Diastolic dysfunction is independently and strongly related to
reduced exercise capacity, a new cross-sectional study has shown [1].
And unlike many other factors associated with reduced exercise
capacity, diastolic dysfunction is modifiable and so may be a
preventable factor in the development of exercise intolerance, the
researchers point out.

Dr Jasmine Grewal (Mayo Clinic, Rochester, MN) and colleagues report
their findings in the January 21, 2009 issue of the Journal of the
American Medical Association. "This is the first time this has been
studied in a large number of patients, and it's the first time
[diastolic dysfunction] has been attempted to be related to exercise
capacity and age-related changes," senior author Dr Patricia A
Pellikka (Mayo Clinic, Rochester, MN) told heartwire.

Although she says the results need to be confirmed in prospective
trials, she says that they found "that even mild abnormalities of
diastolic function seemed to be related to a lower exercise capacity
and that the magnitude of the effect of diastolic abnormalities
became greater in older patients." This points to a potentially
modifiable factor that might be a target for interventions that could
maintain exercise capacity with aging, she says.

Diastolic Dysfunction Strongest Echocardiographic Correlate of
Exercise Tolerance

Grewal et al explain that many factors, such as advancing age, female
sex, greater body-mass index (BMI), and coexisting medical conditions
are known to be associated with a decrease in exercise capacity, but
elucidating the mechanisms of cardiac-related exercise limitation has
been technically difficult to date. Prior research has suggested that
measurements of left ventricular systolic function do not predict
maximal exercise time in people with normal or impaired left
ventricular systolic function.

Doppler echocardiography can now characterize left ventricular
diastolic function through a combination of measurements, they note,
and a few previous small studies have shown this to be correlated
with exercise capacity.

In their study, they assessed 2867 patients undergoing exercise
echocardiography with routine measurements of left ventricular
systolic and diastolic dysfunction by two-dimensional and Doppler
techniques. Analyses were conducted to determine the strongest
correlates of exercise capacity and the age and sex interactions of
these variables with exercise capacity. The main outcome measure was
exercise capacity in metabolic equivalents (METs).

Diastolic dysfunction was strongly and inversely correlated with
exercise capacity. Compared with normal function, after multivariate
adjustment, those with moderate/severe resting diastolic dysfunction
(-1.30 METs; p<0.001) and mild resting diastolic dysfunction (-0.70
METs; p<0.001) had substantially lower exercise capacity. Left
ventricular filling pressures were similarly associated with a
reduction in exercise capacity, each in separate multivariate
analyses.

Individuals with impaired relaxation (mild dysfunction) or left
ventricular filling pressure of E/e' 15 or greater had a progressive
increase in the magnitude of reduction in exercise capacity with
advancing age (p<0.001 and p=0.02, respectively). Other independent
correlates of exercise capacity were age, female sex, and BMI >30.

In this large consecutive population free of valvular heart disease
or exercise-induced ischemia referred for exercise echo, "we found
resting diastolic function to be the strongest echocardiographic
correlate of exercise tolerance," the researchers say. "This was
superseded only by the clinical factors of advancing age, female sex,
and increased BMI."

Forum moderator of theheart.org, Dr Melissa Walton-Shirley (TJ Samson
Hospital, Glasgow, KY), said: "Historically, our main focus as
cardiologists has been upon systolic dysfunction, and rightly
so . . . but this study highlights the importance of a new emphasis
on diastology and its implied role in both quality- and quantity-of-
life issues.

"When physicians have a better understanding of the physiology of
exercise intolerance, we can then translate that understanding to our
patients in the office setting or at the bedside. One of our greatest
responsibilities as healthcare providers is to convey the secrets of
wellness, longevity, and prevention to our patient population. Adult
cardiologists and pediatricians alike should take the time on a daily
basis to have these conversations that explain the negative effects
of obesity and inactivity to our patients and, more important, the
potential for reversibility of these entities," she adds.

ARBs May Have a Therapeutic Role To Play

"In identifying diastolic function parameters as strong correlates of
exercise capacity, we have identified potentially modifiable and
preventable factors in the development of exercise intolerance," the
researchers say. "It is well-known that exercise training improves
diastolic function in healthy individuals, [but] the effects of
training on diastolic dysfunction are less clear," they add.

Pellikka expanded upon this for heartwire: "Work needs to be done to
see if we can modify this age-related decline in exercise capacity.
We know certain risk factors--such as uncontrolled hypertension and
untreated coronary disease--will lead to diastolic dysfunction, so we
need to make sure we're treating those conditions aggressively.

"Patients with unexplained limitations of exercise capacity or
patients with exertional symptoms should have their diastolic
function assessed, and fortunately that is something that is widely
available and can be achieved with echo Doppler completely
noninvasively," she notes.

One possible therapy is angiotensin-receptor blockers (ARBs), she
says, which appear promising because they block the angiotensin II
action that is thought to be responsible for slowed left ventricular
relaxation during exercise.

"Although these data require confirmation in prospective studies,
they point to a potentially modifiable factor that might be a target
for interventions that could maintain exercise capacity with aging."


Grewal J, McCully RB, Kane GC, et al. Left ventricular function and
exercise capacity. JAMA 2009; 301:286-294.