Europace (2024) 26, 1–3 RESEARCH LETTER

[Link]

Premature ventricular contractions in children

and young adults: natural history and clinical
implications
Robert Przybylski *†, Omar Meziab †, Kimberlee Gauvreau , Audrey Dionne ,
Elizabeth S. DeWitt, Vassilios J. Bezzerides , and Dominic J. Abrams
Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA

Received 11 January 2024; accepted after revision 10 February 2024; online publish-ahead-of-print 4 March 2024

-Keywords
--------------------------------------------------------------------------------------------------------------------------------------------------------------
PVCs • Paediatric cardiology • PVC cardiomyopathy

PVC burden was 8.9% (IQR 4.1–15.5%). At presentation, seven pa­

Background tients (4%) had LV dysfunction which was associated with older age,
Premature ventricular contractions (PVCs) are common in children and higher PVC burden, longer PVC QRS duration, shorter prematurity in­
are typically perceived as benign.1 However, frequent PVCs have been as­ dex, couplets, triplets, non-sustained ventricular tachycardia (NSVT),
sociated with left ventricular (LV) dysfunction in adults. While this phenom­ and polymorphic PVCs (Table 1). There was no correlation between
enon is well-described in adults,2–8 it is less well-defined in children.9–13 We age and PVC burden [Pearson correlation coefficient (r) = −0.06,
sought to characterize the natural history of PVCs in childhood including P = 0.44), moderate positive correlation between age and PVC QRS
the prevalence of, and factors associated with, LV dysfunction. duration (r = 0.50, P < 0.001), and moderate negative correlation be­
tween age and prematurity index (r = −0.32, P < 0.001).
A scatterplot displaying LVEF vs. PVC burden is shown in Figure 1A. A
Methods PVC burden ≥15% was 100% sensitive and 76% specific for LV dysfunc­
We performed a single-centre retrospective cohort study from 2003 to tion at time of presentation. Six of the seven patients with LV dysfunc­
2018 including patients aged 1–21 years with frequent PVCs (>0.5% on tion had an LVEF >40%, and one patient with a PVC burden >50% had
24-h Holter monitoring), a 12-lead ECG with ≥1 PVC, and an echocardio­ an LVEF of 31%. Thirty-three patients had a PVC burden between 15.0
gram. Patients with congenital heart disease aside from minor septal defects and 29.9%, and 3 (9%) of these patients had LV dysfunction. Twenty pa­
and valvular abnormalities and those with known personal or family history tients had a PVC burden ≥30%, and 4 (20%) of these patients had LV
of primary electrical or cardiomyopathic disease were excluded. This study dysfunction.
was approved by our Institutional Review Board.
Sixty-two patients had longitudinal echocardiographic follow-up
The primary outcome was LV dysfunction [LV ejection fraction (EF) <
50%]. Logistic regression and Cox proportional hazards were used (median 3.6 years, IQR 2.2–6.5 years). Four (6%) patients developed
to investigate the relationship between predictor variables and LV dysfunc­ LV dysfunction during follow-up (median time to dysfunction 2.3 years,
tion at presentation and during follow-up, respectively. In patients with ser­ range 0.6–6.1 years), all with LVEF >40%. Left ventricular dysfunction
ial Holter monitors prior to initiation of PVC-directed therapy, Wilcoxon was associated with increased LV end-diastolic volume (LVEDV)
signed-rank test was used to assess change in PVC burden. Relationships be­ z-score at time of initial echocardiogram {hazard ratio 3.5 [95% confi­
tween continuous variables were investigated using Pearson correlation. dence interval (CI) 1.2–10.7] per 1 unit increase in z-score, P = 0.026}.
Serial Holter monitoring was performed in 116 patients (median
interval 3.2 years, IQR 2.0–5.0 years). PVC burden on the initial
Results Holter compared to the last available recording (or last prior to initi­
We identified 198 patients with median age 12.3 years [interquartile ation of treatment) decreased from a median of 10.2% (IQR 6.4–
range (IQR) 7.8–15.8 years] of whom 114 (58%) were male. Median 16.6%) to 1.8% (0.0–10.9%), (P < 0.001); Figure 1B. Premature

* Corresponding author. Tel: +1 703 573 0504. E-mail address: [Link]@[Link]

†
Co-first authors.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ([Link] which permits
non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [Link]@[Link]
2 R. Przybylski et al.

Table 1 Univariable analysis for factors associated with LV dysfunction (LVEF <50%) at time of presentation

No LV dysfunction (n = 191) LV dysfunction (n = 7) OR [95% CI] P-value

..............................................................................................................................................
Demographics
Male sex 108 (57) 6 (86) 4.6 [0.5–39.0] 0.161
Age 12.1 (7.8–15.6) 17.6 (16.2–17.6) 4.5 [1.25–16.1] per 5-year increase 0.021
Congenital heart disease 8 (4) 1 (14) 3.8 [0.4–35.5] 0.240
Presentation
PVCs incidentally noted 140 (73) 6 (86) 2.2 [0.3–18.6] 0.474
Initial Holter results
PVC burden (%) 8.6 (3.9–14.9) 33.6 (18.5–36.8) 1.6 [1.3–2.2] per 5% increase <0.001
Sustained VT 3 (2) 1 (14) 10.4 [0.9–115.7] 0.056
Non-sustained VT 11 (6) 4 (57) 21.8 [4.3–109.8] <0.001
Coupletsa 73 (38) 7 (100) a
0.001
Triplets 26 (14) 4 (57) 8.5 [1.8–40.0] 0.007
Polymorphic PVCs 9 (5) 2 (29) 8.1 [1.4–47.5] 0.021
ECG PVC characteristics
Inferior QRS axis 156 (82) 6 (86) 1.3 [0.2–11.5] 0.786
LBBB morphology 141 (74) 5 (71) 0.9 [0.2–4.7] 0.888
Outflow tract morphology 118 (62) 5 (71) 1.5 [0.3–8.2] 0.608
PVC coupling interval (ms) 477 (420–531) 467 (399–497) 0.9 [0.7–1.1] per 25 ms increase 0.420
Prematurity index 0.64 (0.56–0.75) 0.50 (0.47–0.54) 0.2 [0.1–0.6] per 0.1 increase 0.006
PVC QRS duration (ms) 135 (119–151) 160 (157–168) 4.0 [1.5–10.9] per 25 ms increase 0.007
Maximum deflection index 0.43 (0.34–0.53) 0.41 (0.28–0.44) 0.6 [0.3–1.3] per 0.1 increase 0.197

CI, confidence interval; LBBB, left bundle branch block; LV, left ventricular; OR, odds ratio; PVC, premature ventricular contraction; VT, ventricular tachycardia.
a
Odds ratio cannot be estimated because all patients with LV dysfunction are in one group; P-values are estimated from logistic regression analysis and bolded values represent statistically
significant p-values.

A B
80 60

50 P < 0.001
60
40
LV EF (%)

PVCs (%)

40 30

20
20
10

0 0
0 10 20 30 40 50 60 Initial holter Last holter
PVCs (%)

Figure 1 (A) Scatter plot of LVEF vs. PVC burden at presentation. (B) Change in PVC burden from first to last Holter monitor in patients with serial
Holter monitors. LVEF, left ventricular ejection fraction; PVC, premature ventricular contraction.

ventricular contraction burden decreased by >50% in 67 (58%) pa­ of PVC burden decrease by >50% included older age [odds ratio
tients and decreased to <0.5% in 51 (44%) patients. However, PVC (OR) 0.55 (95% CI 0.37–0.84) per 5-year increase, P = 0.005] and pres­
burden increased in 31 (27%) patients. Factors associated with a lack ence of couplets [OR 0.38 (0.18–0.80), P = 0.011].
Frequent PVCs and ventricular function in children 3

Discussion ventricular ectopy burden. A prospective multicentre analysis would

help better define these relationships.
Here, we report a relatively large cohort of almost 200 young patients
with frequent PVCs which provides important insights regarding the Funding
natural history and clinical implications of frequent PVCs in this NHLBI T32HL007572 to R.P.
population:
Conflict of interest: none declared.
(1) Premature ventricular contraction burden decreased significantly
over time in most patients with frequent PVCs but increased in a
minority. References
(2) Left ventricular dysfunction was rare but may be present at initial 1. Tsuji A, Nagashima M, Hasegawa S, Nagai N, Nishibata K, Goto M et al. Long-term
presentation or develop during follow-up. follow-up of idiopathic ventricular arrhythmias in otherwise normal children. Jpn Circ
(3) Older age, increased PVC burden, complex ventricular ectopy [(cou­ J 1995;59:654–62.
plets, triplets, NSVT, polymorphic PVCs); CVE], and increased PVC 2. Voskoboinik A, Hadjis A, Alhede C, Park H, Moss J, Marcus GM et al. Predictors of ad­
QRS duration were associated with LV dysfunction. verse outcome in patients with frequent premature ventricular complexes: the ABC-VT
(4) Risk of LV dysfunction increases with increasing PVC burden and a risk score. Heart Rhythm 2020;17:1066–74.
threshold of ≥15% best discriminated between patients with and 3. Ban JE, Park HC, Park JS, Nagamoto Y, Choi JI, Lim HE et al. Electrocardiographic and
without LV dysfunction at time of presentation in our cohort. electrophysiological characteristics of premature ventricular complexes associated with
(5) Development of LV dysfunction during follow-up may be heralded by left ventricular dysfunction in patients without structural heart disease. Europace 2013;
LV dilation. 15:735–41.
4. Baman TS, Lange DC, Ilg KJ, Gupta SK, Liu TY, Alguire C et al. Relationship between
These findings suggest young children with <15% PVCs and no CVE burden of premature ventricular complexes and left ventricular function. Heart
are at very low risk for LV dysfunction and are very likely to have a Rhythm 2010;7:865–9.
spontaneous reduction in PVC burden. Our finding of LV dysfunction 5. Hasdemir C, Ulucan C, Yavuzgil O, Yuksel A, Kartal Y, Simsek E et al.
in patients with PVC burdens as low as 15% contrasts a prior report Tachycardia-induced cardiomyopathy in patients with idiopathic ventricular arrhyth­
mias: the incidence, clinical and electrophysiologic characteristics, and the predictors.
in which only children with PVC burdens ≥30% had LV dysfunction,9 J Cardiovasc Electrophysiol 2011;22:663–8.
though notably in our study patients with ≥30% PVCs were more 6. Del Carpio Munoz F, Syed FF, Noheria A, Cha YM, Friedman PA, Hammill SC et al.
than twice as likely to have LV dysfunction as those with 15–29.9% Characteristics of premature ventricular complexes as correlates of reduced left ven­
PVCs. Given the low positive predictive value in regard to LV dysfunc­ tricular systolic function: study of the burden, duration, coupling interval, morphology
tion secondary to the rarity of LV dysfunction and frequent spontan­ and site of origin of PVCs. J Cardiovasc Electrophysiol 2011;22:791–8.
eous reduction in PVC burden observed in our cohort, especially in 7. Yokokawa M, Kim HM, Good E, Crawford T, Chugh A, Pelosi F et al. Impact of QRS
duration of frequent premature ventricular complexes on the development of cardio­
younger children without CVE, we do not believe a PVC burden myopathy. Heart Rhythm 2012;9:1460–4.
≥15% alone constitutes an indication for PVC-directed therapy. 8. Moulton KP, Medcalf T, Lazzara R. Premature ventricular complex
Increased PVC burden and CVE have previously been associated morphology. A marker for left ventricular structure and function. Circulation 1990;81:
with LV dysfunction in children,9 while other studies have shown no as­ 1245–51.
sociation between PVC burden and LV dysfunction.11,13 Older age and 9. Bertels RA, Harteveld LM, Filippini LH, Clur SA, Blom NA. Left ventricular dysfunction is
increased PVC QRS duration have not previously been reported in as­ associated with frequent premature ventricular complexes and asymptomatic ventricu­
lar tachycardia in children. Europace 2017;19:617–21.
sociation with LV dysfunction in children, though the latter has been in 10. Abadir S, Blanchet C, Fournier A, Mawad W, Shohoudi A, Dahdah N et al.
adults,6,8 and these two variables appear collinear. Unfortunately, we Characteristics of premature ventricular contractions in healthy children and their im­
were not able to perform multivariable analyses to better understand pact on left ventricular function. Heart Rhythm 2016;13:2144–8.
these relationships given the rarity of the primary outcome. Patients 11. Guerrier K, Anderson JB, Czosek RJ, Mays WA, Statile C, Knilans TK et al. Usefulness of
with elevated LVEDV appear to be at risk for developing LV dysfunction ventricular premature complexes in asymptomatic patients ≤21 years as predictors of
and may benefit from heightened surveillance and/or consideration of poor left ventricular function. Am J Cardiol 2015;115:652–5.
12. Spector ZZ, Seslar SP. Premature ventricular contraction-induced cardiomyopathy in
intervention. children. Cardiol Young 2016;26:711–7.
Our study was limited by its retrospective nature and small number 13. Sharma N, Cortez D, Imundo JR. High burden of premature ventricular contractions in
of patients meeting the primary outcome. Additionally, a 24-h monitor­ structurally normal hearts: to worry or not in pediatric patients? Ann Noninvasive
ing period may not provide an accurate estimation of a patient’s overall Electrocardiol 2019;24:e12663.