(Circulation. 1999;100:2411.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Ventilatory and Heart Rate Responses to Exercise
Better Predictors of Heart Failure Mortality Than Peak Oxygen Consumption
From the George M. and Linda Kaufman Center for Heart Failure, Desk F25, Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence and reprint requests to Michael S. Lauer, MD, FACC, Section of Heart Failure and Cardiac Transplantation Medicine, Department of Cardiology, Desk F25, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionConclusionsReferences |
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Background—An abnormally low chronotropic response and an abnormally high ventilatory response (
E/CO2) to exercise
are common in patients with severe heart failure, but their relative
prognostic impacts have not been well explored.
Methods and Results—Consecutive patients with heart failure
referred for metabolic stress testing who were not taking
ß-blockers or intravenous inotropes (n=470) were followed
for 1.5 years. The chronotropic index was calculated while peak
O2 and
E/CO2 were directly
measured. Chronotropic index and peak O2
were considered abnormal if in the lowest 25th percentiles of the
patient cohort, whereas
E/CO2 was considered
abnormal if in the highest 25th percentile. For comparative purposes, a
group of 17 healthy controls underwent metabolic testing as
well. Compared with controls, heart failure patients had markedly
abnormal ventilatory and chronotropic responses to exercise. In the
heart failure cohort, there were 71 deaths. In univariate
analyses, predictors of death included high
E/CO2, low
chronotropic index, low O2, low resting
systolic blood pressure, and older age.
Nonparametric Kaplan-Meier plots demonstrated that by
dividing the population according to peak
E/CO2 and peak
O2, it is possible to identify low,
intermediate, and very high risk groups. In
multivariate analyses, the only independent
predictors of death were high
E/CO2 (adjusted
relative risk [RR] 3.20, 95% CI 1.95 to 5.26,
P<0.0001) and low chronotropic index (adjusted RR 1.94,
95% CI 1.18 to 3.19, P=0.0009).
Conclusions—The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.
Key Words: heart failure • mortality • exercise • heart rate • ventilation
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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Currently 3.5 million people carry the diagnosis of heart failure in the United States, and the number is expected to increase to 6 million by the year 2030.1 As cardiac transplantation has become a viable treatment option for patients with end-stage disease, it has become more incumbent on physicians to acquire precise prognostic information in order to provide accurate risk stratification.2 Although several potential predictive variables have been studied, functional capacity, as defined by direct measurement of maximal oxygen consumption, has emerged as the most consistent and powerful predictor of mortality.3 4 5 Recently, reduced heart rate variability, as well as abnormal ventilatory and heart rate responses to exercise, have been found to be common in patients with severe heart failure.6 7 8 Whether they provide additional prognostic information, either alone or in combination, over peak oxygen consumption has not been well studied. Therefore, the purpose of this study was to carefully examine the predictive properties of the chronotropic and ventilatory responses to exercise among patients referred for exercise testing who manifest chronic heart failure.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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Study Population
The heart failure study cohort consisted of consecutive adults aged 18 to 70 who suffered from chronic heart failure and were referred for metabolic stress testing as part of a heart transplant evaluation. Patients were excluded if taking beta-adrenergic blockers or intravenous inotropes. For comparative purposes, a control cohort of 17 healthy adults underwent metabolic stress testing as well.
Clinic Data
Before each metabolic stress test, a structured
interview and chart review yielded data on demographics, left
ventricular ejection fraction, medications, cause of heart
failure, standard cardiac risk factors, and other comorbidities. The
definition of hypertension was based on JNC V criteria,9
whereas chart review and use of hypoglycemic medications established
the diagnosis of diabetes.
Exercise Testing
Symptom-limited metabolic stress testing was
performed according to the Naughton protocol and recorded on a
MedGraphics cardiopulmonary system. Measurements of oxygen
consumption (O2), carbon
dioxide production
(CO2), heart rate, minute
ventilation (E), tidal volume
(T), end-tidal carbon dioxide tension
(PETCO2), end tidal oxygen tension
(PETO2), and respiratory rate were
made after steady state at rest and every 30 seconds during exercise.
Also, during each stage of exercise, data on symptoms, rhythm, blood
pressure (by indirect sphygmomanometry), and ST segment changes were
prospectively collected. The ventilatory response to exercise was
defined as the value of
E/CO2 at
peak exercise. Anaerobic threshold was determined by
V-slope method if possible,10 otherwise, by inspection of
ventilatory equivalents.11 Patients were encouraged to
exercise to a respiratory exchange ratio (ie,
CO2/O2)
1.09.
Heart Rate Response to Exercise
Typically, the age-predicted maximum heart rate follows a linear
regression equation, eg, 200 minus age in years. The problem with
simply dividing peak heart rate by age-predicted maximum heart rate is
that this value is significantly confounded by effects of age, resting
heart rate, and most importantly, physical fitness.12
Wilkoff has described a method for describing the exercise heart rate response that takes advantage of the linear relation between exercise heart rate and metabolic work.13 Before exercise, a person has a certain metabolic reserve which is the difference between his peak oxygen consumption (or exercise capacity) and his rest oxygen consumption, typically 3.5 mL · kg-1 · min-1, or 1 metabolic equivalent (MET). As exercise progresses, that metabolic reserve is used up. Analogously, at rest there is a potential heart rate reserve, which is the difference between the peak attainable heart rate (as estimated, for example, by 220 minus age) and the resting heart rate. As exercise progresses heart rate reserve (HRR), like the metabolic reserve, is used up as well.
Thus, during any given stage of exercise, the percent
metabolic reserve (MR) used can be expressed as:
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1 and a 95% CI of 0.8 to 1.3.13 This
chronotropic index accounts for age, resting heart rate, and functional
capacity, and its value is independent of the stage of exercise
considered or the protocol used.12 13 For the current
study, peak exercise values were used.
End Points
The primary end point was death due to any cause; patients who
underwent transplantation were censored on their transplant date. Vital
status was assessed by (1) interrogation of the hospital information
system, (2) phone calls to patients, next of kin, or primary
physicians, and (3) search of the social security master
files.14 Vital status was confirmed in >98% of
patients.
Statistical Analyses
Cut-off values for high
E/CO2, low
chronotropic index, low peak
O2, low ejection fraction,
short stature, low body weight, resting tachycardia, and
low resting blood pressure were based on 75th or 25th percentiles as
appropriate. The 75th and 25th percentile values were derived from the
heart failure cohort. For descriptive purposes, baseline and exercise
characteristics were divided according to normal or abnormally high
E/CO2.
Variables thought to be related to death were analyzed
using the Kaplan-Meier approach with formal testing by the log-rank
test and univariate Cox regression analyses. After
confirming the validity of the proportional hazard assumption,
multivariate Cox regression models were used to assess
the importance of
E/CO2,
chronotropic index, peak O2,
and other possible predictors of death. Model construction was based on
a stepwise approach with initial selection of covariates on the basis
of results of univariate analyses. The key
variables of interest, namely
E/CO2,
chronotropic index, and peak
O2, were assessed using both
categorical and continuous approaches; for continuous
approaches, logarithmic and inverse transformations were
analyzed and found not to improve prediction of death. To avoid
model overfitting, no more than 1 covariate per 10 outcome events were
considered in regression models.
The ventilatory response to exercise is dependent on ventilatory drive,
physiological dead space, and patient motivation to
drive exercise beyond the anaerobic threshold. In order to
eliminate potential confounding from the last factor, supplementary
analyses were performed relating values of
E/CO2 at
rest and at anaerobic threshold. These analyses
were confined to the 406 patients in whom anaerobic
threshold could be determined. Pearson correlation analyses
were used to assess the association between peak and submaximal
values.
To analyze the association of peak
E/CO2 and
mortality in a continuous manner, a wholly parametric approach
was used.15 One phase of constant hazard was identified
indicating that an exponential model worked well. Modeling of peak
E/CO2 and
mortality included testing of logarithmic, threshold, inverse, and
quadratic transformations after inspection of log odds of risk
across quintiles of peak
E/CO2. A
plot of estimated 18-month survivals for different conditions was
constructed along with one standard error confidence limits.
All analyses were performed using the SAS 6.12 system (SAS,
Inc). Statistical comparisons were considered significant for
probability value 
0.01. Parametric hazards analyses
were performed using PROC HAZARD and PROC HAZPRED (available from
ftp://uabcvsr.cvsr.uab.edu).
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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Baseline Characteristics
There were 470 heart failure patients eligible for analyses (72% men, age 52±11 years, ejection fraction 21±8%, median peak
O2 17.2
mL · kg-1 ·
min-1 with 25th and 75th percentile 13.9 and
21.4 mL · kg-1 ·
min-1, respectively). A respiratory exchange
ratio of 1.09 was reached in 79% of the patients, whereas 90%
reached a value of 1.02. The majority of patients (65%) had a
nonischemic cause of left ventricular dysfunction.
Hypertension and atrial fibrillation were present in 38% and 6%
of patients, respectively. Most patients were receiving standard
therapy with angiotensin-converting enzyme
inhibitors (86%), digoxin (81%), and diuretics
(79%). Only 6% of patients were taking calcium channel blockers.
Compared with 17 healthy controls (Table 1
), the heart failure patients
had markedly higher resting heart rate and peak
E/CO2 and
markedly lower peak O2, peak
heart rate, peak systolic blood pressure, and chronotropic
index. Of note, the respiratory exchange ratios and the peak
respiratory rates were similar in the 2 groups.
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Baseline characteristics according to value of peak
E/CO2 are
summarized in Table 2. Patients who had an abnormally
high E/CO2
were more likely to be older, have a history of coronary artery
disease, and have lower resting systolic blood pressure, higher
resting heart rate, and a lower ejection fraction. There were no marked
differences between the 2 groups with respect to history of smoking,
hypertension, diabetes, or atrial fibrillation.
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Baseline exercise characteristics according to peak
E/CO2 are
summarized in Table 3. Patients with an abnormal
E/CO2 had a
lower exercise capacity (lower peak
O2 and
O2 at anaerobic
threshold), a lower peak systolic blood pressure and heart
rate, as well as a lower chronotropic index and lower peak
E. There was no difference in the respiratory
exchange ratio between the 2 groups.
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Correlation Analyses
Peak O2 was found to have
at least a moderate correlation with
E/CO2
(r=-0.64) and chronotropic index (r=0.58). The
correlation was more modest between
E/CO2
and chronotropic index (r=-0.39). Left
ventricular ejection fraction had very weak correlations
with
E/CO2
(r=-0.23), chronotropic index (r=0.09), and peak
O2
(r=0.15).
Predictors of Mortality
Univariate predictors of death are found in Table 4. An abnormally high peak
E/CO2
(44.7) was the strongest predictor of death. Analyses of the
Kaplan-Meier survival curves (Figure 1)
revealed a 1.5-year survival rate of 90% for those with a normal peak
E/CO2,
compared with only 67% for those with an abnormal value. A low
chronotropic index and a low peak
O2 also predicted higher
mortality rates (Table 4, Figures 2 and 3).
Resting systolic blood pressure, low ejection fraction, and
older age were weaker predictors of death.
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Combination of Risks and Mortality
When evaluating the significance of any combination of an
abnormally high
E/CO2, low
peak O2, and low chronotropic
index, an abnormally high
E/CO2
combined with a low chronotropic index was associated with the highest
risk of death (Figure 4). Combinations of
an abnormally high
E/CO2 and a
low peak O2 (Figure 5) and a low chronotropic index and a low
peak O2 (Figure 6) also identified groups at very high
and relatively low risks for death.
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Multivariate Analyses
Results of stepwise multivariate proportional
hazards analyses are summarized in Table 5. After
adjusting for low peak O2,
age, sex, history of coronary artery disease, and resting
systolic blood pressure, only an abnormally high
E/CO2 and a
low chronotropic index remained independently predictive of death. When
peak O2 was forced into the
regression model, again only a high
E/CO2 and a
low chronotropic index were predictive of death. When covariates were
analyzed in a continuous manner, only
E/CO2,
chronotropic index, and resting systolic blood pressure were
predictive; peak O2 was not
associated with death.
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When transplanted patients were excluded from the analyses, multivariate models yielded essentially identical results. There were no significant interactions found between any of the variables considered for prediction of mortality.
Associations of Resting and Submaximal
E/CO2 With
Mortality
Among the 406 patients for whom anaerobic threshold
could be determined, resting and anaerobic threshold values
of E/CO2
were higher when the peak value was abnormally high (Table 3
).
There was a strong correlation between peak and anaerobic
threshold values (r=0.86) with a less strong correlation
with resting values (r=0.66). Resting, anaerobic
threshold, and peak values of
E/CO2
were all associated with mortality (Table 6), with the
anaerobic threshold value almost as strong a predictor as
the peak value. After adjustment for potential confounders, the
anaerobic threshold and peak values remained predictive of
mortality (Table 6).
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Peak E/CO2 as a
Continuous Variable
When considered as a continuous variable, peak
E/CO2 had a
range of 15 to 84 with 5th, 25th, 50th, 75th, and 95th percentile
values of 27, 33, 38, 45, and 58, respectively. A parametric
model found that independent predictors of mortality included peak
E/CO2
(P=0.02), resting systolic blood pressure
(P=0.02), and male gender (P=0.03). Weaker
predictors were chronotropic index (P=0.06) and peak
O2 (0.07). A plot of
estimated 18-month survival according to values of peak
E/CO2
and peak O2 is shown in
Figure 7. Of note, a threshold effect was
noted whereby the mortality impact of peak
E/CO2
becomes particularly marked at values exceeding 40 to 45.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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Principal Findings
Abnormal ventilatory and chronotropic responses to exercise were powerful and independent predictors of mortality. Although both a high
E/CO2 and a
low chronotropic index were associated with a low peak
O2, in both
univariate and multivariate
analyses, these 2 values emerged as substantially stronger
correlates of death.
There were 2 other findings of note. First, the value of
E/CO2
obtained at submaximal exercise, namely at anaerobic
threshold, was almost as strong an independent predictor of mortality
as the peak value. Second, a parametric analysis of
peak E/CO2
considered as a continuous variable revealed a threshold pattern,
in which the mortality impact increased markedly at values exceeding 40
to 45.
Previous Findings
Several groups have reported that patients with severe heart
failure manifest an impaired heart rate variability at
rest16 and blunted heart rate responses to
exercise,8 both of which are thought to be reflective of
underlying autonomic dysfunction.12 Clark and Coats
reported that chronotropic incompetence was evident in nearly 30% of
heart failure patients they studied, but concluded it played a
significant role in exercise intolerance in only a minority of these
patients.17 Additionally, it has been shown that heart
failure patients hyperventilate abnormally during
exercise.18 More recently, the presence of a strong
association between decreased resting heart rate variability and
exercise hyperventilation has been used to argue that the latter is
also a result of autonomic dysfunction.19
To date, peak O2 has been one
of the gold standards by which heart failure patients are risk
stratified and is considered by many to be the key component of initial
heart transplant evaluation.3 5 20 21 22 Recently, both an
abnormally high
E/CO2 and
depressed heart rate variability have been reported to be associated
with an increased risk of death in heart failure
patients.6 7
The current study extends on these previous reports in several
important respects. First, we found that an abnormally high
E/CO2
predicts an increased risk of death among patients with severe heart
failure to an even greater degree than a reduced peak
O2. Second, a low chronotropic
index, a measure of exercise heart rate response which accounts for
effects of age, resting heart rate, and functional capacity, was at
least as strong a predictor of death as peak
O2. Third, when peak
E/CO2,
chronotropic index, and peak
O2 were considered together,
the ventilatory and chronotropic responses to exercise emerged as
stronger and independent predictors of death. The independent
predictive power of these 2 values indicate that they are not simply a
function of lower workload achieved.
Possible Mechanisms
The mechanisms underlying an abnormally high
E/CO2 in
patients with heart failure are thought to be multifactorial and have
been reported to include abnormalities among the following: central
neurogenic drive, central chemoreceptors, cardiac mechanoreceptors,
muscle ergoreceptors, anatomical and physiological
dead space, and peripheral
chemoreceptors.18 23 24 The
E/CO2
value is also reported to be independent of motivation with little
change in value at 30%, 60%, and 100% of exercise
capacity.18 In the present study, the prognostic
superiority of
E/CO2 over
peak O2 therefore may reflect
the ability of this value to exclude those patients with a falsely low
peak O2 secondary to a lack of
motivation or peripheral skeletal muscle dysfunction. In
this regard, it is noteworthy that anaerobic threshold
values of
E/CO2 were
closely correlated with peak values and were almost as strongly
predictive of death. Alternatively, it is possible that the underlying
abnormalities of autonomic dysfunction associated with both abnormal
ventilatory and chronotropic responses to exercise are distinct and
more closely related to outcome.
It is noteworthy that peak respiratory rates in heart failure patients
were similar to those of controls. This suggests that elevated levels
of peak
E/CO2 in
patients with severe heart failure may be due more to increased dead
space rather than to abnormalities of ventilatory drive. Thus,
E/CO2 may
be a better predictor of mortality as decreased cardiac output and
elevated diastolic filling pressures may directly cause
increased dead space in the form of interstitial edema and
pulmonary endothelial dysfunction, whereas peak
O2 is a function of either
central or peripheral abnormalities.
Limitations
The follow-up period for our study was relatively short; we are
unable to comment on the effects of the ventilatory and chronotropic
responses to exercise over >2 years of follow-up. Ejection fraction
data were not obtained in a uniform manner among all patients;
nonetheless, ejection fraction emerged as a relatively weaker predictor
of outcome.
Another concern is that physicians would respond to low peak
O2 by listing patients for
transplantation, thereby attenuating the association between peak
O2 and death. Peak
E/CO2
values were not considered in clinical decision-making at the time
these patients were evaluated. When we excluded the 46 patients who
were censored because of transplantation, the associations relating
ventilatory and chronotropic responses to mortality were unchanged.
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Conclusions |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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An abnormally high
E/CO2 and
an abnormally low chronotropic index are both strong predictors of
death among heart failure patients; their prognostic significance is
independent of peak O2. Future
research should focus on: (1) the influence of standard medical therapy
(digoxin, ACE inhibitors, and diuretics), as well
as, burgeoning therapies (ß-adrenergic blockers,
aldosterone inhibitors, and central active
sympathoinhibitory agents) on chronotropic response and
E/CO2, and
(2) how best to routinely incorporate chronotropic index and
E/CO2 into
heart failure staging and cardiac transplant evaluations.
Received May 3, 1999; revision received July 8, 1999; accepted July 28, 1999.
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References |
|---|
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
1. Robbins MA, O’Connell JB. Economic impact of heart failure. In: Rose EA, Stevenson LW, eds. Management of End-Stage Heart Disease. Philadelphia: Lippincott-Raven; 1998:3–13.
2. Evens RW. Cardiac replacement: estimation of need, demand, and supply. In: Rose EA, Stevenson LW, eds. Management of End-Stage Heart Disease. Philadelphia: Lippincott-Raven; 1998:13–25.
3. Myers J, Gullestad L. The role of exercise testing and gas-exchange measurement in the prognostic assessment of patients with heart failure. Curr Opin Cardiol. 1998;13:145–155.[Medline] [Order article via Infotrieve]
4. Francis GS. Determinants of prognosis in patients with heart failure. J Heart Lung Transplant. 1994;13:S113–116.[Medline] [Order article via Infotrieve]
5.
Myers J, Gullestad L, Vagelos R, Do D, Bellin D, Ross
H, Fowler MB. Clinical, hemodynamic, and
cardiopulmonary exercise test determinants of survival in
patients referred for evaluation of heart failure. Ann Intern
Med. 1998;129:286–293.
6. Chua TP, Ponikowski P, Harrington D, Anker SD, Webb-Peploe K, Clark AL, Poole-Wilson PA, Coats AJ. Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol. 1997;29:1585–1590.[Abstract]
7.
Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P,
Mullen M, Baig W, Flapan AD, Cowley A, Prescott RJ, Neilson JM, Fox KA.
Prospective study of heart rate variability and mortality in chronic
heart failure: results of the United Kingdom Heart Failure Evaluation
and Assessment of Risk Trial (UK-Heart). Circulation. 1998;98:1510–1516.
8.
Colucci WS, Ribeiro JP, Rocco MB, Quigg RJ, Creager
MA, Marsh JD, Gauthier DF, Hartley LH. Impaired chronotropic response
to exercise in patients with congestive heart failure: role of
postsynaptic beta-adrenergic desensitization. Circulation. 1989;80:314–323.
9.
The fifth report of the Joint National Committee on
Detection, Evaluation, and Treatment of High Blood Pressure (JNC V)
[see comments]. Arch Intern Med. 1993;153:154–183.
10.
Beaver WL, Wasserman K, Whipp BJ. A new method for
detecting anaerobic threshold by gas exchange. J
Appl Physiol. 1986;60:2020–2027.
11. Wasserman K. Breathing during exercise. N Engl J Med. 1978;298:780–785.[Medline] [Order article via Infotrieve]
12.
Lauer MS, Okin PM, Larson MG, Evans JC, Levy D.
Impaired heart rate response to graded exercise: prognostic
implications of chronotropic incompetence in the Framingham Heart
Study. Circulation. 1996;93:1520–1526.
13. Wilkoff BL, Miller RE. Exercise testing for chronotropic assessment. Cardiol Clin. 1992;10:705–717.[Medline] [Order article via Infotrieve]
14.
Curb JD, Ford CE, Pressel S, Palmer M, Babcock C,
Hawkins CM. Ascertainment of vital status through the National Death
Index and the Social Security Administration. Am J
Epidemiol. 1985;121:754–766.
15. Blackstone EH, Naftel DC, Turner ME. The decomposition of time-varying hazard into phases, each incorporating a separate stream on concomitant information. J Am Stat Soc. 1986;81:615–624.
16.
Wijbenga JA, Balk AH, Meij SH, Simoons ML, Malik M.
Heart rate variability index in congestive heart failure: relation to
clinical variables and prognosis. Eur Heart J. 1998;19:1719–1724.
17. Clark AL, Coats AJ. Chronotropic incompetence in chronic heart failure. Int J Cardiol. 1995;49:225–231.[Medline] [Order article via Infotrieve]
18. Metra M, Dei Cas L, Panina G, Visioli O. Exercise hyperventilation chronic congestive heart failure, and its relation to functional capacity and hemodynamics [see comments]. Am J Cardiol. 1992;70:622–628.[Medline] [Order article via Infotrieve]
19. Ponikowski P, Chua TP, Piepoli M, Banasiak W, Anker SD, Szelemej R, Molenda W, Wrabec K, Capucci A, Coats AJ. Ventilatory response to exercise correlates with impaired heart rate variability in patients with chronic congestive heart failure. Am J Cardiol. 1998;82:338–344.[Medline] [Order article via Infotrieve]
20.
Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH Jr,
Wilson JR. Value of peak exercise oxygen consumption for optimal timing
of cardiac transplantation in ambulatory patients with heart failure.
Circulation. 1991;83:778–786.
21.
Roul G, Moulichon ME, Bareiss P, Gries P, Sacrez J,
Germain P, Mossard JM, Sacrez A. Exercise peak VO2 determination in
chronic heart failure: is it still of value? Eur Heart
J. 1994;15:495–502.
22. Stelken AM, Younis LT, Jennison SH, Miller DD, Miller LW, Shaw LJ, Kargl D, Chaitman BR. Prognostic value of cardiopulmonary exercise testing using percent achieved of predicted peak oxygen uptake for patients with ischemic and dilated cardiomyopathy. J Am Coll Cardiol. 1996;27:345–352.[Abstract]
23. Reindl I, Wernecke KD, Opitz C, Wensel R, Konig D, Dengler T, Schimke I, Kleber FX. Impaired ventilatory efficiency in chronic heart failure: possible role of pulmonary vasoconstriction. Am Heart J. 1998;136:778–785.[Medline] [Order article via Infotrieve]
24.
Clark AL, Chua TP, Coats AJ. Anatomical dead space,
ventilatory pattern, and exercise capacity in chronic heart failure.
Br Heart J. 1995;74:377–380.
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 R. V. Milani, C. J. Lavie, M. R. Mehra, and H. O. Ventura Understanding the Basics of Cardiopulmonary Exercise Testing Mayo Clin. Proc., December 1, 2006; 81(12): 1603 - 1611. [Abstract] [Full Text] [PDF]
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J A Laukkanen, S Kurl, J T Salonen, T A Lakka, and R Rauramaa Peak oxygen pulse during exercise as a predictor for coronary heart disease and all cause death Heart, September 1, 2006; 92(9): 1219 - 1224. [Abstract] [Full Text] [PDF]
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D. Messika-Zeitoun, B. D. Johnson, V. Nkomo, J.-F. Avierinos, T. G. Allison, C. Scott, A. J. Tajik, and M. Enriquez-Sarano Cardiopulmonary Exercise Testing Determination of Functional Capacity in Mitral Regurgitation: Physiologic and Outcome Implications J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2521 - 2527. [Abstract] [Full Text] [PDF]
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S. N. Nanas, J. N. Nanas, D. Ch. Sakellariou, S. K. Dimopoulos, S. G. Drakos, S. G. Kapsimalakou, C. A. Mpatziou, O. G. Papazachou, A. S. Dalianis, M. I. Anastasiou-Nana, et al. VE/VCO2 slope is associated with abnormal resting haemodynamics and is a predictor of long-term survival in chronic heart failure Eur J Heart Fail, June 1, 2006; 8(4): 420 - 427. [Abstract] [Full Text] [PDF]
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K K A Witte, J G F Cleland, and A L Clark Chronic heart failure, chronotropic incompetence, and the effects of {beta} blockade Heart, April 1, 2006; 92(4): 481 - 486. [Abstract] [Full Text] [PDF]
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L. C. Davies, R. Wensel, P. Georgiadou, M. Cicoira, A. J.S. Coats, M. F. Piepoli, and D. P. Francis Enhanced prognostic value from cardiopulmonary exercise testing in chronic heart failure by non-linear analysis: oxygen uptake efficiency slope Eur. Heart J., March 2, 2006; 27(6): 684 - 690. [Abstract] [Full Text] [PDF]
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R. L. Bard, M. S. Lauer, J. O. O'Neill, C. E. Pothier, and J. B. Young Letter Regarding Article by O'Neill et al, "Peak Oxygen Consumption as a Predictor of Death in Patients With Heart Failure Receiving {beta}-Blockers" * Response Circulation, October 18, 2005; 112(16): e271 - e271. [Full Text] [PDF]
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M. Guazzi, G. Reina, G. Tumminello, and M. D. Guazzi Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients Eur J Heart Fail, October 1, 2005; 7(6): 1017 - 1022. [Abstract] [Full Text] [PDF]
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J. O. O'Neill, J. B. Young, C. E. Pothier, and M. S. Lauer Peak Oxygen Consumption as a Predictor of Death in Patients With Heart Failure Receiving {beta}-Blockers Circulation, May 10, 2005; 111(18): 2313 - 2318. [Abstract] [Full Text] [PDF]
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M. Guazzi, G. Reina, G. Tumminello, and M. D. Guazzi Exercise ventilation inefficiency and cardiovascular mortality in heart failure: the critical independent prognostic value of the arterial CO2 partial pressure Eur. Heart J., March 1, 2005; 26(5): 472 - 480. [Abstract] [Full Text] [PDF]
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P. d. Groote, J. Dagorn, B. Soudan, N. Lamblin, E. Mc Fadden, and C. Bauters Reply J. Am. Coll. Cardiol., January 4, 2005; 45(1): 163 - 164. [Full Text] [PDF]
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 M. Guazzi, S. Belletti, G. Tumminello, C. Fiorentini, and M. D. Guazzi Exercise hyperventilation, dyspnea sensation, and ergoreflex activation in lone atrial fibrillation Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2899 - H2905. [Abstract] [Full Text] [PDF]
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W. T. Abraham, J. B. Young, A. R. Leon, S. Adler, A. J. Bank, S. A. Hall, R. Lieberman, L. B. Liem, J. B. O'Connell, J. S. Schroeder, et al. Effects of Cardiac Resynchronization on Disease Progression in Patients With Left Ventricular Systolic Dysfunction, an Indication for an Implantable Cardioverter-Defibrillator, and Mildly Symptomatic Chronic Heart Failure Circulation, November 2, 2004; 110(18): 2864 - 2868. [Abstract] [Full Text] [PDF]
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 U. Corra, A. Mezzani, E. Bosimini, and P. Giannuzzi Cardiopulmonary Exercise Testing and Prognosis in Chronic Heart Failure*: A Prognosticating Algorithm for the Individual Patient Chest, September 1, 2004; 126(3): 942 - 950. [Abstract] [Full Text] [PDF]
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J. O. O'Neill, J. B. Young, C. E. Pothier, and M. S. Lauer Severe frequent ventricular ectopy after exercise as a predictor of death in patients with heart failure J. Am. Coll. Cardiol., August 18, 2004; 44(4): 820 - 826. [Abstract] [Full Text] [PDF]
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R. V. Milani, C. J. Lavie, and M. R. Mehra Cardiopulmonary Exercise Testing: How Do We Differentiate the Cause of Dyspnea? Circulation, July 27, 2004; 110(4): e27 - e31. [Full Text] [PDF]
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B. Azarbal, S. W. Hayes, H. C. Lewin, R. Hachamovitch, I. Cohen, and D. S. Berman The incremental prognostic value of percentage of heart rate reserve achieved over myocardial perfusion single-photon emission computed tomography in the prediction of cardiac death and all-cause mortality: Superiority over 85% of maximal age-predicted heart rate J. Am. Coll. Cardiol., July 21, 2004; 44(2): 423 - 430. [Abstract] [Full Text] [PDF]
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R. Wolk, B. D. Johnson, and V. K. Somers Leptin and the ventilatory response to exercise in heart failure J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1644 - 1649. [Abstract] [Full Text] [PDF]
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R. Arena, J. Myers, S. S. Aslam, E. B. Varughese, and M. A. Peberdy Technical Considerations Related to the Minute Ventilation/Carbon Dioxide Output Slope in Patients With Heart Failure Chest, August 1, 2003; 124(2): 720 - 727. [Abstract] [Full Text] [PDF]
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P A Poole-Wilson, B F Uretsky, K Thygesen, J G F Cleland, B M Massie, and L Ryden Mode of death in heart failure: findings from the ATLAS trial Heart, January 1, 2003; 89(1): 42 - 48. [Abstract] [Full Text] [PDF]
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P. Agostoni, M. Guazzi, M. Bussotti, S. De Vita, and P. Palermo Carvedilol Reduces the Inappropriate Increase of Ventilation During Exercise in Heart Failure Patients Chest, December 1, 2002; 122(6): 2062 - 2067. [Abstract] [Full Text] [PDF]
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A. Cohen-Solal, J.Y. Tabet, D. Logeart, P. Bourgoin, M. Tokmakova, and M. Dahan A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure Eur. Heart J., May 2, 2002; 23(10): 806 - 814. [Abstract] [Full Text] [PDF]
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A. Koike, H. Itoh, M. Kato, H. Sawada, T. Aizawa, L. T. Fu, and H. Watanabe Prognostic Power of Ventilatory Responses During Submaximal Exercise in Patients With Chronic Heart Disease* Chest, May 1, 2002; 121(5): 1581 - 1588. [Abstract] [Full Text] [PDF]
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M Guazzi, G Pontone, R Brambilla, P Agostoni, and G Reina Alveolar-capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure Eur. Heart J., March 2, 2002; 23(6): 467 - 476. [Abstract] [Full Text] [PDF]
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S.G Williams, G.A Cooke, D.J Wright, W.J Parsons, R.L Riley, P Marshall, and L-B Tan Peak exercise cardiac power output; a direct indicator of cardiac function strongly predictive of prognosis in chronic heart failure Eur. Heart J., August 2, 2001; 22(16): 1496 - 1503. [Abstract] [PDF]
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 V. Conraads, C. Vrints, J. C. Daubert, S. Cazeau, and C. Leclercq Biventricular Pacing in Patients with Heart Failure N. Engl. J. Med., July 26, 2001; 345(4): 293 - 294. [Full Text] [PDF]
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D P Francis, L C Davies, and A J S Coats Diagnostic exercise physiology in chronic heart failure Heart, July 1, 2001; 86(1): 17 - 20. [Full Text] [PDF]
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N. de Jonge, H. Kirkels, J. R. Lahpor, C. Klopping, E. J. Hulzebos, A. Brutel de la Riviere, and E. O. Robles de Medina Exercise performance in patients with end-stage heart failure after implantation of a left ventricular assist device and after heart transplantation: An outlook for permanent assisting? J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1794 - 1799. [Abstract] [Full Text] [PDF]
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F. J. Meyer, M. M. Borst, C. Zugck, A. Kirschke, D. Schellberg, W. Kubler, and M. Haass Respiratory Muscle Dysfunction in Congestive Heart Failure : Clinical Correlation and Prognostic Significance Circulation, May 1, 2001; 103(17): 2153 - 2158. [Abstract] [Full Text] [PDF]
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Recommendations for exercise testing in chronic heart faliure patients Eur. Heart J., January 1, 2001; 22(1): 37 - 45. [PDF]
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G. A. MacGowan, S. Murali, M. S. Lauer, M. Robbins, F. Pashkow, K. Hoercher, C. E. Snader, J. B. Young, and G. Francis Ventilatory and Heart Rate Responses to Exercise: Better Predictors of Heart Failure Mortality Than Peak Exercise Oxygen Consumption Response Circulation, December 12, 2000; 102 (24): e182 - e182. [Full Text] [PDF]
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