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\begin{document}

\title{Risk Factors for Recurrent Ventricular Arrhythmias in Patients with
Idiopathic Ventricular Fibrillation}



\author[1]{Rand Ibrahim}%
\author[1]{Marwan Refaat}%
\affil[1]{American University of Beirut Medical Center}%


\vspace{-1em}



  
  \date{May 24, 2024}


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Sudden Cardiac Death (SCD) remains a global
threat.\textsuperscript{1}The most common causes of SCD are ischemic
heart diseases and structural cardiomyopathies in the elderly.
Additional causes can be arrhythmogenic, respiratory, metabolic, or even
toxigenic.\textsuperscript{2,3,4} Despite the novel diagnostic tools and
our deeper understanding of pathologies and genetic associations, there
remains a subset of patients for whom a trigger is not identifiable.
When associated with a pattern of Ventricular Fibrillation, the
diagnosis of exclusion is deemed Idiopathic Ventricular Fibrillation
(IVF).\textsuperscript{2,5} IVF accounts for 5\% of all
SCDs\textsuperscript{6} -- and up to 23\% in the young male
subgroup\textsuperscript{5} -- and has a high range of recurrence rates
(11-45\%).\textsuperscript{7,8,9} There are still knowledge gaps in the
initial assessment, follow-up approach, risk stratification and
subsequent management for IVF.\textsuperscript{1,10,11} While subsets of
IVF presentations have been better characterized into channelopathies,
such as Brugada's syndrome (BrS), Long QT Syndrome (LQTS), Early
Repolarization Syndrome (ERS), Catecholaminergic Polymorphic Ventricular
Tachycardia (CPVT), much remains to be
discovered.\textsuperscript{12,13} Implantable Cardioverter Device (ICD)
placement as secondary prevention for IVF is the standard of care. This
is warranted in the setting of high recurrence rates of arrhythmias
(11-43\%). Multiple studies have shown potential complications from ICDs
and a significant number of cases experiencing inappropriate shock after
ICD placement.\textsuperscript{14}

In their article, Stampe et al. aim to further understand clinical
presentation and assessment, and risk factors for recurrent ventricular
arrhythmias in IVF patients. Using a single-centered retrospective
study, they followed a total of 84 Danish patients who were initially
diagnosed with IVF and received a secondary ICD placement between
December 2007 and June 2019. Median follow-up time was 5.2 years
(ICR=2-7.6). To ensure detection of many possible underlying etiologies
ranging from structural, ischemic, arrhythmogenic, metabolic, or
toxicologic, the researchers found that a wide array of diagnostic tools
were necessary: standard electrocardiograms (ECGs), high-precordial
leads ECGs, standing ECGs, Holter monitoring, sodium-channel blocker
provocation tests, exercise stress tests, echocardiograms, cardiac
magnetic resonance imaging, coronary angiograms, cardiac computed
tomography, electrophysiological studies, histological assessment, blood
tests, toxicology screens, and genetic analysis.

The study by Stampe et al. highlights the importance of thorough and
continuous follow-up with rigorous evaluation: Three (3.6\%) patients
initially diagnosed with IVF were later found to have underlying cardiac
abnormalities (LQTS and Dilated Cardiomyopathy) that explained their
SCA. Like other studies, the burden of arrhythmia was found to be high,
but unlike reported data, the overall prognosis of IVF was good. Despite
the initial pattern of ventricular fibrillation in those who experienced
appropriate ICD placement (29.6\%), ventricular tachycardia and
ventricular fibrillation had a comparable predominance. As for patients
with inappropriate ICD placements, atrial fibrillation was a commonly
identified pathological rhythm (16.7\%). Recurrent cardiac arrest at
presentation (19.8\%) was a risk factor for appropriate ICD therapy
(HR=2.63, CI=1.08-6.40, p=0.033). However, in contrast to previous
studies, early repolarization detected on baseline ECG (12.5\%), was not
found to be a risk factor (p=0.842).

The study by Stampe et al. has few limitations. First, the study design,
a retrospective cohort, precluded standardized follow-up frequencies and
diagnostic testing. Second, while the study was included many of the
cofounders tested in previous studies (baseline characteristics,
baseline ECG patterns, comorbidities), medication use was not included.
Third, the follow-up period may have been insufficient to detect effect
from some of the confounding factors. Finally, the sample size was small
and it was from a single center.

There are several strengths of the Stampe et al. study. Firstly, the
wide range of diagnostic tests used at index presentation and during the
follow-up period ensured meticulous detection of most underlying
etiologies. Secondly, appropriate and well-defined inclusion and
exclusion criteria were used. Thirdly, funding by independent parties
ensured no influence on study design, result evaluation, and
interpretation. Finally, the study has succeeded in improving our
understanding of IVF. Future studies should include though a larger
population size and a more diverse population.

References:

1.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, et al. Effect
of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on
Appropriate Implantable Cardiac Defibrillator Shock: Insights from the
GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7):
115(7):924-31.

2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS
guideline for management of patients with ventricular arrhythmias and
the prevention of sudden cardiac death: executive summary. J Am Coll
Cardiol 2018;72:e91--e220.

3. Refaat MM, Hotait M, London B: Genetics of Sudden Cardiac Death. Curr
Cardiol Rep Jul 2015; 17(7): 606

4. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al.
HRS/EHRA/APHRS expert consensus statement on the diagnosis and
management of patients with inherited primary arrhythmia syndromes:
document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA,
PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932--1963.

5. Priori SG, Blomstr\selectlanguage{ngerman}öm-Lundqvist C, Mazzanti A, et al. ESC Guidelines
for the management of patients with ventricular arrhythmias and the
prevention of sudden cardiac death: The Task Force for the Management of
Patients with Ventricular Arrhythmias and the Prevention of Sudden
Cardiac Death of the European Society of Cardiology (ESC). Endorsed by:
Association for European Paediatric and Congenital Cardiology (AEPC).
Eur Heart J 2015;36(41):2793-2867.

6. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation.
1998;98:2334--2351.

7. Ozaydin M, Moazzami K, Kalantarian S, Lee H, Mansour M, Ruskin JN.
Long-term outcome of patients with idiopathic ventricular fibrillation:
a meta-analysis. J Cardiovasc Electrophysiol 2015;26:1095--1104.

8. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et
al. Outcome of apparently unexplained cardiac arrest: results from
investigation and follow-up of the prospective cardiac arrest survivors
with preserved ejection fraction registry. Circ Arrhythm Electrophysiol
2016;9:e003619.

9. Siebermair J, Sinner MF, Beckmann BM, Laubender RP, Martens E,
Sattler S, et al.Early repolarization pattern is the strongest predictor
of arrhythmia recurrence in patients with idiopathic ventricular
fibrillation: results from a single centre long-term follow-up over 20
years. Europace 2016;18:718-25.

10. Refaat MM, Hotait M, Tseng ZH: Utility of the Exercise
Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification.
Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.

11. Gray B, Ackerman MJ, Semsarian C, Behr ER. Evaluation after sudden
death in the young: a global approach. Circ Arrhythm Electrophysiol
2019;12: e007453.

12. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et
al. Response to Letter Regarding Article, Outcome of apparently
unexplained cardiac arrest: results from investigation and follow-up of
the prospective cardiac arrest survivors with preserved ejection
fraction registry''. Circ Arrhythm Electrophysiol 2016;9:e004012.

13. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza
D, et al. Genetic basis and molecular mechanism for idiopathic
ventricular fibrillation. Nature 1998;392:293--296.

14. Baranchuk A, Refaat M, Patton KK, Chung M, Krishnan K, et al. What
Should You Know About Cybersecurity For Cardiac Implantable Electronic
Devices? ACC EP Council Perspective. J Am Coll Cardiol Mar 2018;
71(11):1284-1288.

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