Impact of Atrial Pacing in Fontan Patients with Junctional Rhythm: A Prospective Echocardiographic Study

doi:10.21203/rs.3.rs-3117820/v1

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Impact of Atrial Pacing in Fontan Patients with Junctional Rhythm: A Prospective Echocardiographic Study

https://doi.org/10.21203/rs.3.rs-3117820/v1

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published 07 Dec, 2023

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BACKGROUND

Sinus node dysfunction (SND) with junctional rhythm (JR) is common after the Fontan operation. Atrial pacing (AP) restores atrioventricular (AV) synchrony, but the placement of a pacemaker carries significant morbidity.

OBJECTIVES

To study the impact of AP on echocardiographic parameters of function in Fontan patients with SND and JR.

METHODS

Nine Fontan patients with AP for SND and JR were prospectively studied with echocardiography in the following conditions – baseline paced rhythm, underlying JR and, if possible, slow-paced rhythm below their baseline paced rate (~ 10 bpm faster than their JR rate).

RESULTS

Cardiac index was significantly lower in JR (3 ± 1.1 L/min/m2) vs AP (4.2 ± 1.4 L/min/m2; p = 0.002). Diastolic function also significantly worsened with increased ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e’ ratio) by tissue Doppler imaging (TDI) in JR (11.6 ± 4.6) vs AP (8.8 ± 2.2, p = 0.016). Pulmonary venous flow reversal was present in 0/9 patients in AP and 7/9 in JR (p = 0.016). There were no significant differences in these echocardiographic measurements between the paced and slow-paced conditions.

CONCLUSIONS

When compared to AP, JR was associated with a significant reduction in cardiac output and diastolic function, and an increased prevalence of pulmonary vein flow reversal. There were no differences between paced and slow-paced conditions, suggesting that AV synchrony rather than heart rate was primarily contributing to cardiac output. Further studies are needed to understand the chronic impact of JR on Fontan outcomes.

echocardiography

single ventricle

sinus node dysfunction

junctional rhythm

atrial pacemaker

First introduced in 1971, the Fontan operation has transformed the management and outcomes of single ventricle patients. Even in his initial papers, Fontan stressed the importance of sinus rhythm in these patients as a key to optimal outcomes.¹ Cardiac rhythm abnormalities can significantly alter the efficiency of the Fontan circuit, thus impacting the functional status and outcomes in patients who have had the Fontan operation.²

Specifically, a significant number of Fontan patients develop sinus node dysfunction (SND) following the operation with published prevalence ranging from 11–44%.^3–5 The development of SND is attributed to either surgical damage to the sinus node or its arterial supply at the time of surgery, atrial dilation or elevated atrial pressures.² It has also been speculated that genetics, neonatal cardiopulmonary bypass and cyanosis with secondary injury to and fibrosis of the myocardium and conduction system plays a role in the genesis of SND.² Patients with SND typically default to an escape junctional rhythm (JR) with resultant loss of atrioventricular (AV) synchrony. Sinus node dysfunction can present immediately after the procedure, or as a late consequence with an ongoing risk for development of loss of sinus rhythm during follow up.^3,6,7 It additionally has been shown that the development of arrhythmias, both tachyarrhythmias and bradyarrhythmias, is a sign of poor future prognosis.⁸

Patients with significant SND and JR sometimes undergo placement of a permanent pacemaker,⁹ based on individual physician preference, though the clinical benefits of restoring AV synchrony by way of atrial pacing (AP) in Fontan patients with an adequate escape JR remains unclear. Studies investigating the impact of pacing on the outcomes in Fontan patients have yielded conflicting results. Early studies have suggested improved outcomes with pacing,^9,10 while more recent studies have suggested significantly increased adverse consequences with presence of a pacemaker in Fontan patients.^11–15

While the long-term benefits of AP for SND in patients with the Fontan operation is yet to be demonstrated, there are catheter-based studies that have demonstrated hemodynamic benefit with AP as illustrated by improved cardiac output, left atrial pressure and central venous pressure.^16–18 Echocardiographic metrics of cardiac systolic and diastolic function in patients with SND and Fontan physiology has not yet been studied. We sought to study the echocardiographic impact of JR and AP on cardiac function in Fontan patients.

Between January 2022 and January 2023, we performed a prospective single-center cohort study of pediatric Fontan patients followed at our institution with a previously implanted AP for SND and escape JR. This study was approved by the Institutional Review Board (IRB) at Oregon Health and Science University. An IRB approved parent consent, in addition to patient assent, was obtained for all study subjects.

Inclusion criteria included all children, regardless of original anatomy, who were status post Fontan operation and permanent AP placement for SND with an escape JR. While none of the following exclusion criteria were found in our study population, they included underlying JR < 40 beats per minute (bpm), rhythm requiring ventricular pacing, clinical evidence of heart failure, or development of shortness of breath or dizziness while in their underlying JR.

Enrolled subjects underwent an extended echocardiogram performed in two (and, if possible, three) possible physiologic conditions. The first condition was the patient’s baseline condition, which consisted of AP in all, unaltered from how the subject entered the lab. After the initial images were obtained, the pacemaker’s rate was gradually decreased until their underlying escape JR was noted. This represented the second condition. The final condition was at a slow-paced rhythm at 10 pm above their underlying JR rate. If the rate of their escape JR was < 10 bpm slower than their baseline paced rhythm, then this third condition was omitted. There was a five-minute observation period following pacemaker alterations to the imaging protocol, to allow for some degree of equilibration in each physiologic state.

For each subject, demographic data and surgical history was extracted from their electronic medical record. Echocardiographic measurements were obtained within syngo Dynamics (Siemens Healthcare, Erlangen, Germany), and many of the estimations of function were performed using the program’s internal calculators. Echocardiographic parameters assessed for each patient for each phase are outlined in Table 1. Statistical evaluation of differences in continuous variables between phases was performed with paired T-tests, and for binomial variables with the McNemar test. Statistical significance was defined as a significance level of 0.05.

Table 1

Echocardiogram study protocol.
Shortening fraction (%)
Ejection fraction (%) by 5/6 area-length and Simpson’s 4-chamber area change
Cardiac output (L/min)
Cardiac index (L/min/m²)
Indexed stroke volume (mL/m²)
Myocardial performance index
dP/dT (mmHg/sec)
TDI E/e’ ratio
TAPSE
Fenestration patency
Aortic valve regurgitation
Pulmonary vein reversal
Hepatic vein filling fraction
IVC collapsibility (%)
dP/dT: ratio of pressure change during isovolumetric contraction; E/e’ ratio, ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity; IVC: inferior vena cava; TAPSE: tricuspid annular plane systolic excursion; TDI, tissue Doppler imaging.

Nine patients met the study criteria. Four of whom identified as male, and five as female. The age of the participants ranged from 4 to 18 years, with an average age of 12.8 ± 4.9 years. The anatomic make-up of the cohort included four systemic right ventricles and five systemic left ventricles, specifically hypoplastic left heart syndrome (n = 2), pulmonary atresia with intact ventricular septum (n = 2), tricuspid atresia (n = 2), unbalanced right-dominant atrioventricular septal defect (n = 2), and complex heterotaxy with a hypoplastic left ventricle (n = 1) (Table 2). All of the study patients had undergone an extracardiac conduit Fontan operation.

Table 2

Patient demographics.
Patient	Age (years)	Sex	BSA (m²)	Cardiac pathology	Fenestration (yes/no)	Baseline paced rate (bpm)	Underlying JR rate (bpm)	Slow paced rate (bpm)
1	6	Female	0.7	Right dominant AV canal defect	Y	90	85
2	12	Female	1.87	Hypoplastic left heart syndrome	Y	80	60	70
3	16	Male	1.69	DORV, crisscross AV connections, pulmonary valve stenosis, L-malposed great arteries	N	80	60	70
4	18	Female	1.39	Hypoplastic left heart syndrome	N	75	70
5	17	Male	1.51	Pulmonary atresia with intact ventricular septum	N	80	50	60
6	12	Female	1.78	Pulmonary atresia with intact ventricular septum	N	90	60	70
7	14	Male	1.74	Tricuspid atresia	N	80	70
8	16	Male	1.67	Right dominant AV canal defect	N	80	60	70
9	4	Male	0.46	Tricuspid atresia	Y	80	80
AV: atrioventricular; bpm: beats per minute; BSA: body surface area; DORV: double outlet right ventricle; JR: junctional rhythm.

When compared to their baseline AP rhythm, subjects had a significant decrease in the cardiac index from 4.2 ± 1.4 L/min/m2 to 3.0 ± 1.1 L/min/m2 when in their underlying JR (p = 0.002) (Fig. 1). There was also a significant increase in the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e’ ratio) by tissue Doppler imaging (TDI) from 8.8 ± 2.2 to 11.6 ± 4.6 while in the baseline paced rhythm and underlying JR, respectively (p = 0.016) (Fig. 2). Pulmonary venous flow reversal was observed by Doppler in 0/9 patients when in their baseline paced rhythm, versus 7/9 patients in their underlying JR (p = 0.016). The statistically significant echocardiographic data is summarized in Table 3 (all raw data can be found in the online supplementary material).

Table 3

Statistically significant echocardiographic data in baseline paced and underlying junction rate.
Patient	CI - baseline paced (L/min/m²)	CI - underlying JR (L/min/m²)	EF 5/6 area-length - baseline paced (%)	EF 5/6 area-length - underlying JR (%)	TDI E/e’ ratio - baseline paced	TDI E/e’ ratio - underlying JR	PV flow reversal - baseline paced (yes/no)	PV flow reversal - underlying JR (yes/no)
1	4.3	1.4	48	31	12.7	17.2	N	Y
2	3.4	2.6	48	52	10.2	18.5	N	Y
3	3.4	3.3	41	43	7.6	7.3	N	N
4	4.4	3.5	50	30	11.1	13.2	N	N
5	6.3	3.9	49	49	8.5	9.9	N	Y
6	3.4	2.4	52	50	7.5		N	Y
7	3.3	2.2	54	49	5.6	5.4	N	Y
8	2.6	2.4	48	39	9.3	12.1	N	Y
9	6.5	5.0	54	59	6.7	9.0	N	Y
Mean ± Std Dev	4.2 ± 1.4	3.0 ± 1.1	48.7 ± 4.0	42.9 ± 8.7	8.8 ± 2.2	11.6 ± 4.6	0/9	7/9
p-value		0.002		0.079		0.016		0.016
CI: cardiac index; E/e’ ratio, ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity; EF: ejection fraction; JR: junctional rhythm; PV: pulmonary vein; TDI, tissue Doppler imaging.

While there was notable change in the cardiac index, the ejection and shortening fractions were unchanged. By the 5/6 area-length method, the ejection fraction changed from 48.7 ± 4.0% to 42.9 ± 8.7% between the baseline paced and underlying JR (p = 0.079). By the Simpson’s 4-chamber area change method, the ejection fraction changed from 51.6 ± 5.9% to 45.4 ± 5.2% between the two conditions (p = 0.068). The shortening fraction went from 25.7 ± 5.6% to 24.4 ± 8.0% (p = 0.183). There were no statistically significant differences in any measurement between the baseline AP and slow AP conditions.

This study demonstrated that JR was associated with a significant reduction in cardiac output and diastolic function, as well as an increased prevalence of pulmonary vein flow reversal, in Fontan patients when compared to the same individuals in an AP rhythm. It also highlighted that electrical changes may inhibit the downstream passive draw of blood through the pulmonary vasculature and thus impair the physiologic performance of the Fontan circulation.

We demonstrated that JR in Fontan patients results in a significant reduction in cardiac output which improves with AP. There were no differences between the systolic function, as measured by ejection fraction and shortening fraction. There are key differences in the relative contribution played by preload and ventricular function towards cardiac output in Fontan patients compared to those with a biventricular heart. In Fontan patients, cardiac output is not significantly affected by modest perturbations in contractility, as long as their ventricular function remains reasonable.^19–21 This is likely secondary to the bottleneck effect where cardiac output is more directly driven by flow through the pulmonary circulation due to the absence of a sub-pulmonary ventricle.^19–21 Rychik et al demonstrated that pulmonary venous return in the Fontan patient occurs during ventricular systole. As such, AV valve closure with an incompletely emptied atrium, as seen in AV dyssynchrony, can significantly impair pulmonary venous return in such patients.²² These elements combine to create a situation in JR of impaired ventricular preload and, thereby, cardiac output.

Junctional rhythm was also associated with diastolic dysfunction which was improved by AP, as evaluated by the TDI-derived E/e’ ratio. Mechanistically, it has been hypothesized that decreased cardiac output in the univentricular heart, as seen in these patients when in JR, results in compensatory arterial vasoconstriction which in turn increases the ventricular filling pressure.¹⁹ In addition, this finding may be due to the fact that the loss of AV synchrony in JR will also alter potentially all three phases of atrial function: the reservoir, conduit, and contractile phases of atrial function.²³ This finding is validated by the pulmonary vein flow reversal results of this study. Atrial function impairment would thus impact the rapid filling phase of ventricular preload which is quantified by the AV valve E-wave velocity.

Significant flow reversal in the pulmonary vein was demonstrated, which reflects an increase in left atrial pressure. This may be secondary to the atrium contracting against a closed AV valve during atrial systole (if retrograde conduction is present) or displacement of the closed AV valve into the atrial volume during ventricular systole. Left atrial hypertension, as indicated by pulmonary vein reversal, translates into the systemic venous system, which in turn impedes systemic venous return and thus cardiac preload. Pulmonary vein flow reversal and increased left atrial pressure could also be related to the relative increase in ventricular end-diastolic pressures. Previous reports have shown reversal of flow across the Fontan fenestration,²⁴ as well as retrograde flow through the whole Fontan system as illustrated by cardiac magnetic resonance imaging.²⁵ In this study, while only three patients had patent fenestrations (which prohibited statistically significant conclusions) flow reversal in the fenestration was noted in two patients.

There were no differences seen when comparing the baseline paced and slow-paced conditions. This further supports the notion that AV synchrony, rather than heart rate, was the main contributor to the observed increase in cardiac output. The concept that heart rate does not significantly impact cardiac output in patients with Fontan physiology has previously been described.^{19,21,26−27} While an initial rise in heart rate may increase stroke volume in Fontan patients, this is limited by the bottleneck upstream of the left atrium which results in an absence of preload reserve with which the heart can augment the stroke volume.

This study was limited by the small number of subjects and the heterogeneity of the study population. Additionally, four of the nine subjects had underlying escape JR rates that prohibited evaluation in a slow-paced condition.

Junctional rhythm is associated with a significant impairment of echocardiographic metrics of cardiac output in patients with Fontan circulation which was improved with AP. The impact of JR on cardiac output seems to be primarily due to the loss of AV synchrony with worsened diastolic function and increased left atrial pressures, rather than diminished ventricular function as measured by EF. While this study shows the short-term impact of AP in patients with JR, the longer-term impact of JR and AP needs further investigation. Studies on larger cohorts are also needed to confirm these findings.

AP, atrial pacing, atrial paced and atrial pacemaker;

AV, atrioventricular;

bpm, beats per minute;

E/e’ ratio, ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity;

IRB, Institutional Review Board;

JR, junctional rhythm;

SND, sinus node dysfunction;

TDI, tissue Doppler imaging.

No funding was received for this manuscript. None of the authors have a relationship with industry-relevant to this manuscript. Seshadri Balaji has a research grant from Medtronic to study sudden cardiac death in hypertrophic cardiomyopathy and is a consultant for Milestone Pharmaceuticals. The other authors have no disclosures.

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No competing interests reported.

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You are reading this latest preprint version

Impact of Atrial Pacing in Fontan Patients with Junctional Rhythm: A Prospective Echocardiographic Study

Status:

Journal Publication

Version 1

Abstract

BACKGROUND

OBJECTIVES

METHODS

RESULTS

CONCLUSIONS

Figures

INTRODUCTION

METHODS

RESULTS

DISCUSSION

CONCLUSIONS

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1

Impact of Atrial Pacing in Fontan Patients with Junctional Rhythm: A Prospective Echocardiographic Study

Status:

Journal Publication

Version 1

Abstract

BACKGROUND

OBJECTIVES

METHODS

RESULTS

CONCLUSIONS

Figures

INTRODUCTION

METHODS

RESULTS

DISCUSSION

CONCLUSIONS

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1

Impact of Atrial Pacing in Fontan Patients with Junctional Rhythm: A Prospective Echocardiographic Study