Premature ventricular contractions in children and young adults: natural history and clinical implications

Background

Premature ventricular contractions (PVCs) are common in children and are typically perceived as benign.¹ However, frequent PVCs have been associated with left ventricular (LV) dysfunction in adults. While this phenomenon is well-described in adults,^2–8 it is less well-defined in children.^9–13 We sought to characterize the natural history of PVCs in childhood including the prevalence of, and factors associated with, LV dysfunction.

Methods

We performed a single-centre retrospective cohort study from 2003 to 2018 including patients aged 1–21 years with frequent PVCs (>0.5% on 24-h Holter monitoring), a 12-lead ECG with ≥1 PVC, and an echocardiogram. Patients with congenital heart disease aside from minor septal defects and valvular abnormalities and those with known personal or family history of primary electrical or cardiomyopathic disease were excluded. This study was approved by our Institutional Review Board.

The primary outcome was LV dysfunction [LV ejection fraction (EF) < 50%]. Logistic regression and Cox proportional hazards were used to investigate the relationship between predictor variables and LV dysfunction at presentation and during follow-up, respectively. In patients with serial Holter monitors prior to initiation of PVC-directed therapy, Wilcoxon signed-rank test was used to assess change in PVC burden. Relationships between continuous variables were investigated using Pearson correlation.

Results

We identified 198 patients with median age 12.3 years [interquartile range (IQR) 7.8–15.8 years] of whom 114 (58%) were male. Median PVC burden was 8.9% (IQR 4.1–15.5%). At presentation, seven patients (4%) had LV dysfunction which was associated with older age, higher PVC burden, longer PVC QRS duration, shorter prematurity index, couplets, triplets, non-sustained ventricular tachycardia (NSVT), and polymorphic PVCs (Table 1). There was no correlation between age and PVC burden [Pearson correlation coefficient (r) = −0.06, P = 0.44), moderate positive correlation between age and PVC QRS duration (r = 0.50, P < 0.001), and moderate negative correlation between age and prematurity index (r = −0.32, P < 0.001).

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.

^aOdds 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 scatterplot displaying LVEF vs. PVC burden is shown in Figure 1A. A PVC burden ≥15% was 100% sensitive and 76% specific for LV dysfunction at time of presentation. Six of the seven patients with LV dysfunction had an LVEF >40%, and one patient with a PVC burden >50% had an LVEF of 31%. Thirty-three patients had a PVC burden between 15.0 and 29.9%, and 3 (9%) of these patients had LV dysfunction. Twenty patients had a PVC burden ≥30%, and 4 (20%) of these patients had LV dysfunction.

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.

Sixty-two patients had longitudinal echocardiographic follow-up (median 3.6 years, IQR 2.2–6.5 years). Four (6%) patients developed LV dysfunction during follow-up (median time to dysfunction 2.3 years, range 0.6–6.1 years), all with LVEF >40%. Left ventricular dysfunction was associated with increased LV end-diastolic volume (LVEDV) z-score at time of initial echocardiogram {hazard ratio 3.5 [95% confidence 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 Holter compared to the last available recording (or last prior to initiation of treatment) decreased from a median of 10.2% (IQR 6.4–16.6%) to 1.8% (0.0–10.9%), (P < 0.001); Figure 1B. Premature ventricular contraction burden decreased by >50% in 67 (58%) patients and decreased to <0.5% in 51 (44%) patients. However, PVC burden increased in 31 (27%) patients. Factors associated with a lack of PVC burden decrease by >50% included older age [odds ratio (OR) 0.55 (95% CI 0.37–0.84) per 5-year increase, P = 0.005] and presence of couplets [OR 0.38 (0.18–0.80), P = 0.011].

Discussion

Here, we report a relatively large cohort of almost 200 young patients with frequent PVCs which provides important insights regarding the natural history and clinical implications of frequent PVCs in this population:

1. Premature ventricular contraction burden decreased significantly over time in most patients with frequent PVCs but increased in a minority.

2. Left ventricular dysfunction was rare but may be present at initial presentation or develop during follow-up.

3. Older age, increased PVC burden, complex ventricular ectopy [(couplets, triplets, NSVT, polymorphic PVCs); CVE], and increased PVC QRS duration were associated with LV dysfunction.

4. Risk of LV dysfunction increases with increasing PVC burden and a threshold of ≥15% best discriminated between patients with and without LV dysfunction at time of presentation in our cohort.

5. Development of LV dysfunction during follow-up may be heralded by LV dilation.

These findings suggest young children with <15% PVCs and no CVE are at very low risk for LV dysfunction and are very likely to have a spontaneous reduction in PVC burden. Our finding of LV dysfunction in patients with PVC burdens as low as 15% contrasts a prior report in which only children with PVC burdens ≥30% had LV dysfunction,⁹ though notably in our study patients with ≥30% PVCs were more than twice as likely to have LV dysfunction as those with 15–29.9% PVCs. Given the low positive predictive value in regard to LV dysfunction secondary to the rarity of LV dysfunction and frequent spontaneous reduction in PVC burden observed in our cohort, especially in younger children without CVE, we do not believe a PVC burden ≥15% alone constitutes an indication for PVC-directed therapy.

Increased PVC burden and CVE have previously been associated with LV dysfunction in children,⁹ while other studies have shown no association between PVC burden and LV dysfunction.^11,13 Older age and increased PVC QRS duration have not previously been reported in association with LV dysfunction in children, though the latter has been in adults,^6,8 and these two variables appear collinear. Unfortunately, we were not able to perform multivariable analyses to better understand these relationships given the rarity of the primary outcome. Patients with elevated LVEDV appear to be at risk for developing LV dysfunction and may benefit from heightened surveillance and/or consideration of intervention.

Our study was limited by its retrospective nature and small number of patients meeting the primary outcome. Additionally, a 24-h monitoring period may not provide an accurate estimation of a patient’s overall ventricular ectopy burden. A prospective multicentre analysis would help better define these relationships.

Funding

NHLBI T32HL007572 to R.P.