DISCUSSION
This is a meta-analysis of observational studies that included 589
patients with proven extra-cardiac sarcoidosis and no evidence of
cardiac involvement and 378 controls. The main findings of the study
were as follows: (i) The sarcoidosis group was associated with a
significantly reduced LVGLS compared to the control group, (ii) The
sarcoidosis group was associated with a significantly reduced LVGCS as
compared to the control group, and (iii) Within the sarcoid group, the
LVGLS was significantly lower in patients who suffered MCEs as compared
to those who did not.
CS manifests symptoms in as few as 5% of patients with sarcoidosis5. Cardiac involvement in patients with sarcoidosis is
characterized by three distinct histopathological stages: inflammation
or edema of the myocardium with mononuclear infiltration, non-caseating
granuloma formation, and finally fibrosis and scar
formation.4 CS primarily targets the left ventricular
free wall, papillary muscles and basal septum4,7.
Specifically, CS mostly affects the mid and epicardial myocardium, where
the myofibrils are arranged circumferentially in left-sided helical
structures.23 Later in the disease process, CS can
involve the sub-endocardial myofibrils. This explains the lagging in
ejection fraction reduction in patients with CS, which usually denotes
an extension of the scar4. Steroid therapy is the
standard therapy for patients with CS as it prevents left ventricular
remodeling and disease progression.23 However, Chiu et
al. noted that patients with CS and EF less than 30% are less likely to
benefit from steroids, as EF reduction indicates that scar remodeling
has occured.24 Thus, early detection and timely
intervention are essential.
In our study the LVGLS, which represents the disruption of the
longitudinally oriented myofibrils in these helical structures25, was impaired in the sarcoid group10,15,16. Kansal et al. demonstrated that LVGLS
impairment can be independent of the location of the scar as defined by
the late gadolinium enhancement (LGE) on CMR, and suggested a functional
component leading to this early impairment26.
Similarly, the GCS was significantly lower in the sarcoidosis group
versus controls. Ori et al. demonstrated that GCS could predict the
location of LGE on CMR when the mid-myocardium is
affected27.
Interestingly, two studies in our cohort demonstrated impairment of
LVGLS as compared to controls even in the absence of LGE17,18. Also, in the study by Schouver et al., only
8.6% of patients in the abnormal LVGLS group had positive findings on
CMR10. One explanation for this observation is that
LGE detects fibrosis or scar tissue which is histologically a late
finding of CS, while early inflammation or edema may not be detected
unless a T2-sequence was used 4,7. This is clinically
relevant, as an autopsy study of 84 patients demonstrated that even
microscopic myocardial sarcoidosis could account for arrhythmias and
sudden cardiac death.3
In a separate analysis of sarcoidosis patients that included studies,
LVGLS was significantly lower in patients who suffered MCEs as compared
to those who did not, despite having normal ejection fraction at
baseline.20,21,23,29 Myocardial strain can predict the
presence and the extent of LGE on CMR 23,27, and LGE
seems to be a strong predictor of adverse outcomes. 28A pooled HR for 3 studies demonstrated that a reduced(less negative)
LVGLS is predictive of MCEs, however this should be interpreted with
caution as this analysis included only 3
studies.20,21,, 29 The study by Murtagh et alsuggests that LVGLS more than -17% correlates with LGE on CMR and
predicts adverse outcomes.23
Our meta-analysis has certain limitations. The studies included were
observational which makes selection and observer bias inevitable. In
addition, significant heterogeneity was noted in the LVGLS and GCS
groups. This can be partly explained by the different vendors and
software used to detect strain. Patients included in the cohorts belong
to various age groups and different stages of sarcoidosis. We could not
account for this variation among studies, which raises concern over the
generalizability of our results.