rate 156.511.7 156.711.7 154.011.5 0.014
% Converted to pharmacological stress testing* 415 (20%) 372 (19%) 43 (35%) <0.001
Systolic blood pressure
Rest 126.417.0 126.316.9 127.718.0 0.40
Peak stress 166.629.2 167.328.4 155.532.3 0.001
Change in blood pressure (stressrest) 40.227.7 41.027.3 27.931.0 <0.001
Exercise ECG response
1 mm ST depression, %
 389 (19%) 371 (19%) 18 (15%) 0.21
Maximal ST depression, mm 0.320.75 0.330.74 0.300.84 0.67
Exercise clinical response
Chest pain 104 (5%) 94 (5%) 10 (8%) 0.11
Shortness of breath 273 (13%) 254 (13%) 19 (15%) 0.47
Duke treadmill score 4.95.5 5.05.4 4.26.5 0.13
ECG indicates electrocardiogram; METS, metabolic equivalents; and RV, right ventricular.
*Failure to attain target heart rate (220-age).
Indicates P values <0.05.
 9 Kim et al RV Dysfunction and Exercise Stress Perfusion
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Figure 2. Exercise time in relation to ventricular function.
Exercise time (during Bruce treadmill protocol) among groups
partitioned based on left ventricular (LV) and right ventricular
(RV) systolic function (LV dysfunction P=0.034; RV dysfunction
P=0.008; interaction P=0.38). As shown, exercise time decreased
in relation to extent of systolic dysfunction, as evidenced by
stepwise decrements between patients with normal biventricular
function, isolated LV or RV dysfunction, and those with biventric-
ular dysfunction. LVEF indicates left ventricular ejection fraction;
and TAPSE, tricuspid annular plane systolic excursion.
literature and not primarily attributable to measurement
techniques.
Our observed link between RV dysfunction and reduced
exercise supports the notion that RV dysfunction alone can
impede effort tolerancea physiological parameter widely
used to stratify prognosis that has been shown to predict
cardiovascular and overall mortality in previous studies.710
Among our cohort, effort tolerance was >1 minute lower
among patients with isolated RV dysfunction compared
with those with normal biventricular function, paralleling
similar magnitude of difference when patients with isolated
LV dysfunction were compared with normal controls (both
P0.001). Our data among patients with known or suspected
CAD extends on previous studies in smaller cohorts, which
have suggested an association between RV dysfunction and
exercise capacity but have not directly tested whether RV
dysfunction provides incremental stratification above that
yielded by LV function alone. For example, among a cohort
of 23 healthy adolescents undergoing cardiopulmonary exer-
cise testing, Pieles et al32 reported that both RV and LV strain
increased in relation to work rate (P<0.05). Moreover, among
44 chronic obstructive pulmonary disease patients, Caminiti
et al33 reported that those with RV dysfunction (as defined
via TAPSE) had lower effort tolerance on baseline 6-minute
walk test (P=0.02) and lesser improvement after cardiopul-
monary rehabilitation (P<0.001). Other studies conducted
among patients with LV systolic dysfunction have linked
reduced right ventricular ejection fraction to impaired exercise
capacity as measured via peak oxygen consumption (V02 max)
during bicycle ergometry or treadmill exercise.3436 About
mechanism, it is possible that impaired RV function results
in decreased LV preload, thereby altering LV pressurevol-
ume filling curves and impeding LV contractile mechanics. It
is also possible that abnormal RV function (as measured by
TAPSE or S) is a marker for subtle changes in LV systolic
function not captured by widely used indices such as left
ventricular ejection fraction, such that LV contractile func-
tion is the primary determinant of effort tolerance and RV
dysfunction a secondary marker. Regardless of mechanism,
our data indicate RV dysfunction confers increased likeli-
hood for impaired exercise capacity, adding to a growing
body of literature demonstrating the importance of RV func-
tion as a marker of effort tolerance.13,3436
Several limitations should be noted. First, it is important
to recognize that SPECT does not assess absolute quantitative
blood flow and that this modality does not provide sufficient
spatial resolution to assess RV perfusion. On the contrary,
SPECT is widely used to assess ischemic burden, enabling
us to study a broad population-based cohort using a perfusion
approach that is well validated for prognostic risk stratifica-
tion.5 Second, our study assessed RV performance based on
TAPSE and S and used established binary cutoffs rather than
examining magnitude of dysfunction based on volumetric
right ventricular ejection fraction. Although TAPSE and S are
included in consensus guidelines16 and can be readily applied
in clinical practice and research, these methods extrapolate
global function based on tricuspid annular regional excur-
sions, potentially excluding the effect of RV apical dysfunc-
tion. Therefore, volumetric assessment using 3-dimensional
echo or cardiac magnetic resonance may have yielded differ-
ing results given its superior ability to detect RV dysfunction
as compared to 2-dimensional imaging alone.3,37 On the con-
trary, TAPSE and S have been shown to correlate with volu-
metric RV function20 and offer a means of RV assessment for
patients in whom 3-dimensional methods (eg, cardiac mag-
netic resonance) are contraindicated or unavailable, providing
a rationale for our imaging approach. An additional limita-
tion concerns the fact that chest pain history was assessed via
patient questionnaire at time of exercise MPI (for which avail-
able data were insufficient to classify chest pain features) and
that exercise treadmill data did not include postexercise vari-
ables such as heart rate recovery. It is also important to note
that SPECT assessment of ischemia burden was performed via
standardized scoring of perfusion defect severity and did not
include ancillary indices such as lungheart ratio. Finally, due
to large number of statistical tests used, type I error maybe
inflated using the prespecified P value cutoff (<0.05) as the
significance threshold per test.
Our results bear several key implications for clinical
practice and translational research. First, our finding of
an independent association between RV dysfunction and
decreased exercise treadmill time supports the notion that RV
performance should be evaluated as part of diagnostic testing
among patients with impaired effort capacity or associated
symptoms. Second, our results add to growing literature sup-
porting use of quantitative RV assessment for stratification
of physiological outcomes and demonstrate that simple RV
visual assessment (an approach widely used in current clini-
cal practice) can be limitedas evidenced by the fact that
less than half (40%) of patients in our cohort with quanti-
tative RV dysfunction were identified qualitatively. Finally,
given our demonstration of links between LV inferior/lateral
 10 Kim et al RV Dysfunction and Exercise Stress Perfusion
ischemia and RV dysfunction, future multicenter studies are
warranted to further confirm our findings and test whether
targeted coronary revascularization in these regions can be
used as a therapeutic means of augmenting RV contractility
and clinical performance status among patients with CAD.
Sources of Funding
This study was supported by a grant 1R01HL128278-01 (to J.W.
Weinsaft).
Disclosures
None.
References
1. Anavekar NS, Skali H, Bourgoun M, Ghali JK, Kober L, Maggioni AP,
McMurray JJ, Velazquez E, Califf R, Pfeffer MA, Solomon SD. Usefulness
of right ventricular fractional area change to predict death, heart failure, and
Downloaded from http://circimaging.ahajournals.org/ by guest on December 12, 2016
stroke following myocardial infarction (from the VALIANT ECHO Study).
Am J Cardiol. 2008;101:607612. doi: 10.1016/j.amjcard.2007.09.115.
2. Zornoff LA, Skali H, Pfeffer MA, St John Sutton M, Rouleau JL, Lamas GA,
Plappert T, Rouleau JR, Moy LA, Lewis SJ, Braunwald E, Solomon SD;
SAVE Investigators. Right ventricular dysfunction and risk of heart failure and
mortality after myocardial infarction. J Am Coll Cardiol. 2002;39:14501455.
3. Gulati A, Ismail TF, Jabbour A, Alpendurada F, Guha K, Ismail NA,
Raza S, Khwaja J, Brown TD, Morarji K, Liodakis E, Roughton M,
Wage R, Pakrashi TC, Sharma R, Carpenter JP, Cook SA, Cowie MR,
Assomull RG, Pennell DJ, Prasad SK. The prevalence and prognostic
significance of right ventricular systolic dysfunction in nonischemic di-
lated cardiomyopathy. Circulation. 2013;128:16231633. doi: 10.1161/
CIRCULATIONAHA.113.002518.
4. Pfisterer M, Emmenegger H, Mller-Brand J, Burkart F. Prevalence and
extent of right ventricular dysfunction after myocardial infarctionrela-
tion to location and extent of infarction and left ventricular function. Int J
Cardiol. 1990;28:325332.
5. Hachamovitch R, Berman DS, Shaw LJ, Kiat H, Cohen I, Cabico JA,
Friedman J, Diamond GA. Incremental prognostic value of myocardial
perfusion single photon emission computed tomography for the prediction
of cardiac death: differential stratification for risk of cardiac death and
myocardial infarction. Circulation. 1998;97:535543.
6. Lin F, Shaw LJ, Berman DS, Callister TQ, Weinsaft JW, Wong FJ, Szulc
M, Tandon V, Okin PM, Devereux RB, Min JK. Multidetector computed
tomography coronary artery plaque predictors of stress-induced myo-
cardial ischemia by SPECT. Atherosclerosis. 2008;197:700709. doi:
10.1016/j.atherosclerosis.2007.07.002.
7. Blair SN, Kohl HW 3rd, Paffenbarger RS Jr, Clark DG, Cooper KH,
Gibbons LW. Physical fitness and all-cause mortality. A prospective study
of healthy men and women. JAMA. 1989;262:23952401.
8. Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE.
Exercise capacity and mortality among men referred for exercise testing.
N Engl J Med. 2002;346:793801. doi: 10.1056/NEJMoa011858.
9. Roger VL, Jacobsen SJ, Pellikka PA, Miller TD, Bailey KR, Gersh BJ.
Prognostic value of treadmill exercise testing: a population-based study in
Olmsted County, Minnesota. Circulation. 1998;98:28362841.
10. Snader CE, Marwick TH, Pashkow FJ, Harvey SA, Thomas JD, Lauer
MS. Importance of estimated functional capacity as a predictor of all-
cause mortality among patients referred for exercise thallium single-pho-
ton emission computed tomography: report of 3,400 patients from a single
center. J Am Coll Cardiol. 1997;30:641648.
11. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM.
Trends in prevalence and outcome of heart failure with preserved ejection
fraction. N Engl J Med. 2006;355:251259. doi: 10.1056/NEJMoa052256.
12. Weinsaft JW, Gade CL, Wong FJ, Kim HW, Min JK, Manoushagian SJ,
Okin PM, Szulc M. Diagnostic impact of SPECT image display on assess-
ment of obstructive coronary artery disease. J Nucl Cardiol. 2007;14:659
668. doi: 10.1016/j.nuclcard.2007.06.115.
13. Weinsaft JW, Wong FJ, Walden J, Szulc M, Okin PM, Kligfield P.
Anatomic distribution of myocardial ischemia as a determinant of exer-
cise-induced ST-segment depression. Am J Cardiol. 2005;96:13561360.
doi: 10.1016/j.amjcard.2005.07.038.
14. Henzlova MJ, Duvall WL, Einstein AJ, Travin MI, Verberne HJ. Erratum
to: ASNC imaging guidelines for SPECT nuclear cardiology procedures:
stress, protocols, and tracers. J Nucl Cardiol. 2016;23:640642. doi:
10.1007/s12350-016-0463-x.
15. Volo SC, Kim J, Gurevich S, Petashnick M, Kampaktsis P, Feher A,
Szulc M, Wong FJ, Devereux RB, Okin PM, Girardi LN, Min JK, Levine
RA, Weinsaft JW. Effect of myocardial perfusion pattern on frequency
and severity of mitral regurgitation in patients with known or suspected
coronary artery disease. Am J Cardiol. 2014;114:355361. doi: 10.1016/j.
amjcard.2014.05.008.
16. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD,
Chandrasekaran K, Solomon SD, Louie EK, Schiller NB. Guidelines for
the echocardiographic assessment of the right heart in adults: a report from
the American Society of Echocardiography endorsed by the European
Association of Echocardiography, a registered branch of the European
Society of Cardiology, and the Canadian Society of Echocardiography.
JAm Soc Echocardiogr. 2010;23:685713; quiz 786688.
17. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK,
Pennell DJ, Rumberger JA, Ryan T, Verani MS; American Heart Association
Writing Group on Myocardial Segmentation and Registration for Cardiac
Imaging. Standardized myocardial segmentation and nomenclature for tomo-
graphic imaging of the heart. A statement for healthcare professionals from
the Cardiac Imaging Committee of the Council on Clinical Cardiology of the
American Heart Association. Int J Cardiovasc Imaging. 2002;18:539542.
18. Berman DS, Kiat H, Friedman JD, Wang FP, van Train K, Matzer L,
Maddahi J, Germano G. Separate acquisition rest thallium-201/stress
technetium-99m sestamibi dual-isotope myocardial perfusion single-pho-
ton emission computed tomography: a clinical validation study. J Am Coll
Cardiol. 1993;22:14551464.
19. Goyal P, Kim J, Feher A, Ma CL, Gurevich S, Veal DR, Szulc M, Wong FJ,
Ratcliffe MB, Levine RA, Devereux RB, Weinsaft JW. Myocardial perfu-
sion pattern for stratification of ischemic mitral regurgitation response to
percutaneous coronary intervention. Coron Artery Dis. 2015;26:642650.
doi: 10.1097/MCA.0000000000000271.
20. Kim J, Srinivasan A, Seoane T, Di Franco A, Peskin CS, McQueen DM,
Paul TK, Feher A, Geevarghese A, Rozenstrauch M, Devereux RB,
Weinsaft JW. Echocardiographic linear dimensions for assessment of
right ventricular chamber volume as demonstrated by cardiac magnetic
resonance. J Am Soc Echocardiogr. 2016;29:861870. doi: 10.1016/j.
echo.2016.05.002.
21. Palmieri V, Dahlf B, DeQuattro V, Sharpe N, Bella JN, de Simone G,
Paranicas M, Fishman D, Devereux RB. Reliability of echocardiographic
assessment of left ventricular structure and function: the PRESERVE
study. Prospective Randomized Study Evaluating Regression of
Ventricular Enlargement. J Am Coll Cardiol. 1999;34:16251632.
22. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L,
Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P,
Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang
W, Voigt JU. Recommendations for cardiac chamber quantification by
echocardiography in adults: an update from the American Society of
Echocardiography and the European Association of Cardiovascular
Imaging. J Am Soc Echocardiogr. 2015;28:139 e14.
23. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I,
Reichek N. Echocardiographic assessment of left ventricular hypertrophy:
comparison to necropsy findings. Am J Cardiol. 1986;57:450458.
24. Devereux RB, Reichek N. Echocardiographic determination of left ven-
tricular mass in man. Anatomic validation of the method. Circulation.
1977;55:613618.
25. Devereux RB, Roman MJ, Palmieri V, Liu JE, Lee ET, Best LG, Fabsitz
RR, Rodeheffer RJ, Howard BV. Prognostic implications of ejection frac-
tion from linear echocardiographic dimensions: the Strong Heart Study.
Am Heart J. 2003;146:527534. doi: 10.1016/S0002-8703(03)00229-1.
26. Palmieri V, Roman MJ, Bella JN, Liu JE, Best LG, Lee ET, Howard BV,
Devereux RB. Prognostic implications of relations of left ventricular sys-
tolic dysfunction with body composition and myocardial energy expendi-
ture: the Strong Heart Study. J Am Soc Echocardiogr. 2008;21:6671. doi:
10.1016/j.echo.2007.05.008.
27. Devereux RB, Wachtell K, Gerdts E, Boman K, Nieminen MS,
Papademetriou V, Rokkedal J, Harris K, Aurup P, Dahlf B. Prognostic
significance of left ventricular mass change during treatment of hyperten-
sion. JAMA. 2004;292:23502356. doi: 10.1001/jama.292.19.2350.
28. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine
RA, Nihoyannopoulos P, Otto CM, Quinones MA, Rakowski H, Stewart
WJ, Waggoner A, Weissman NJ; American Society of Echocardiography.
Recommendations for evaluation of the severity of native valvular regur-
gitation with two-dimensional and Doppler echocardiography. J Am Soc
Echocardiogr. 2003;16:777802. doi: 10.1016/S0894-7317(03)00335-3.
 11 Kim et al RV Dysfunction and Exercise Stress Perfusion

29. Jones EC, Devereux RB, Roman MJ, Liu JE, Fishman D, Lee ET, Welty
TK, Fabsitz RR, Howard BV. Prevalence and correlates of mitral regur-
gitation in a population-based sample (the Strong Heart Study). Am J
Cardiol. 2001;87:298304.
30. Pereztol-Valds O, Candell-Riera J, Santana-Boado C, Angel J, Aguad-
Bruix S, Castell-Conesa J, Garcia EV, Soler-Soler J. Correspondence be-
tween left ventricular 17 myocardial segments and coronary arteries. Eur
Heart J. 2005;26:26372643. doi: 10.1093/eurheartj/ehi496.
31. Larose E, Ganz P, Reynolds HG, Dorbala S, Di Carli MF, Brown KA, Kwong
RY. Right ventricular dysfunction assessed by cardiovascular magnetic reso-
nance imaging predicts poor prognosis late after myocardial infarction. J Am
Coll Cardiol. 2007;49:855862. doi: 10.1016/j.jacc.2006.10.056.
32. Pieles GE, Gowing L, Forsey J, Ramanujam P, Miller F, Stuart AG,
Williams CA. The relationship between biventricular myocardial per-
formance and metabolic parameters during incremental exercise and
recovery in healthy adolescents. Am J Physiol Heart Circ Physiol.
2015;309:H2067H2076. doi: 10.1152/ajpheart.00627.2015.
33. Caminiti G, Cardaci V, Conti V, DAntoni V, Murugesan J, Battaglia
D, Volterrani M. Right ventricular systolic dysfunction is related to
Downloaded from http://circimaging.ahajournals.org/ by guest on December 12, 2016
exercise intolerance in patients with chronic obstructive pulmonary
disease. J Cardiopulm Rehabil Prev. 2015;35:7074. doi: 10.1097/
HCR.0000000000000086.
34. de Groote P, Millaire A, Foucher-Hossein C, Nugue O, Marchandise X,
Ducloux G, Lablanche JM. Right ventricular ejection fraction is an inde-
pendent predictor of survival in patients with moderate heart failure. J Am
Coll Cardiol. 1998;32:948954.
35. Baker BJ, Wilen MM, Boyd CM, Dinh H, Franciosa JA. Relation of right
ventricular ejection fraction to exercise capacity in chronic left ventricular
failure. Am J Cardiol. 1984;54:596599.
36. Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventric-
ular ejection fraction predicts exercise capacity and survival in advanced
heart failure. J Am Coll Cardiol. 1995;25:11431153.
37. Kim J, Cohen SB, Atalay MK, Maslow AD, Poppas A. Quantitative as-
sessment of right ventricular volumes and ejection fraction in patients
with left ventricular systolic dysfunction by real time three-dimen-
sional echocardiography versus cardiac magnetic resonance imaging.
Echocardiography. 2015;32:805812. doi: 10.1111/echo.12715.

CLINICAL PERSPECTIVE
Right ventricular (RV) systolic dysfunction is a strong predictor of adverse clinical outcomes including heart failure and
death. The RV and left ventricle (LV) are closely linked due to a variety of mechanisms, including coronary blood supply that
commonly perfuses regions of the LV and RV. LV ischemia has the potential to affect RV contractile function both by direct
(ie, altered common blood supply) and indirect mechanisms (ie, increased RV afterload). In this study, 2051 patients under-
went exercise myocardial perfusion imaging and echocardiography within a narrow time intervalmyocardial perfusion
imaging was used to measure LV ischemia and echocardiography to assess RV function (via tricuspid annular plane systolic
excursion and peak tricuspid annular systolic velocity). Findings demonstrate global LV ischemic burden to be higher among
patients with RV dysfunction. Consistent with the concept that regional coronary perfusion has the potential to impact RV
performance, inferior and lateral ischemia were independently associated with RV dysfunction. Regarding exercise stress,
results demonstrate multiple indices of effort tolerance to be impaired among patients with RV dysfunction; exercise time
decreased stepwise in relation to both RV and LV dysfunction and was independently associated with each parameter.
These findings support the concept that RV performance impacts exercise tolerance and should be assessed in patients with
decreased effort tolerance or related heart failure symptoms. Given our demonstration of a link between regional LV isch-
emia and RV dysfunction, current findings lay the groundwork for future studies to test the concept of targeted coronary
revascularization as a therapeutic strategy for augmenting RV contractile function.
 Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular
Function Among Patients Undergoing Exercise Stress Myocardial Perfusion Imaging
Jiwon Kim, Antonino Di Franco, Tania Seoane, Aparna Srinivasan, Polydoros N. Kampaktsis,
Alexi Geevarghese, Samantha R. Goldburg, Saadat A. Khan, Massimiliano Szulc, Mark B.
Ratcliffe, Robert A. Levine, Ashley E. Morgan, Pooja Maddula, Meenakshi Rozenstrauch, Tara
Downloaded from http://circimaging.ahajournals.org/ by guest on December 12, 2016

Shah, Richard B. Devereux and Jonathan W. Weinsaft

Circ Cardiovasc Imaging. 2016;9:

doi: 10.1161/CIRCIMAGING.116.005115
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