Discussion
To our knowledge this is the largest to date meta-analysis investigating
the relationship between OSA and echocardiographic parameters of DD. An
association between obstructive sleep apnea DD parameters was
demonstrated which was independent of other risk factors.
Although cumulative data from observational studies have linked OSA with
increased risk of DD, it has been argued that this association is driven
mainly by the significant burden of cardiovascular risk factors observed
in patients with OSA. To overcome this argument, we only included
studies in which OSA patients were free from major cardiac risk factors.
Therefore, our study results suggest a direct relationship between OSA
and DD.
Of the numerous echocardiographic parameters mentioned, the American
society of echocardiography (ASE) guidelines gives prominence to that
the mitral inflow velocity ratios of E/A, e′ as an estimation of LV
filling pressure, left atrium volume index (LAVI), tricuspid
regurgitation velocity and deceleration time in the assessment of the
presence of DD. Two principal mechanisms are responsible for DD
including impaired ventricular relaxation and increased passive
myocardial stiffness (or decreased compliance). In grade I DD, there is
impaired relaxation due to increased stiffness of the left ventricular
chamber, resulting in slow early diastolic filling. LV relaxation is
affected by load, inactivation, and asynchrony. Increased LV afterload
leads to delayed and slow relaxation (6).
Sleep related breathing disorders including OSA exert a wide range of
deleterious cardiovascular effects via direct and indirectly mechanisms.
The repetitive episodes of apnea or hypopnea are associated with
intermittent hypoxia, hypercapnia, increasingly negative intrathoracic
pressure and sympathetic overdrive which all adversely affect the
cardiovascular system. The hemodynamic and metabolic sequela of OSA
result in endothelial dysfunction, increased inflammation,
atherogenesis, hypertension, arrhythmias, and increased left ventricular
transmural pressures. The combination of increased afterload and
elevated heart rate contribute to left ventricular hypertrophy. Patients
with OSA have been found to have increased levels of catecholamines and
aldosterone suggesting activation of the renin-angiotensin-aldosterone
axis (RAAS system), through the sympathetic overdrive, which in turn
leads to cardiac fibrosis and remodeling contributing to impairment of
myocardial relaxation, left ventricular stiffness and consequently to
DD(3).
In agreement with the results of our analysis is the study by Butt
et al (12) who provided a comprehensive assessment of LV structural and
functional parameters using 2D and 3D echocardiography in
moderate-severe OSA patients who were free of other concomitant
confounder morbidities. The study included 120 otherwise healthy
subjects with no evidence of cardiovascular disease, dyslipidemia or
diabetes mellitus and were stratified into 3 groups based on the
severity of sleep apnea and the presence of hypertension. The OSA group
which included patients with AHI >15 and no hypertension
(n=40) were compared with matched disease control subjects who had
essential hypertension but no OSA (N=40) and healthy control subjects
who had neither hypertension nor OSA (N=40). It was demonstrated that
patients with OSA and hypertension compared to the healthy subjects had
higher left ventricular mass index and impaired systolic (decreased S
systolic velocity) and diastolic function (E/A, IVRT, and E/e′). OSA
patients were also found to have greater LAVI and lower ejection
fraction as assessed by 3D echocardiography. Therapy with CPAP (mean
duration of 6 months) resulted in significant structural changes
(reduction in the LV mass and PWT/IVST) and improvement on the
echocardiographic parameters of systolic and diastolic function.
On the contrary Kim et al (18) in a similar study with 62
patients classified into 3 groups (mild to moderate OSA, severe OSA, and
control subjects) failed to detect significant correlation between OSA
and DD. It was found that patients with OSA had decreased early
diastolic velocity compared to control subjects but otherwise no
differences in terms of E/A, isovolumic relaxation time, deceleration
time, and pulmonary vein systolic/diastolic pulmonary vein velocity
ratio were detected among the groups. Masa JF in a prospective study
enrolled 196 patients with obesity hypoventilation syndrome and
concomitant OSA treated with either NIV or CPAP. It was demonstrated
that NIV and CPAP therapies improved left ventricular DD, reduced left
atrial diameter, and pulmonary artery pressures at 3 years suggesting an
association between sleep apnea and DD.
The prevalence of OSA has increased substantially in the past decade and
it is expected to continue to rise due to the obesity epidemic, yet it
is believed that OSA remains underdiagnosed (3). A major reason for
underdiagnosis is that most patients with heart failure (HF) and sleep
disordered breathing (SDB) do not complain of daytime sleepiness despite
having significantly less sleep time. Another important factor that is
that HF by itself or standard medications like beta-blockers in the
treatment of HF can also cause fatigue masking SDB symptoms and thus
offering an alternative to SDB leading to its underdiagnosis. This
highlights the need to adopt a low threshold to test for sleep apnea in
the context of HF.
With the increasing number of patients with HFpEF and the continued
focus on reducing the rate of associated hospital admissions,
comprehensive assessment of diastolic parameters and evaluation for
those patients with HFpEF is an important aspect of cardiac testing.
While all those with DD may not have HFpEF, when present this portends a
worse prognosis. Grading of diastolic function is an important predictor
of outcome. Longitudinal studies have shown an increased rate of
all-cause mortality in patients with DD (24). Redfield and associates
demonstrated an increased mortality risk in patients with DD when
controlled for age, sex, and EF (25).
Therefore, it appears the early recognition of DD and HFpEF would be of
clinical value, leading to more aggressive prevention and therapeutic
strategies to ameliorate HF related symptoms or reduce disease
progression. The association between OSA and DD underscores the need for
increased level of awareness of such association among clinicians, and
to have a low threshold for echocardiographic assessment of diastolic
function.
To date the treatment of DD is treatment of the underlying etiology. The
potential cardioprotective effects of CPAP or other therapy for OSA may
offer a therapeutic tool for the treatment of DD in patients with OSA.