Abstract
Background
Double outlet right ventricle (DORV) encompasses a range of congenital heart defects. Although survival to adulthood has improved, late risks, particularly life-threatening arrhythmias and sudden cardiac death (SCD) persist.
Objectives
We evaluated long-term outcomes in an adult DORV cohort, including SCD risk and device therapy.
Methods
This multicentre, retrospective cohort study enrolled adults with DORV under follow-up at two UK tertiary centres from 2000 to 2023. Patients were classified by anatomical subtype and surgical strategy. The primary composite outcome was all-cause mortality, heart or heart–lung transplantation, aborted SCD or appropriate implantable cardioverter-defibrillator (ICD) shock.
Results
Among 254 patients (median age 20 (IQR 17.6 to 29.2) years; 52.8% male), 61.4% had biventricular repair. Complex (n=90, 35.4%) and Fallot-type (n=79, 31.1%) DORV predominated. Over a median 12.4 (7.4 to 17.3) years, 47 (18.5%) patients died: heart failure (40.4%) and SCD (25.5%) were leading causes. Aborted SCD occurred in 4 (1.6%) cases, 4 (1.6%) underwent heart transplantation and 10 (4.0%) received appropriate ICD shocks. One in eight patients experienced ventricular tachycardia and one in three developed supraventricular tachycardia. In exploratory multivariable analysis restricted to patients with biventricular repair, older age, pulmonary hypertension and baseline QRS >180 ms were associated with the composite outcome.
Conclusions
Amongst adult survivors of DORV, late mortality due to heart failure and SCD was considerable, whereas transplantation was uncommon. In the biventricular-repair subgroup, older age, baseline QRS >180 ms and pulmonary hypertension were associated with adverse outcome in exploratory analysis; these findings require validation.
Keywords: Heart Defects, Congenital; Death, Sudden, Cardiac; Arrhythmias, Cardiac; Heart Failure
WHAT IS ALREADY KNOWN ON THIS TOPIC.
WHAT THIS STUDY ADDS
In this multicentre adult cohort, nearly one-quarter experienced death, transplantation, aborted sudden cardiac death or appropriate implantable cardioverter-defibrillator (ICD) shock; heart failure and sudden death were prominent. Older age, pulmonary hypertension and QRS duration >180 ms were associated with adverse outcomes in exploratory analysis restricted to patients with biventricular repair.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
These findings support lifelong specialist surveillance and further evaluation of potential risk markers; they do not establish indications for primary-prevention ICD implantation.
Introduction
Double outlet right ventricle (DORV) describes a ventriculo-arterial connection in which both great arteries arise predominantly or entirely from the right ventricle.1 The spectrum of congenital heart defects associated with DORV is very broad, ranging from simple anatomical defects, such as ventricular septal defect (VSD), to functionally univentricular hearts. Several associated cardiac anomalies may be present, contributing to the complexity and the heterogeneity of the clinical presentation, diagnosis, classification and management of patients with DORV.
The development of new diagnostic modalities and the evolution of surgical techniques have improved survival in DORV, especially in patients eligible for biventricular surgical repair.2 However, late mortality remains high, even after surgical repair.3–6 Additionally, the risk of sudden cardiac death (SCD) was highlighted by investigators in the early surgical era,5 7 but this finding has not been reproduced in more recent studies reporting the rate of late SCD.2 3 6 Robust data on the incidence of adverse events in adult survivors with DORV are lacking, and there are no established markers of adverse outcome in this population as opposed, for example, to tetralogy of Fallot (ToF), a cardiac anomaly which shares similar anatomical features with a subcategory of DORV.
We assessed the outcome of adults born with various types of DORV, in terms of survival and arrhythmia complications, with particular focus on SCD. We also aimed to identify predictors of long-term adverse outcome from demographic and clinical characteristics, including surface ECG parameters such as QRS duration.
Methods
Patient population
This retrospective multicentre study included all adults with DORV followed at two UK adult congenital heart disease (ACHD) centres between January 2000 and January 2023. Patients were identified from electronic databases; demographic, anatomical, operative, electrocardiographic and arrhythmic data were obtained from clinical records, and mortality data from local databases linked to the Office for National Statistics. Patients whose only available encounter was an initial adult assessment without a subsequent documented follow-up assessment were excluded, as were those whose operative history was insufficient to permit anatomical or surgical classification. Patient-level data are not publicly available because of reidentification risk. There was no patient or public involvement in the study design.
Patients were classified into five anatomical groups, modified from the Congenital Heart Surgery Nomenclature and Database Project: VSD-type, ToF-type, Transposition of the great arteries (TGA)-type with pulmonary stenosis, TGA-type without pulmonary stenosis and complex DORV (remote/non-committed VSD, functionally univentricular hearts or anatomy/physiology precluding repair; figure 1).1 8 Initial anatomy was verified by detailed case-note review, including paediatric operative records.
Figure 1. Clinical classification of DORV, based on amenability to biventricular repair (A vs B), presence of ventriculo-arterial concordance and/or (sub)PS. DORV, double outlet right ventricle; PS, pulmonary stenosis; TGA, transposition of the great arteries; VSD, ventricular septal defect.
Clinical data collected
Recorded variables included anatomy, surgical history, baseline rhythm, QRS duration on the first 12-lead ECG during the study period and supraventricular or ventricular arrhythmias. QRS duration was measured manually. Supraventricular tachycardia (SVT) included clinically documented atrial tachycardia, atrial flutter (AFl), atrial fibrillation (AF), atrioventricular nodal re-entrant tachycardia (AVNRT) and SVT of unspecified type; isolated short atrial runs on ambulatory monitoring were not included. Sustained ventricular tachycardia (VT) was defined as lasting at least 30 s or requiring earlier termination because of haemodynamic compromise. Pulmonary hypertension was defined by the contemporaneous diagnosis of the specialist ACHD or pulmonary hypertension team, supported by clinical, imaging and, where available, invasive haemodynamic findings; a single current threshold was not applied retrospectively. Operations were classified as palliative or reparative (biventricular repair or Fontan-type surgery); operative categories and detailed operative classifications are detailed in online supplemental figure 1 and online supplemental methods, respectively. Patients who underwent initial palliation followed by definitive repair were classified according to their definitive repair and circulation at study entry.
Statistical analysis
Analyses were performed using R V.4.5.1. Continuous variables are presented as median (IQR) and categorical variables as n (%); groups were compared using Wilcoxon rank-sum and χ² tests, respectively.
Follow-up began at the first ACHD assessment. Both composite endpoints were analysed as time to first component event, with event-free patients censored at their last clinical contact. The primary composite endpoint was all-cause death, heart or heart–lung transplantation, aborted SCD or appropriate implantable cardioverter-defibrillator (ICD) shock. The secondary composite endpoint was SCD, heart or heart–lung transplantation, aborted SCD or appropriate ICD shock. SCD was defined as death within 1 hour of symptom onset, sudden unexplained witnessed death or SCD recorded on the death certificate.5 9 Cause of death, including classification as SCD, was assigned following review of contemporaneous clinical records and linked Office for National Statistics mortality data. Antitachycardia pacing without a shock was not included in either endpoint. Associations with outcomes were assessed using univariable and multivariable Cox proportional hazards regression. Modelling was restricted to patients with biventricular repair to provide a clinically homogeneous subgroup relevant to routine assessment of repaired DORV.6 The primary composite describes overall adverse prognosis and was not intended to distinguish arrhythmic from heart failure risk or to guide a specific intervention. Individual components are reported separately.
For the primary endpoint, covariates for the multivariable model were selected using forward and backward stepwise procedures. The model was limited to three variables because only 27 primary endpoint events occurred; these analyses were exploratory. Missing values were not imputed; each model used complete observations for the variables included. Tests were two-sided and a p value of <0.05 was considered statistically significant. Primary and secondary endpoint curves were estimated using the Kaplan-Meier method. The proportional hazards assumption was assessed using scaled Schoenfeld residuals for each covariate and globally.
Results
Patient characteristics
Demographics and cardiac anatomy
In total, 254 patients (median age 20 (IQR 17.6 to 29.2) years, 47.2% female) were identified and included in this study. According to the anatomical classification, 34 (13.4%) patients had VSD-type DORV, 79 (31.1%) patients ToF-type, 22 (8.7%) TGA-type without pulmonary stenosis and 29 (11.4%) TGA-type DORV with pulmonary stenosis. Patients with complex anatomies not amenable to biventricular repair included 85 (33.5%) patients with highly complex anatomy and 5 (2.0%) patients with a remote or non-committed VSD (table 1 for baseline characteristics; online supplemental table 1 for characteristics for all anatomical subgroups).
Table 1. Baseline characteristics of the study cohort by anatomical group.
| Variable | All (n=254) |
Groups 1–2 (VSD-type and ToF-type) (n=113) |
Groups 3–4 (TGA-type±PS) (n=51) |
Group 5 (Complex and remote VSD) (n=90) |
P value* |
|---|---|---|---|---|---|
| Age, years | 20 (17.6–29.2) | 19.5 (17.5–27.7) | 22 (18.1–31.2) | 20.2 (17.6–30.1) | 0.94 |
| Female | 120 (47.2) | 49 (43.4) | 20 (39.2) | 51 (56.7) | 0.03 |
| Associated anatomical features/complications | |||||
| Dextrocardia | 21 (8.3) | 7 (6.2) | 6 (11.8) | 8 (8.9) | 0.79 |
| Isomerism | 22 (8.7) | 6 (5.3) | 1 (2) | 15 (16.7) | 0.0005 |
| Aortic stenosis | 14 (5.5) | 8 (7.1) | 2 (3.9) | 4 (4.4) | 0.59 |
| Coarctation of aorta | 27 (10.6) | 10 (8.8) | 9 (17.6) | 8 (8.9) | 0.50 |
| Aortic arch hypoplasia | 17 (6.7) | 5 (4.4) | 3 (5.9) | 9 (10) | 0.12 |
| Azygos continuation | 19 (7.5) | 3 (2.7) | 2 (3.9) | 14 (15.6) | 0.0003 |
| Atrial septal defect | 30 (11.8) | 10 (8.8) | 7 (13.7) | 13 (14.4) | 0.0005 |
| Mitral/tricuspid atresia | 19 (7.5) | 0 (0.0) | 0 (0.0) | 19 (21.1) | – |
| Pulmonary hypertension | 27 (10.6) | 5 (4.4) | 9 (17.6) | 13 (14.4) | 0.14 |
| Surgical strategy | |||||
| Type of repair | 0.0005 | ||||
| ToF-type | 75 (29.5) | 75 (66.4) | 0 (0.0) | 0 (0.0) | |
| Fontan | 58 (22.8) | 0 (0.0) | 0 (0.0) | 58 (64.4) | |
| Tunnel-type | 43 (16.9) | 35 (31) | 6 (11.8) | 2 (2.2) | |
| LV–PA conduit | 2 (0.8) | 0 (0.0) | 2 (3.9) | 0 (0.0) | |
| Arterial switch | 18 (7.1) | 0 (0.0) | 18 (35.3) | 0 (0.0) | |
| Rastelli | 15 (5.9) | 0 (0.0) | 15 (29.4) | 0 (0.0) | |
| Mustard | 3 (1.2) | 0 (0.0) | 3 (5.9) | 0 (0.0) | |
| Palliative | 33 (13) | 3 (2.7) | 6 (11.8) | 24 (26.7) | |
| None | 7 (2.8) | 0 (0.0) | 1 (2) | 6 (6.7) | |
| Age at first operation, years | 5.3 (2.1–14.9) | 4.2 (1.4–9.5) | 6 (2–14.7) | 12.7 (5.2–22.4) | 0.0008 |
| Number of repair operations | 2 (2–3) | 3 (2–3) | 2 (2–3) | 2 (1–3) | 0.0001 |
| Electrophysiology | |||||
| Baseline rhythm | 0.1 | ||||
| Sinus | 167 (65.7) | 83 (73.5) | 32 (62.7) | 52 (57.7) | |
| Paced | 22 (8.7) | 8 (7.1) | 3 (5.9) | 11 (12.2) | |
| Atrial fibrillation | 1 (0.4) | 1 (0.9) | 0 (0.0) | 0 (0) | |
| Atrial flutter | 2 (0.8) | 0 (0) | 0 (0.0) | 2 (2.2) | |
| Atrial tachycardia | 0 (0) | 0 (0.0) | 0 (0) | 0 (0.0) | |
| Other | 2 (0.8) | 0 (0) | 0 (0) | 2 (2.2) | |
| Unknown | 60 (23.6) | 21 (18.6) | 16 (31.4) | 23 (25.6) | |
| SVT at baseline | 16 (6.3) | 8 (7.1) | 0 (0) | 8 (8.9) | 0.21 |
| VT at baseline | 12 (4.7) | 6 (5.3) | 2 (3.9) | 4 (4.4) | 0.99 |
| Baseline QRS | 139 (111–160) | 150 (134.3–166.8) | 154 (126–163) | 111 (98–127.5) | 0.0001 |
Categorical variables displayed as n (%). Numerical variables shown as median (IQR).
Comparison of groups 1–4 versus 5. A p value <0.05 was indicative of statistical significance (shown in bold font).
LV, left ventricle; PA, pulmonary artery; PS, pulmonary stenosis; SVT, supraventricular tachycardia; TGA, transposition of the great arteries; ToF, tetralogy of Fallot; VSD, ventricular septal defect; VT, ventricular tachycardia.
Surgical history
Overall, 247 (97.2%) patients had undergone at least one palliative or reparative operation (median 2 (range 0 to 7)). 33 (13%) underwent palliative procedures only, while 214 (84.3%) had at least one definitive operation (72.9% biventricular repair; 27.1% Fontan-type surgery). The median age at definitive surgery was 1.9 (0.4 to 8.6) years: 1.8 (0.4 to 7.3) years for biventricular repair and 6.6 (4.3 to 12.1) years for Fontan-type surgery; 41 (35%) underwent surgery aged >10 years. Biventricular strategies comprised ToF-type repair in 75 (48.1%), tunnel-type repair in 43 (27.6%), arterial switch or equivalent in 18 (11.5%), Rastelli repair in 15 (9.6%), atrial switch in 3 (1.9%) and left ventricle-to-pulmonary artery conduit in 2 (1.3%).
Electrophysiology
The underlying cardiac rhythm was sinus in most patients (167, 65.7%), whereas 22 (8.7%) were paced, 3 (1.2%) patients were in AF or AFl and 2 (0.8%) had a junctional rhythm (classified as ‘other’) at baseline. 60 patients (23.6%) could not be classified because no baseline ECG was available within 3 months of ACHD follow-up. QRS duration at baseline was >180 ms in 7 (2.8%) cases and >170 ms in 27 (10.6%) cases. Implantable devices were present in 71 (28%) patients: 52.1% pacemakers, 33.8% ICDs and 14.1% cardiac resynchronisation therapy-ICDs (CRT-Ds). The majority of patients with a device (n=41, 57.7%) had this implanted after their transition to ACHD services. The main reason for pacemaker implantation was postoperative high-degree atrioventricular block. Of 34 (13.4%) patients who received an ICD or CRT-D, 14 (41.2%) were implanted as primary prevention. Of the seven patients with baseline QRS duration >180 ms, six (85.7%) had undergone biventricular repair, of whom four (66.7%) experienced the primary endpoint.
Arrhythmias during follow-up
Different types of SVT were recorded during the follow-up period, with 80 (31.5%) patients experiencing at least one episode of SVT. Atrial tachycardia was the most frequently recorded SVT in our study population, observed in 44 (17.3%) patients. Patients who had undergone a Fontan-type or Rastelli-type operation were at increased risk of atrial tachycardia compared with other patients (p=0.003, p=0.048, respectively). Other arrhythmias documented during follow-up included AF (21, 8.3%), AFl (23, 9.1%) and AVNRT (4, 1.6%). 21 (8.3%) patients developed more than one type of SVT.
The QRS duration increased from baseline assessment to follow-up by 6 (−1 to 14.5) ms, with an average increase of 0.4 (−0.1 to 1.1) ms per year. There was no significant difference in the change in QRS duration between patients with complex anatomy versus the remainder (p=0.91, figure 2), or between ToF-type DORV and TGA-type DORV (p=0.81).
Figure 2. QRS duration (ms) of the overall study population, separated into anatomical groups A1, A2 and B at baseline and follow-up (Wilcoxon signed-rank test, p<0.0001). Each panel displays a histogram with the median QRS duration indicated by a dashed line. In the follow-up histogram, the baseline median is also superimposed in red to allow for comparison.
A total of 33 (13.0%) patients developed ventricular arrhythmias during follow-up, with an incidence of 1.03%/person-year. 12 (4.7%) patients had a history of VT prior to baseline assessment. There was no statistically significant difference in the incidence of VT between anatomical groups (p=0.42). 28 (11%) patients had a defibrillator implanted during follow-up (35.7% primary prevention, 64.3% secondary prevention). An appropriate ICD shock was delivered in 10 (4.0%) patients (incidence 0.3%/person-year), of whom 3 (30.0%) were ToF-type patients and 3 (30.0%) were in the TGA with pulmonary stenosis group.
Catheter ablation was performed in 43 (17.0%) patients during follow-up (1.35%/person-year), mainly for atrial tachycardia (27, 10.6%), AF (6, 2.4%) or AVNRT (3, 1.2%); three patients underwent VT ablation. Only two patients required repeat ablation. Among patients with SVT, sustained VT or arrhythmia ablation during follow-up, 30/80 (37.5%), 22/33 (66.7%) and 17/43 (39.5%), respectively, also experienced the primary endpoint; these groups overlap.
Long-term outcomes
A total of 60 (23.6%) patients experienced the primary composite outcome of all-cause mortality, heart or heart–lung transplantation, aborted SCD or appropriate ICD shock (incidence 1.9%/person-year; figure 3A). Over 3195 patient-years (median follow-up 12.4 (7.4 to 17.3) years), 47 (18.5%) patients died, with a mortality of 1.5%/person-year. Heart failure was the leading cause of death (n=19, 40.4%); pulmonary hypertension was the cause of heart failure in 3 (15.8%) patients. One (2.1%) patient died from Fontan failure (table 2; online supplemental table 2). Four patients (1.6%) underwent heart transplantation, half with complex DORV. A minority died from non-cardiac causes, including haemorrhage (n=4, 8.5% of total, of which 75% cerebral and 25% pulmonary), infection (n=6, 12.8%), liver/renal failure and emphysema (n=1, 2.1% each). One patient died following non-cardiac surgery.
Figure 3. Survival free from the primary (a) and secondary (b) endpoints. Cumulative incidence of the primary (c) and secondary (d) endpoint according to the presence of pulmonary hypertension, age >29.5 years or QRS duration >180 ms at baseline. ICD, implantable cardioverter-defibrillator; SCD, sudden cardiac death; Tx, treatment.
Table 2. DORV outcomes by anatomical group.
| Variable | All (n=254) |
Groups 1–2 (VSD-type and ToF-type) (n=113) |
Groups 3–4 (TGA-type±PS) (n=51) |
Group 5 (Complex and remote VSD) (n=90) |
P value* |
|---|---|---|---|---|---|
| Follow-up period, years | 12.4 (7.4–17.3) | 12.3 (7.2–17.1) | 12.0 (8.2–16.7) | 12.7 (7.1–19.2) | 0.67 |
| Electrophysiology | |||||
| SVT during follow-up | 80 (31.5) | 24 (21.2) | 17 (33.3) | 39 (43.3) | 0.009 |
| VT during follow-up | 33 (13) | 17 (15) | 8 (15.7) | 8 (8.9) | 0.15 |
| SVT type | 0.78 | ||||
| Atrial fibrillation | 21 (21.2) | 7 (25.9) | 6 (24.0) | 8 (17.0) | |
| Atrial flutter | 23 (23.2) | 6 (22.2) | 5 (20.0) | 12 (25.5) | |
| Atrial tachycardia | 44 (44.4) | 10 (37.0) | 13 (52.0) | 21 (44.7) | |
| AVNRT | 4 (4) | 0 (0) | 0 (0) | 4 (8.5) | |
| SVT (unspecified) | 7 (7.1) | 4 (14.8) | 1 (4.0) | 2 (4.3) | |
| Pacemaker during follow-up | 13 (5.1) | 2 (1.8) | 3 (5.9) | 8 (8.9) | 0.07 |
| ICD during follow-up | 28 (11) | 14 (12.4) | 10 (19.6) | 4 (4.4) | 0.02 |
| Ablation during follow-up | 43 (17) | 12 (10.6) | 11 (21.6) | 20 (22.2) | 0.09 |
| Appropriate shock delivered | 10 (4) | 4 (3.5) | 4 (7.8) | 2 (2.2) | 0.58 |
| Mortality | |||||
| Death | 47 (18.5) | 12 (10.6) | 13 (25.5) | 22 (24.4) | 0.07 |
| Cause of mortality | 0.65 | ||||
| SCD | 12 (25.5) | 2 (16.7) | 3 (23.1) | 7 (31.8) | |
| Heart failure | 19 (40.4) | 6 (50) | 4 (30.8) | 9 (40.9) | |
| Infection | 6 (12.8) | 0 (0) | 4 (30.8) | 2 (9.1) | |
| Bleeding | 4 (8.5) | 1 (8.3) | 2 (15.4) | 1 (4.5) | |
| Other | 6 (12.8) | 3 (25) | 0 (0) | 3 (13.6) | |
Categorical variables displayed as n (%). Numerical variables shown as median (IQR).
Comparison of groups 1–4 versus 5. A p value <0.05 was indicative of statistical significance (shown in bold font).
AVNRT, atrioventricular nodal re-entrant tachycardia; DORV, double outlet right ventricle; ICD, implantable cardioverter-defibrillator; PS, pulmonary stenosis; SCD, sudden cardiac death; SVT, supraventricular tachycardia; TGA, transposition of the great arteries; ToF, tetralogy of Fallot; VSD, ventricular septal defect; VT, ventricular tachycardia.
SCD was a significant cause of mortality, occurring in 12 (4.7%) patients (incidence 0.38%/person-year). SCD occurred more frequently in those with complex anatomy compared with all other groups combined (0.6%/person-year, p=0.03). There were no instances of SCD in patients within the TGA without pulmonary stenosis group or the remote VSD group. SCD patients were generally younger than those who died from other causes (29 (24 to 37) vs 42 (34 to 51) years, p=0.04). Three of the patients who suffered SCD had experienced an episode of VT during the follow-up period of the study. Two (0.8%) patients had undergone ICD implantation prior to the non-aborted SCD event. There were four (1.6%) instances of an aborted SCD (incidence 0.1%/person-year), with three (1.2%) patients having a defibrillator implanted as secondary prevention (one patient turned down ICD implantation).
Outcome predictors in DORV
Unoperated or palliated DORV (eg, Blalock-Taussig shunt alone) was a strong predictor of the primary composite endpoint, associated with an over three-fold risk (HR 3.59, 95% CI 2.12 to 6.09, p<0.0001; online supplemental figure 2). Among the 156 patients who had undergone a biventricular repair, 27 (17.3%) experienced the primary composite endpoint. On univariate Cox proportional hazards regression analysis, the following variables were identified as significant in this subgroup: older age (HR 1.09 per year, 95% CI 1.05 to 1.14, p=0.0002), the presence of pulmonary hypertension (HR 5.84, 95% CI 2.06 to 16.56, p=0.0004), baseline QRS duration >180 ms (HR 6.78, 95% CI 2.2 to 20.7, p=0.003), history of SVT (HR 7.05, 95% CI 2.35 to 21.2, p=0.003), Rastelli-type repair (HR 2.66, 95% CI 1.14 to 6.21, p=0.03), age at first reparative surgery (HR 1.06, 95% CI 1.02 to 1.09, p=0.001) and number of reparative surgeries (HR 1.35, 95% CI 1.01 to 1.81, p=0.001). In exploratory multivariable Cox regression analysis restricted to this subgroup, older age, pulmonary hypertension and baseline QRS >180 ms remained associated with the primary endpoint (table 3, figure 3C). The global test of the proportional hazards assumption yielded p=0.78; covariate-specific results are reported in table 3.
Table 3. Exploratory univariable and multivariable Cox proportional hazards analysis for the composite outcome of all-cause mortality, heart or heart–lung transplantation, aborted SCD or appropriate ICD shock in adults with DORV after biventricular repair.
| Univariate HR (95% CIs) |
Multivariate HR (95% CIs) | P value | |
|---|---|---|---|
| Age (year) | 1.09 (1.05 to 1.14) | 1.09 (1.05 to 1.14) | 0.0001 |
| Pulmonary hypertension | 5.84 (2.06 to 16.56) | 5.7 (2.03 to 16) | 0.0009 |
| Baseline QRS >170 ms | 2.74 (1.19 to 6.34) | ||
| Baseline QRS >180 ms | 6.78 (2.2 to 20.7) | 6.41 (2.12 to 19.37) | 0.008 |
| Prior SVT history | 7.05 (2.35 to 21.2) | ||
| Rastelli operation | 2.66 (1.14 to 6.21) | ||
| No. reparative operations | 1.35 (1.01 to 1.81) | ||
| Age at first reparative operation | 1.06 (1.02 to 1.09) |
Complete observations in univariable models: age, n=156; pulmonary hypertension, n=156; QRS >170 ms, n=156; QRS >180 ms, n=156; prior SVT, n=156; Rastelli operation, n=156; number of reparative operations, n=156; age at first reparative operation, n=156. Final multivariable model: n=156, primary events=27. Scaled Schoenfeld-residual tests: age p=0.58; pulmonary hypertension p=0.39; QRS >180 ms p=0.90; global p=0.78.
DORV, double outlet right ventricle; ICD, implantable cardioverter-defibrillator; SCD, sudden cardiac death; SVT, supraventricular tachycardia.
Discussion
This study reports on a large, contemporary multicentre cohort of adults with DORV. Despite excellent long-term survival in many patients, late adverse events, including death, transplantation, aborted SCD and appropriate ICD shocks, remained common, affecting nearly one-quarter of the cohort over long-term follow-up. Definitive surgical repair or Fontan-type surgery were strongly associated with better outcomes compared with unrepaired or palliated patients. In exploratory analysis of patients with biventricular repair, older age, a prolonged QRS duration (>180 ms) and pulmonary hypertension were associated with the primary composite outcome. While advances in surgical repair have transformed the natural history of DORV, a substantial burden of late complications persists, necessitating lifelong ACHD follow-up.
DORV refers to a ventriculo-arterial connection in which both great vessels arise predominantly or entirely from the right ventricle.10 Hearts with DORV display a broad spectrum of anatomical variants, ranging from a subaortic VSD to functionally univentricular hearts.1 11 Accurate classification of the type of DORV is essential, both in early life when considering the type of repair and during adulthood when addressing long-term sequelae and residual lesions. The classification used in this study reflects both the anatomical characteristics and the type of operative strategy employed, both of which dictate long-term outcomes.3 A third of our population consisted of patients not amenable to biventricular repair, the majority of whom had highly complex anatomy rather than just a remote VSD. While many experts feel that biventricular repair should be pursued in most patients, we found no difference in terms of the morbidity–mortality endpoints in adult survivors with biventricular repair versus a Fontan-type operation, at least at mid-term follow-up. Inevitably, the types of complication do differ between these groups, yet the overall burden remains high even in those with biventricular repair, who still require close long-term follow-up.12
In our population, one in five patients faced death, transplant or malignant arrhythmias over a 10-year follow-up. There was a threefold higher event rate in patients who were unoperated or received palliative shunts; these patients usually have chronic cyanosis with all the adverse sequelae that accompany this. Unoperated/palliated patients also typically present with adverse haemodynamics, with differing degrees of volume and/or pressure overload of the ventricles. In cases with an unprotected pulmonary circulation, pulmonary vascular disease develops early in life and significantly contributes to morbidity and mortality.
Pulmonary hypertension was also associated with adverse outcome after biventricular repair. Indeed, patients with pulmonary arterial hypertension following CHD repair are a growing population with a high morbidity and mortality, supporting timely initiation of pulmonary arterial hypertension therapies where indicated.13–15 Echocardiographic screening for evidence of pulmonary hypertension is a necessary component of lifelong specialised care, including in repaired DORV, though the criteria for suspecting pulmonary hypertension should be adapted to the underlying anatomy.16 In the presence of echocardiographic signs of pulmonary hypertension, further guideline-directed evaluation and management are applicable to this population.17 18
While most deaths were attributed to heart failure, roughly one quarter were sudden. The propensity for malignant arrhythmias is well documented in ToF,19–21 and historical DORV series also highlighted elevated SCD rates. Shen et al5 reported on a population with a median operative age of 10 years and a substantial late mortality at around 7 years, with SCD accounting for three-quarters of deaths. Later reports by Brown et al3 and Tateno et al4 5 described low SCD rates, though the former study assessed a purely paediatric cohort, while the latter only included patients with a specific type of DORV repair (ie, involving a right ventricle-to-pulmonary artery conduit). Our cohort was entirely composed of adult patients, many of whom were operated on in the pre-1980 surgical era and who are now manifesting heart failure, arrhythmias and other complications, as a result of the cumulative effects of previous surgeries (including atrial and ventricular scarring), residual haemodynamic lesions and pulmonary hypertension. Indeed, older age was associated with the composite endpoint after biventricular repair.
QRS duration >180 ms was associated with the composite endpoint after biventricular repair. QRS prolongation likely reflects a combination of surgical scar and adverse ventricular remodelling and increased significantly during follow-up in our cohort. Prolonged QRS is a recognised risk marker in ToF, particularly when ≥180 ms,20 22 23 and is associated with ventricular function and adverse events in systemic right ventricle physiology.21 Notably, QRS prolongation was observed across DORV subtypes, not only ToF-type. Recent lesion-specific risk models in repaired ToF emphasise that multimodal approaches integrating fibrosis assessment on cardiac magnetic resonance, biventricular function, exercise capacity and natriuretic peptides improve risk discrimination beyond single ECG metrics, reinforcing the need for comprehensive stratification.24
Arrhythmias were common in this cohort, as in other adult CHD populations.3 4 25 SVTs, often macro-re-entrant atrial tachycardia, typically reflect prior atriotomy/patch scars and persistent haemodynamic lesions and can precipitate decompensation, especially in the presence of ventricular dysfunction or pulmonary hypertension. Surveillance for the presence of both supraventricular and ventricular arrhythmia is important, with a proactive strategy combining medical therapy and catheter ablation being appropriate. In this cohort, ablation was frequently undertaken with a low need for repeat procedures, consistent with outcomes from other experienced CHD electrophysiology programmes and guideline recommendations.18 20 26 Device therapy was also common, with a roughly even split between ICDs (with or without CRT) for primary or secondary prevention, and pacemakers for bradycardia. Multidisciplinary care, involving close collaboration between adult CHD cardiologists and electrophysiologists/device specialists, with meticulous preprocedural planning (vascular access, baffles/conduits, intracardiac anatomy) is essential to preserve safety and efficacy. Further large studies are needed to identify ICD-specific predictors of outcome in DORV, that can guide primary prevention ICD implantation, the benefits of which should be weighed against the long-term complications in terms of inappropriate shocks, device-related complications and the psychological impact on young adults living with a device.27 28
Limitations
The principal limitation is the small number of events: 27 among 156 patients with biventricular repair. Stepwise selection and the small number with QRS duration >180 ms may produce unstable estimates and overstate associations. The multivariable findings are therefore exploratory, apply only to this subgroup and require validation. The retrospective design and selection by entry to ACHD follow-up may also have introduced survivorship bias. It is notable that the first surgical intervention and definitive repair occurred relatively late in the study cohort compared with modern practices, which may potentially influence late outcomes. We chose to perform multivariable Cox regression analysis only on patients who had undergone biventricular repair, that is, excluding patients with DORV who were unrepaired or palliated, as well as those who underwent Fontan-type surgery. Indeed, it is expected that unrepaired patients and those with a Fontan-type physiology follow a clinical trajectory that differs significantly from that of patients who have undergone biventricular repair and should be assessed separately. Our study was not sufficiently powered for formal subgroup survival analysis by anatomy. Moreover, the small number of events precluded multivariable analyses for the secondary endpoint. Appropriate ICD shocks can be observed only in patients with a defibrillator. Quantitative ventricular and valvular function, natriuretic peptides, invasive haemodynamics and exercise capacity were not included in the analysis of this highly heterogenous population spanning almost three decades. Future studies should consider including such information, especially if analysis of the different subgroups of DORV is contemplated. This was the first large, adult-only, multicentre DORV outcome study, describing the long-term effects of this rare group of conditions. Larger international cohorts are required to validate our findings and assist in the clinical care of this expanding population.
Conclusion
Despite major advances in the care of patients with DORV, late morbidity and mortality remain substantial. Heart failure, arrhythmia and pulmonary hypertension are the main drivers of morbidity and mortality. SCD appears prevalent in this population and requires further investigation to identify high-risk patients who may benefit from primary prevention with ICD implantation. ACHD services have an integral role to play in preventing the development of life-threatening sequelae in these patients through close monitoring and accurate risk stratification.
Supplementary material
Footnotes
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Data availability free text: Patient data were kept strictly confidential, and the dataset is not publicly available to protect patient privacy.
Ethics approval: The study was approved by the UK Health Research Authority (IRAS ID: 275809), with consent waived for anonymised routinely collected data.
Data availability statement
Data may be obtained from a third party and are not publicly available.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data may be obtained from a third party and are not publicly available.