Relation of the Prognostic Value of Ventilatory Efficiency to Body
Mass Index in Patients With Heart Failure
Paul Chase, MEd
a,
*, Ross Arena, PhD
b
, Jonathan Myers, PhD
d
, Joshua Abella MD
c
,
Mary Ann Peberdy, MD
c
, Marco Guazzi, MD, PhD
e
, and Daniel Bensimhon, MD
a
The ventilatory efficiency, minute ventilation (VE)/carbon dioxide production (VCO
2
),
slope consistently provides valuable prognostic information in patients with heart failure
(HF). Patients with a higher body mass index (BMI) have demonstrated an improved
prognosis in the HF population, a phenomenon that has been termed the “obesity para-
dox.” The purpose of this study was to evaluate the prognostic ability of the VE/VCO
2
slope
according to BMI in patients with HF. Seven-hundred four patients with HF (555 men, 149
women, mean age 56.8 13.4 years, ejection fraction 33.1 13.3%) with a BMI >18.5
kg/m
2
underwent cardiopulmonary exercise testing. Subjects were divided into 3 BMI
subgroups (18.5 to 24.9, 25.0 to 29.9, and >30 kg/m
2
). Each subject was tracked for major
cardiac events (death, transplantation, left ventricular assist device implantation) for 2
years after testing. There were 86 major cardiac events (71 deaths, 10 transplantations, 5
left ventricular assist device implantations) during the 2-year tracking period (overall
annual event rate 8.2%). The VE/VCO
2
slope was the strongest prognostic marker in each
BMI subgroup. Subjects in the highest BMI group had the lowest mean VE/VCO
2
slope and
the lowest rate of major cardiac events of the 3 groups. Multivariate Cox regression analysis
showed that peak VO
2
did not add additional prognostic value to the VE/VCO
2
slope and
was removed from the regression for each BMI subgroup. In conclusion, the findings of the
present study indicate that VE/VCO
2
slope maintains prognostic value irrespective of BMI
in patients with HF. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:
348 –352)
Obesity is associated with alterations in pulmonary function
and mechanics, leading to increased potential for obstruc-
tive sleep apnea, obesity/hypoventilation syndrome, dys-
pnea on exertion, and exercise intolerance. It has been well
established that the ventilatory efficiency, minute ventila-
tion (VE)/carbon dioxide production (VCO
2
), slope and
peak oxygen consumption (VO
2
) consistently provide valu-
able prognostic information in patients with heart failure
(HF).
1–6
Several recent studies have shown that the VE/
VCO
2
slope outperforms peak VO
2
in predicting major
cardiac events. To our knowledge, the effect of obesity on
the VE/VCO
2
slope and the prognostic power of cardiopul-
monary exercise testing in patients with HF have not been
fully evaluated. The purpose of this study was to evaluate
the prognostic ability of the VE/VCO
2
slope in patients with
HF across the spectrum of body mass index (BMI).
Methods
This study is a multicenter analysis including patients with
HF from cardiopulmonary exercise laboratories at San Pa-
olo Hospital (Milan, Italy), Virginia Commonwealth Uni-
versity (Richmond, Virginia), LeBauer Cardiovascular Re-
search Foundation (Greensboro, North Carolina), and the
VA Palo Alto Health Care System and Stanford University
(Palo Alto, California). A total of 704 patients with chronic
HF and tested between March 18, 1993 and March 5, 2007
were included. Inclusion criteria consisted of a diagnosis of
HF,
7
stable HF symptoms and medications for 1 month
before exercise testing, a BMI 18.5 kg/m
2
(lower thresh-
old of normal), and evidence of left ventricular systolic
and/or diastolic dysfunction by 2-dimensional echocardiog-
raphy performed within 1 month of exercise testing. Sub-
jects were classified as having systolic HF if they presented
with a left ventricular ejection fraction 45%. Subjects with
an ejection fraction 50% and clinical evidence of HF were
classified as having diastolic dysfunction.
8
As our group has
done previously,
3,4
patients with diastolic dysfunction (14%
of entire group) were grouped with subjects with nonisch-
emic HF for analysis. Subjects received routine follow-up
care at the 4 institutions included in this study. All subjects
completed a written informed consent and institutional re-
view board approval was obtained at each institution.
Symptom-limited cardiopulmonary exercise testing was
performed in all patients using treadmill
9
or cycle ergom-
etry
10
ramping protocols. A treadmill was used for testing in
American centers, whereas a lower extremity cycle ergome-
a
LeBauer Cardiovascular Research Foundation, Greensboro, North
Carolina;
b
Departments of Physical Therapy and
c
Internal Medicine, Vir-
ginia Commonwealth University, Richmond, Virginia;
d
VA Palo Alto
Health Care System, Cardiology Division, Stanford University, Palo Alto,
California; and
e
University of Milano, San Paolo Hospital, Cardiopulmo-
nary Laboratory, Cardiology Division, University of Milano, San Paolo
Hospital, Milano, Italy. Manuscript received June 16, 2007; revised manu-
script received and accepted August 24, 2007.
*Corresponding author: Tel: 336-832-2546; fax: 336-832-7746.
E-mail address: paul.chase@mosescone.com (P. Chase).
0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. www.AJConline.org
doi:10.1016/j.amjcard.2007.08.042