Discussion
Main findings
This is the first study to systematically evaluate the risk factors in
developing LV dysfunction in patients with LV summit VA. In the present
study, we found that:(1) The incidence of LV dysfunction with VA
originated from LVS was 28.8%; (2) PVC QRS duration and AEAD were
independent predictors of LV dysfunction; (3) After ablation, the LV
systolic function could be improved in patients with LVS VA, and (4) PVC
QRS duration and baseline LVEF before ablation were two predictors for
patients with LV function recovery after ablation.
Prevalence and incidence of LV dysfunction in patients with
LVS VA
The prevalence of PVC-induced cardiomyopathy has been reported at 7%
among patients with a PVC burden of more than 10% 24;
however, it is likely underestimated 4. Clinical
studies have reported a diagnosis of PVC-induced cardiomyopathy from 9%
to 30% of patients referred for ablation of PVC 6, 23,
25-27. Nevertheless, most of the previous studies were heterogeneous on
PVC origin, and Yamada et al. reported that PVC-induced cardiomyopathy
in 19.2% of patients referred for ablation of PVC originated from RVOT16. In our study, with all 139 patients, the PVC
originated from LV summit referred for ablation, LV dysfunction was
recognized as 28.8%.
Prediction of LV dysfunction in patients with LVS VA
Most patients with PVC-induced cardiomyopathy have very frequent PVCs;
however, the PVC burden alone does not reliably predict whether
cardiomyopathy will be induced. Baman et al. demonstrated a PVC burden
of 24% best predicted those with and without cardiomyopathy6. Reported cutoff numbers vary from 16% to 26%6, 7, 24; however, PVC-induced cardiomyopathy has been
reported in patients with a PVC burden of only 4% 28,
and normal heart function is often seen in patients with a high PVC
burden. Similarly, in the present study with PVC originating from LV
summit, the mean PVC burden before ablation was 20.6%, and it was not
associated with PVC-induced cardiomyopathy. LV dysfunction could be
found as low as 5% of PVC burden, and normal LV function could be noted
in PVC burden as high as 55% in this large cohort. The result means
that patients’ characteristics and PVC features play more critical roles
in the pathophysiology of PVC-induced cardiomyopathy than PVC burden.
Patients with more prolonged exposure to PVCs or an asymptomatic status
have a higher risk of developing PVC-induced cardiomyopathy in
asymptomatic status 12. Patients without symptoms may
have a higher probability of prolonged exposure to PVCs before they are
disclosed. Of the 139 patients in our study population, only 2 (1.4%)
presented without symptoms, and both had normal LV systolic function.
Because most patients had symptoms, we could not conclude the
association between asymptomatic status and PVC-induced cardiomyopathy
in patients with VA originated from LVS.
PVC QRS duration, with a cut-ff level of >150ms best
separated patients with and without PVC induced cardiomyopathy, reported
by Yokokawa et al 9. QRS duration was still be found
to be the predisposing factor for LV dysfunction from the present
study9. The result was in line with previous studies
with PVCs originating from various locations throughout both ventricles.
The proposed mechanisms included ventricular dyssynchrony,
asymmetrically increased wall thickness, and work overload in the late
activated regions, all contributing to further myocardium remodeling4.
As previously mentioned, most studies focusing on PVC-induced
cardiomyopathy were heterogeneous on PVC origin; however, there were
some reports demonstrated that an epicardial origin was independently
associated with PVC-induced cardiomyopathy 9, 13, 26.
Epicardial PVCs are shown to have longer QRS duration than other PVCs9, maybe due to the paucity of Purkinje fibers in the
epicardium. The initial part of the wavefront progresses slowly through
the myocardial wall until reaching the Purkinje system at the
subendocardium. This slow transmural activation is reflected as the slow
onset of the QRS on the surface electrocardiogram 29and prolonged transmural activation by measuring the AEAD
[epi-endo]. To the best of our knowledge, this is the first study to
demonstrate the relationship between PVC-induced cardiomyopathy and AEAD
[epi-endo], a novel parameter associated with LV dysfunction in
patients with LVS VA, which reflects the depth of intramural foci. The
longer AEAD [epi-endo] might reflect superficial epicardial foci,
resulting in a longer activation time difference between epicardial and
endocardial exit 22. Although we enrolled all patients
with VA originating from LVS, the wider QRS and larger AEAD
[epi-endo] might indicate VA foci close to the epicardial surface,
causing a long transmural activation time and LV dyssynchrony.
Catheter ablation of LVS VA and the induced LV dysfunction
Catheter ablation of PVCs has been reported to have an acute success
rate of 80%-94%, with a complication rate of up to 5.6%30-32. However, the outcomes for catheter ablation of
LVS VAs were diverse and the success rate was lower than the outcomes
for PVC ablation originated other than LVS, ranging from 22% to 100%
for acute procedural success and from 23% to 100% for freedom from VA
recurrences 14, 18, 33, 34. In the present study,
ablation of LVS VAs was effective, with a high acute success rate
(92.8%). Also, in patients with LV dysfunction, the decreased LVEF
improved from 37.5 ± 9.3% to 48.5 ± 10.2% (P <
0.001), indicating the reversible phenomenon of PVC-induced
cardiomyopathy, which was comparable to previous studies showing that
after successful ablation of the PVCs originated from various locations,
there was a mean improvement of LVEF from 10%-15% 13,
26, 31, 35, 36.
In the present study, 50% of patients recovered LV systolic function.
For patients without recovery, we found that longer VA QRS duration and
poorer LVEF before ablation were two independent factors in predicting
irreclaimable LV dysfunction. Our study was in accordance with previous
study 37. Combining with the poor LVEF as another
prediction, the results echoed our postulation that patients with longer
PVC QRS duration may have more severe and irreversible underlying LV
substrate abnormalities, which was an indicator rather than a cause for
LV cardiomyopathy.
Clinical Implications
LVS has been demonstrated to be an essential anatomic focus for the
origin of VA. According to the present study, the incidence of LV
dysfunction in patients with frequent VA from LVS PVC is high (28.8%).
A significant improvement in LV systolic function in patients with LVS
VA-induced cardiomyopathy could be achieved after successful ablation.
The discrepancy of activation (between endocardium and epicardium) and
the QRSd were the only predictors for LV dysfunction; hence, patients
with longer QRS duration should be advocated for an earlier intervention
to eliminate the VA.
Study limitations
There were several limitations for the present study. First, the present
results were obtained from relatively small study samples and
retrospective in nature, besides, no control group was included in the
present study. The prospective, randomized study with large sample size
to validate the results is mandated. Second, we did not collect cardiac
magnetic resonance (CMR) data, and therefore, myocardial fibrosis before
the ablation could not be analyzed and limiting us to detect significant
CMR predictors of the development of PVC induced cardiomyopathy. Third,
the VA duration was proved to be a predictor for VA induced
cardiomyopathy 12, and which was not collected in the
present study.