The role of the sympathetic nervous system in the genesis and
perpetuation of ventricular arrhythmias is well recognized. Cardiac
sympathetic denervation (CSD) has been shown to benefit patients with
recurrent ventricular tachycardia (VT) who failed conventional therapy
regardless of the underlying etiology1. Despite this,
CSD is currently utilized as a last option after failing drugs and
catheter ablation. Lack of randomized data on outcomes, short term
follow up in the published literature, cross-cultural nature of the
intervention, misconceptions of the effects on ventricular function in
the setting of advanced structural disease are some of the reasons for
this underutilization. A whole another question is the durability of the
effect. Most studies published so far have had limited follow up and
whether CSD is a one-time effect or not is unknown.
In this issue of JCE, Barwad and colleagues 4investigated the long-term outcomes of 65 patients who underwent CSD due
to refractory ventricular arrhythmias from 2010 to 2019 (reference).
Most patients were men (77%), and the mean age was 50 +/- 18yo. In a
study comprising mostly patients with structural heart disease (SHD),
the authors reported a 92% reduction in shock burden (median 16 [IQR
11-25) to 0 [IQR 0-2] shocks) over a median follow-up of 20 months
(IQR 12 – 36 months). Further, forty-five (69.2%) patients were
rendered free of shocks at two years. To our knowledge, this is one of
the largest studies to assess a more extended follow-up duration in
patients with SHD.
This study shed some light on a critical issue: the sustainability of
the anti-arrhythmic effects of CSD in the long run. The development of
compensatory adrenergic activation, nerve regrowth, and disease
progression are time-dependent variables, and whether they may
compromise CSD benefits later in the follow-up is yet to be determined.
Over a median follow-up of 20 months, the authors found that over 2/3rds
of patients remained shock-free. Such results suggest sustained
anti-arrhythmic properties long after the procedure, even when
considering all the unassessed factors in question. However, due to data
availability limitations, arrhythmic outcomes were given only by shock
recurrence. Sustained VT episodes requiring other types of therapies,
such as anti-tachycardia pacing or chemical cardioversion were not
included in the analyses, and may have contributed to overestimating the
overall benefit. Along the same lines, it is not clear whether the
comparison between the number of shocks before and after the procedure
involved similar time windows. Nevertheless, all these considerations
collectively do not outshine the importance of Barwad and colleagues’
findings, as almost ¾ of patients achieved a lasting shock burden
reduction following CSD. Additionally, consistent with existing data,
the underlying etiology did not predict arrhythmic outcomes, and the
presence of Class III-IV heart failure was associated with a worse
prognosis.
Most patients (92.3%) enrolled in the study underwent bilateral CSD.
Although the systematic use of bilateral CSD (BCSD) is still debatable,
prior reports suggest a superior anti-arrhythmic profile of BCSD
compared to left-only CSD.1 In a recent systematic
review including 173 patients with SHD who underwent CSD, Shah and
colleagues described 82% of the procedures as bilateral. This is in
consonance with our own experience, wherein BCSD has been employed as
the preferred technique.
The study has some limitations. Most patients (79%) underwent CSD
without a prior VT ablation attempt. Despite the author’s arguments on
cost-effectiveness of ablation and VT recurrence rates, we believe that
some points should be carefully pondered before advocating one strategy
over the other. We must recognize that VT ablation holds an overall
safer profile than surgical sympathectomy, even when considering
epicardial procedures. In turn, epicardial ablations have dramatically
contributed to improved catheter ablation (CA) outcomes in patients with
complex substrates 2,3. Both strategies, CSD and CA,
work synergically in refractory cases, but whether CSD yields superior
arrhythmic outcomes enough to disregard the benefits derived from a
stepwise approach, from the less to the most invasive intervention, has
not been yet assessed. Further, it is fair to consider that, although
patients who failed CA seem to benefit from CSD, most patients
undergoing CA do not require adjunctive denervation. On the other hand,
we do acknowledge that there is no strong reason to delay adjunctive
sympathetic denervation in those patients who failed to respond to
standard care. In our institution, we have a low threshold to perform
CSD in eligible patients with refractory VT.
Another important take by the authors resides in the methodology. All
shocks occurring within a 2-week blanking period immediately after CSD
were disregarded as to account for the residual circulation of
neurotransmitters after the procedure. Despite the lack of definitive
information on the exact duration of such vulnerability window, VT
recurrence early after CSD is not a synonym of procedural failure and
may not predict worse late arrhythmic outcomes.
Barwad and colleagues also assessed the long-term hemodynamic impact of
CSD in patients with SHD. The acute and chronic effects of CSD on
cardiovascular performance have been evaluated randomly and thereby
remain a source of concern in this specific population. With a mean left
ventricular ejection fraction (LVEF) of 0.28 +/- 0.13, Barwad and
colleagues showed that LVEF alone was not associated with worse
arrhythmic outcomes. More importantly, LVEF remained stable one year
after CSD. Nevertheless, although these findings corroborate to
demystify low LVEF as a limitation to CSD, further consideration is
necessary while individually weighing the net benefit against the risks.
Five patients in the cohort died from progressive pump failure, and the
presence of advanced heart failure (Class III and IV) was associated
with lower survival rates from shock or death (combined endpoint).
Finally, we congratulate the authors for the outstanding work on some of
the missing CSD puzzle pieces. Evidence of long-term sustained
anti-arrhythmic effects and preserved cardiac function after CSD
contribute to support the expanding role of SCD in the management of
patients with complex arrhythmias. Nonetheless, additional research is
still warranted to optimize patient selection and the optimal timing.