Diana Zannino

Three decades later: the fate of the population of patients who underwent the Atriopulmonary Fontan procedure

OBJECTIVE To review our experience of patients with an atrio-pulmonary Fontan circulation to determine their long-term outcomes. METHODS AND RESULTS A retrospective analysis of long-term follow-up data using the Australia and New Zealand Fontan Registry was performed. There were 215 patients surviving hospital discharge after an atrio-pulmonary Fontan completion. A total of 163 patients were alive at latest follow-up, with 52 deaths. Twelve patients had required heart transplantation and 95 had Fontan failure (death, transplantation, Fontan takedown, Fontan conversion, severe systemic ventricular dysfunction or NYHA≥3). Twenty-eight year freedom from death, death and transplantation and Fontan failure were 69% (95% CI 61-78%), 64% (95% CI 56-74%) and 45% (95% CI 36-55%) respectively. One hundred and thirty patients developed atrial arrhythmias. Freedom from arrhythmia at 28years post Fontan was 22.9% (95% CI: 15.1-30.8). Development of arrhythmia increased the likelihood of death (HR:2.97, 95%CI 1.50-5.81; p=0.002), death and heart transplantation (HR:3.11, 95%CI 1.64-5.87; p<0.001) and Fontan failure (HR:4.78 95%CI 2.95-7.74; p<0.001). There were 42 patients who had thromboembolic events, of which only 12 were therapeutically anti-coagulated. Two-thirds of the surviving patients (86/126) with an intact atrio-pulmonary Fontan were regularly reviewed. Patients receiving follow-up care with general cardiologists without specialised training were more likely to face Fontan failure than those managed by cardiologists with specialist training in congenital heart disease (HR: 1.94, 95% CI 1.16-3.24; p=0.02). The majority of the surviving patients (81/86) remained physically active and almost two-thirds (54/86) were currently employed. CONCLUSION Two-thirds of the patients who underwent a classical atrio-pulmonary Fontan are still alive 3 decades later. The majority are affected by the burden of arrhythmias but remain functionally active today. These challenging patients should only receive follow-up care from cardiologists with specialised training.

Long-term results of anatomic correction for congenitally corrected transposition of the great arteries: A 19-year experience

Objective: The surgical indication, timing, strategy, and surgical technique for anatomic correction of congenitally corrected transposition of the great arteries are challenging. We evaluated the long‐term results at The Royal Childrens Hospital Melbourne. Methods: Review of 32 successive anatomic corrections between 1996 and 2015. Results: Twenty‐one double‐switch (66%), 6 Senning/Bex‐Nikaidoh (19%), and 5 Senning/Rastelli (16%) procedures were performed (median age, 1.9 years). Median follow‐up was 5.4 years with 4 deaths and 1 heart transplant. Cumulative incidence of late reoperation was 8%, 29%, and 59% at 1, 5, and 10 years, respectively. Twenty‐six patients had full follow‐up with native hearts. Nineteen had normal left ventricle (LV) function. Late LV dysfunction, mostly mild, was not related to needing a pacemaker (P = .4) or a pulmonary artery band (PAB) (P = .08). Previous PAB was linked to the need for aortic valve surgery or neoaortic regurgitation moderate or greater (P = .03). Six required Senning revision. The introduction of the Shumacker modification of the Senning has generated stable pulmonary venous pathways. Six patients developed postoperative iatrogenic atrioventricular block dependent on a permanent pacemaker. Conclusions: Anatomic correction is a surgical challenge. It provides excellent functional outcomes in survivors with a significant need for reoperation and a definite risk of death or transplantation. Normal LV function should be expected in most patients. LV dysfunction was not linked to PAB or pacemaker requirement but surgery without LV training had better long‐term LV function. The Shumacker modification provided stable venous pathways. Iatrogenic atrioventricular block remains a challenge.

Ventricular assist device support in patients with single ventricles: the Melbourne experience

OBJECTIVES The capacity and limitations of ventricular assist device (VAD) support in single-ventricle physiology remains poorly understood. We aimed to review our experience in the use of VAD support in the single-ventricle circulation to determine its feasibility in this population. METHODS We reviewed our experience with VAD support in patients with single ventricles over the past 25 years. Fifty-seven patients received 64 runs of VAD support between 1990 and 2015 at a median age of 13 days [interquartile range (IQR) 4.1-99.4 days], of which 55 were supported for post-cardiotomy failure. The majority of patients received short-term VAD support, while 4 patients were either directly supported (1) or transitioned onto the Berlin Heart EXCOR (3). RESULTS The median duration of support was 3.5 days (IQR 2.8-5.2 days). Twelve patients suffered significant neurological complications, and thromboembolic events occurred in 8 patients. Twenty-nine of the 55 patients were successfully weaned off support (53%). There were 37 inpatient deaths, with a survival-to-hospital discharge rate of 33% (18 of 55). Of the 4 patients supported after early Fontan failure, 3 died. Having a higher mean arterial blood pressure on initiation of VAD support was the only significant predictor of death (hazards ratio 1.08; 95% confidence interval 1.03-1.14; P = 0.002). Patients who required a second run of support had higher hospital mortality (83% vs 63%; P = 0.84). Of the hospital survivors, 12 patients (63%) remain alive without heart transplantation at median 7.2 years (IQR 3.5-14.0) post VAD support. CONCLUSIONS VAD support in patients with a single ventricle has a high hospital mortality, with 1 of 3 patients surviving to discharge. Systemic VAD support is likely futile in the setting of early Fontan failure or when re-initiation of support is required.

Evidence of Microvascular Changes in the Retina following Kawasaki Disease.

It is unclear whether all children with Kawasaki disease (KD) have increased later cardiovascular risk. The retinal microvasculature reflects changes in the microcirculation and is associated with traditional cardiovascular risk factors and events. The aim of this study was to investigate retinal microvascular parameters in two populations of patients with previous KD and control participants. We performed case-control studies of 116 (57 patients and 59 control participants) Australian and 156 (78 patients and 78 control participants) Singaporean individuals, at least two years since their acute illness. Standardised retinal photographs were graded by trained technicians using a semi-automated software, which quantifies the retinal microvasculature (calibre, branching angle, fractal dimensions, and tortuosity). Retinal venules of Singaporean KD patients were 9.67 μm (95% CI 4.87 to 14.51, p < 0.001) larger than control participants following correction for traditional cardiovascular risk factors. An incremental increase in the size of retinal venules in those with coronary artery abnormalities was observed. There was limited evidence that retinal venules were larger in Australian KD patients with coronary artery abnormalities compared to control participants (7.34 μm, 95% CI 1.30 to 15.99, p = 0.10). Differences in retinal microvasculature were particularly evident in Singaporean KD patients. Larger retinal venules may reflect chronic inflammation and endothelial dysfunction, and are associated with coronary artery disease in adults.

Improved long-term outcomes in double-inlet left ventricle and tricuspid atresia with transposed great arteries: systemic outflow tract obstruction present at birth defines long-term outcome.

OBJECTIVES In 2 subtypes of functional single ventricle, double inlet left ventricle (DILV) and tricuspid atresia with transposed great arteries (TA-TGA), systemic output passes through an outflow chamber before entering the aorta. Intracardiac obstruction to this pathway causing systemic outflow tract obstruction (SOTO) may be present at birth or develop over time. Long-term survival after Fontan has not been defined. We defined outcomes utilizing records from 2 centres that were cross-checked with data from a bi-national Fontan Registry for completeness and accuracy. METHODS Two hundred and eleven patients were identified, 59 TA-TGA,152 DILV. Median follow-up was 17 years (range 4 days to 49.8 years). The Kaplan-Meier method was used for all of the time to event analyses and the log-rank test was used to compare the time-to-events. Cox proportional hazard models were used to test the association between potential predictors and time-to-event end-points. RESULTS TA-TGA had reduced survival compared to DILV (cumulative risk of death 28.8% vs 11%, hazard ratio (HR) 3.1 (95% confidence interval (CI) 1.6-6.1), P  = 0.001). In both groups, SOTO at birth carried a worse prognosis HR 3.54 (1.36-9.2, P  = 0.01). SOTO was not more common in either morphology at birth ( P  = 0.20). Periprocedural mortality accounted for 40% of deaths. Fontan was achieved in 82%, DILV were more likely to achieve Fontan than TA-TGA (91% vs 60%, P <0.001). After Fontan there were 9 deaths (4%) with no difference according to morphology. CONCLUSIONS Patients with TA-TGA have poorer outcomes than those with DILV, affecting survival and likelihood of achieving Fontan. SOTO at birth carries a high risk of mortality suggesting that, when present, initial surgical management should address this.

Predictors of outcomes in children awaiting heart transplantation: an experience from a National Paediatric Heart Transplantation Programme.

OBJECTIVES The risk of mortality while awaiting heart transplantation (HT) may be greater in the setting of a smaller population and lower donor organ rates. Optimizing allocation policy and identifying the most vulnerable patients will help reduce mortality. As such, we aimed to evaluate the predictors of outcomes in patients awaiting HT as part of a National Paediatric HT Programme. METHODS Between 1988 and 2015, 200 children were listed for HT as part of a National Paediatric HT Programme. We categorized patients as experiencing one of four competing events: (i) transplant, (ii) death, (iii) delisting for clinical deterioration and (iv) delisting for clinical improvement. Comparison was made across three study eras: Era 1: 1988-95; Era 2: 1996-2005; Era 3: 2006-15. A multivariable competing risk regression analysis was performed to determine the independent predictors of transplantation and the composite event of death or delisting for clinical deterioration. RESULTS Among the 200 patients listed, 60% (119/200) underwent transplantation, 22% (44/200) died on the waiting list, 7% (13/200) were delisted for clinical deterioration and 11% (21/200) were delisted due to clinical improvement, with 2% (3/200) being still active on the waiting list. The mortality-rate for patients who remained on the waiting list decreased from 27% in Era 1 to 18% in Era 3. The survival from wait-listing was 57, 47 and 39% at 5, 10 and 15 years, respectively. On multivariable competing risk regression, older age (HR 1.09, 95% CI 1.01-1.18, P = 0.029) and the absence of inotropic support (HR 2.22, 1.23-4.00, P = 0.0073) were predictors of reaching transplantation. Higher creatinine (per 20 µmol/l, HR 1.42, 1.03-1.95, P = 0.03) was a predictor of the composite endpoint of death or delisting for deterioration. CONCLUSIONS In this analysis of a National Paediatric HT Programme, waiting-list mortality has decreased over time though it remains higher than countries with higher donor rates. The requirement for inotropic support and worsening renal function were predictors of failure to reach transplantation. These patients are likely to benefit the most from ventricular-assist device therapy and higher priority listing.

Forward Flow Through the Pulmonary Valve After Bidirectional Cavopulmonary Shunt Benefits Patients at Fontan Operation

BACKGROUND The impact of additional pulmonary forward flow (APF) through the pulmonary valve at the time of bidirectional cavopulmonary shunt (BCPS) is unknown. METHODS Between 2000 and 2010, 276 patients had BCPS and 126 of them were selected, including 60 patients with APF via pulmonary valve and 66 patients, in whom the pulmonary valve was closed. We compared the length of hospital stay and duration of pleural drainage at BCPS and Fontan operations. We also compared the number of surgical interventions before BCPS, the number of operations between BCPS and Fontan operation, Nakata index prior to Fontan operation, grade of atrioventricular valve regurgitation (AVVR), and oxygen saturations prior to Fontan operation. RESULTS Prior to BCPS, 20% (12 of 60) of patients with APF and none without APF had pulmonary artery (PA) banding. More patients without APF had systemic-to-PA shunts (p < 0.01). Fontan operation was completed in 58% (35 of 60) of patients with APF and in 68% (45 of 66) of patients without APF (p = 0.34). There was no difference in the length of hospital stay or duration of pleural drainage at BCPS. No significant difference was observed in the number of surgical procedures between BCPS and Fontan operation, grade of AVVR or oxygen saturations before Fontan operation. Children with APF had a higher Nakata index (p = 0.02) prior to Fontan operation, shorter duration of pleural drainage (p = 0.009) and shorter hospital stay (p = 0.009) after Fontan operation. CONCLUSIONS Children with APF at BCPS had better developed PAs, shorter duration of pleural drainage, and shorter hospital stay after Fontan operation.

Laryngeal ultrasound detects a high incidence of vocal cord paresis after aortic arch repair in neonates and young children

Objectives: To determine the incidence of vocal cord paresis (VCP) after neonatal aortic arch repair/Norwood‐type procedure, and the effectiveness of noninvasive laryngeal ultrasound in detecting VCP compared with gold standard invasive nasoendoscopy. Methods: Fifty‐two patients who underwent an arch repair (39 of 52; 75%) or Norwood‐type procedure (13 of 52; 25%) via sternotomy between April 1, 2015, and April 30, 2017 underwent laryngeal ultrasound (50 of 52; 96%) and/or flexible fiber optic nasoendoscopy (39 of 52; 75%) at 48 to 72 hours after endotracheal extubation. Primary arch diagnoses were coarctation in 56% (29 of 52), hypoplastic left heart syndrome in 17% (9 of 52), isolated hypoplastic arch in 17% (9 of 52), and interrupted aortic arch in 10% (5 of 52). The median patient age at surgery was 5.5 days (interquartile range, 4.0–12.5 days). Fifteen patients (15 of 52; 29%) required preoperative intubation. Results: Left VCP was present in 59% (23 of 39) of patients on nasoendoscopy and in 59% (27 of 46) of patients on laryngeal ultrasound, and 4 additional patients had inconclusive ultrasound results. There was agreement between the results of nasoendoscopy and conclusive ultrasound in all cases. The overall sensitivity, specificity, positive and negative predictive values, and Cohens kappa coefficient of laryngeal ultrasound compared with nasoendoscopy for the detection of left VCP were 95%, 88%, 91%, 93%, and 0.83, respectively. On multivariable analysis, preoperative intubation and arch repair techniques other than the Norwood procedure were associated with left VCP (odds ratio, 12.7; P = .03; and 14.1; P = .03, respectively). Conclusions: There is a high incidence of VCP after arch repair via sternotomy. Laryngeal ultrasound seems to be an effective and noninvasive method for detecting VCP in neonates and young children.

Changes in carotid artery intima-media thickness during the cardiac cycle – a comparative study in early childhood, mid-childhood, and adulthood

BACKGROUND Carotid intima-media thickness (CIMT), an ultrasonographic marker of cardiovascular risk, is increasingly used in adults and children. The choice of specific images used to quantify CIMT from a cine sequence is often based on image quality rather than on a consistent point in the cardiac cycle. This methodological study quantified the imprecision that may be introduced by variation of CIMT during the cardiac cycle. PROBANDS AND METHODS Data from four-year-olds, 11 to 12-year-olds, and adults (n=30 each age group) were selected retrospectively from two population-derived studies. Far wall CIMT of the right common carotid artery was measured at end-diastole and peak systole using standardized protocols. All images were analysed using semi-automated edge-detection software. RESULTS In all age groups CIMT varied significantly during the cardiac cycle and was largest at end-diastole. The mean difference in CIMT between end-diastole and peak systole was greater in four-year-olds (38 μm; 95 % confidence interval (CI) 33 to 43 μm) and 11 to 12-year-olds (31 μm; CI 26 to 36 μm) than in adults (18 μm; CI 16 to 22 μm). Carotid IMT increased by 8.8 % (CI 7.7 to 9.8 %), 6.9 % (CI 5.8 to 8.1 %), and 3.8 % (CI 3.1 to 4.5 %) between minimum and maximum arterial diameter in four-year-olds, 11 to 12-year-olds, and adults, respectively. The greatest variation in CIMT during the cardiac cycle was observed in children (up to 14 %). CONCLUSIONS Inconsistent timing of CIMT measurement during the cardiac cycle is an avoidable source of imprecision, especially in children, in whom inter-individual differences are smallest. As CIMT is largest at end-diastole, this is the most appropriate time point for consistent and comparable measurements to be made.

Mid-term outcomes of congenital mitral valve surgery: Shone’s syndrome is a risk factor for death and reintervention†

OBJECTIVES To study the recent trends and outcomes of congenital mitral valve surgery in children. METHODS From 2008 to 2014, 84 procedures in 66 consecutive patients (41 procedures in 31 patients with mitral stenosis and 43 procedures in 35 patients with mitral regurgitation) were retrospectively evaluated. The mean age at surgery was 4.3 ± 5.4 years, and 27 patients (41%) were neonates or infants. RESULTS Seven (11%) patients died during the follow-up period of 3.2 ± 2.3 years and 5 (71%) were <1 year. Ten mitral valve replacements were performed in 8 patients, including 1 pulmonary valve homograft, 3 Contegra conduits of 12 mm thickness in the intra-annular position and 6 mechanical valves. Shones syndrome, dysplastic valve, a need for valve replacement and age <1 year were the risk factors for death or reoperation in a univariable analysis, while in a multivariable analysis of all patients, valve replacement and age <1 year remained as risk factors. In a multivariable analysis of 27 patients aged <1 year, mitral valve dysplasia was a significant risk factor for reoperation or death. The 5-year rate of freedom from death or reoperation in neonates or infants was 55% and that in patients aged >1 year was 88% (P = 0.003). CONCLUSIONS An age of <1 year, mitral valve dysplasia and a need for mitral valve replacement were associated with a higher incidence of death or reoperation. Primary mitral valve replacement or univentricular strategy may have to be considered for symptomatic neonates with Shones syndrome.