The n e w e ng l a n d j o u r na l of m e dic i n e

Edi t or i a l s

Exercise for Frail, Elderly Patients with Acute

Heart Failure — A Strong Step Forward
Stefan D. Anker, M.D., Ph.D., and Andrew J.S. Coats, D.M.

Exercise rehabilitation has a long history in the
management of chronic heart failure, with the
first randomized trial of exercise training dating
back to 19901 — and by the late 1990s, it had
become an integral part of therapy.2 There is
solid evidence from multiple trials and meta-
analyses that exercise training improves exercise
capacity and reduces symptoms in patients with
stable heart failure. However, trial data showing
a reduction in the risk of hospitalization or death
in patients with heart failure who participated in
exercise training are lacking, although the results
from a large trial, HF-ACTION (Heart Failure:
A Controlled Trial Investigating Outcomes of
Exercise Training), came close.3
Exercise is not like a drug. There is no stan-
dard dose, formulation, or frequency of adminis-
tration, and it has many variations, all of which
depend crucially on patient motivation to elicit
beneficial effects. To reduce variability, trials in
heart failure frequently exclude elderly patients
with multiple coexisting conditions, unstable
clinical status, or frailty. Thus, the patients with
the greatest need are rarely studied.
The Rehabilitation Therapy in Older Acute
Heart Failure Patients (REHAB-HF) trial by Kitz­
man and colleagues, which is now reported in
the Journal,4 takes our knowledge forward. This
trial evaluated a rehabilitation intervention that
included multiple physical-function domains, with
a training regimen that was based on patients’
individual abilities. The trial population com-
prised mostly frail or prefrail patients with an
average of five coexisting conditions; the mean
age was 73 years. The intervention was com-
menced during, or early after, hospitalization for
acute heart failure, provided that the patient
could walk at least 4 m. The population studied
was severely limited; at baseline, the mean
6-minute walk distance was less than 200 m in
both the intervention group and the usual care
(control) group, and the mean scores on the
Kansas City Cardiomyopathy Questionnaire
(KCCQ) were 40 and 42, respectively (scores on
the KCCQ range from 0 to 100, with higher
scores indicating better health status). The list of
exclusion criteria was very short. We congratulate
the authors for having developed a program that
is pragmatic, widely applicable, and able to be
duplicated relatively easily in practice.
The recruitment period of 5 years seems long
at first glance, but the trial was conducted at
only three lead clinical centers and four satellite
sites; hence, an average recruitment rate of ap-
proximately 0.8 patients per site per month seems
to have been achieved, which is two to three
times as fast as the rates achieved in many other
trials in heart failure. The limited number of
sites also provided an advantage, in that quality
control for functional testing of the patients
could be maintained more easily.
The primary outcome was assessed at 3 months
— a short but appropriate interval. In the con-
text of a clinical trial, exercise interventions are
often hampered by reduced adherence over the
long term. In the REHAB-HF trial, among the pa-
tients who had been randomly assigned to the
rehabilitation intervention, the number who dis­
continued the intervention prematurely was much
greater than the number who died.
An exercise intervention cannot be double-
blinded, but the results presented by Kitzman et al.

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 Editorials
are convincing with respect to the outcomes
measured and the magnitude of improvement.
The primary outcome of the REHAB-HF trial
was the score on the Short Physical Performance
Battery (total scores range from 0 to 12, with
lower scores indicating more severe physical
dysfunction) at 3 months. The Short Physical
Performance Battery is a standardized test that
is used to assess lower-body muscle function and
control in elderly persons. A score below 10 has
been shown to be predictive of an increased risk
of death in the general population5 (in this trial,
the baseline score was 6). Although the use of
this test in trials in heart failure is unusual, it is
very relevant for this cohort of elderly, frail pa-
tients with acute heart failure. The size of the
treatment effect is impressive. The observed
treatment-induced effect in this trial — a mean
between-group difference in the overall score of
1.5 points (P<0.001) — compares very favorably
with previously reported estimates of 0.27 to
0.55 points (indicating a small meaningful dif-
ference) and 0.99 to 1.34 points (indicating a
substantial difference).6 Similarly, the between-
group differences seen in 6-minute walk distance
(34 m) and gait speed (0.12 m/sec) are clinically
meaningful and sizable.
The observed benefit in the KCCQ overall
score (7.1 points) is substantial. We hypothesize
that part of the benefit may be due to better
physical performance and that part may be due to
improvements in psychosocial factors and mood.
It appears that exercise also resulted in patients
becoming happier — or at least less depressed,
as evidenced by the positive results on the Geri-
atric Depression Scale-15. This may be an inde-
pendently important finding; other therapies for
heart failure (e.g., telemedical interventions) have
been shown to be less effective among patients
with heart failure and depression than among
patients with heart failure who did not have de-
pression, a finding that has even led to the ex-
clusion of patients with major depression in some
trials.7
Also of interest is the possible effect on falls
(odds ratio for ≥1 fall, 0.67; 95% confidence in-
terval, 0.42 to 1.06). This is an intriguing and
potentially valuable added benefit, provided that
it can be validated in subsequent appropriately
powered trials.
Still, there are limits to the benefits seen with
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exercise in patients with acute heart failure. The
rates of hospitalization and death did not differ
substantially between the intervention group and
the control group, and perhaps this effect should
not be expected. Among outpatients with stable
heart failure, benefits of exercise training on the
risk of death have not been shown, and there is
no consensus with respect to the effects of exer-
cise on the risk of hospitalization for heart fail-
ure, with some analyses suggesting benefit 8 and
others failing to show benefit.9
The results presented by Kitzman and col-
leagues provide a compelling argument for the
adoption of exercise rehabilitation as standard
care, even for elderly, frail patients with acute
heart failure.
Disclosure forms provided by the authors are available with
the full text of this editorial at NEJM.org.
From the Department of Internal Medicine and Cardiology on
Campus Virchow–Klinikum, the Berlin Institute of Health Cen-
ter for Regenerative Therapies, and the German Center for Car-
diovascular Research partner site Berlin, Charité Universitäts-
medizin Berlin (S.D.A.); and the Faculty of Medicine, University
of Warwick, Coventry, United Kingdom (A.J.S.C.).
This editorial was published on May 16, 2021, at NEJM.org.
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DOI: 10.1056/NEJMe2106140
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