Jean-Benoit Thambo

Late Outcome of 132 Senning Procedures After 20 Years of Follow-Up

BACKGROUND Risk factors and rates of reoperation, arrhythmias, systemic right ventricular dysfunction (RVD), and late death after a Senning procedure were investigated. METHODS One-hundred thirty-two patients underwent a Senning operation between 1977 and 2004 (105 simple and 27 complex transpositions of the great arteries). Mean follow-up time was 19.5 ± 6.6 years. Surviving patients were evaluated by transthoracic echocardiography and electrocardiography. Right ventricular function was assessed in 70 patients by isotopic ventriculography or magnetic resonance imaging. RESULTS Operative and late mortality were 5.3% (7/132) and 9.6% (12/125), respectively. Nine patients were reoperated for left ventricular outflow tract obstruction or baffle stenosis. Survival rate was 91.5%, 91%, 89%, and 88% at 1, 5, 10, and 20 years, respectively. Probability of maintaining permanent sinus rhythm was 80%, 65%, 55%, and 44%. Twelve patients required pacemaker implantation. Probability of no supraventricular tachycardia, atrial flutter/fibrillation or ventricular tachycardia was 95.5%, 91.5%, 88%, and 75%, respectively. These parameters were similar for simple and complex transposition. Probability of right ventricular ejection fraction >40% was 100% at 5 and 10 years, and 98% at 20 years for simple transposition, and 100%, 92%, and 58% for complex transposition. This difference was statistically significant. Risk factors for RVD were complex transposition (p < 0.001), body weight (p = 0.008), no cardioplegia (p < 0.001), and tricuspid valve regurgitation (p = 0.004). CONCLUSIONS Senning procedure results in very good long-term survival out to 20 years. Both RVD and baffle stenosis were rare, but there was a concerning incidence of arrhythmia over time suggesting careful long-term surveillance.

2.3 Mb terminal deletion in 12p13.33 associated with oculoauriculovertebral spectrum and evaluation of WNT5B as a candidate gene

We describe a patient presenting with developmental delay, patent foramen ovale, moderate short QT interval, and facial dysmorphism including left microtia, preauricular tag and pit, wide left corner of the mouth, and left hemifacial microsomia, fitting with the oculoauriculovertebral spectrum. We identified a de novo 2.3 Mb deletion in the 12p13.33 region that contains eighteen genes. Amongst those, the WNT5B gene stands out as a possible candidate. However, we did not find any mutation of this gene neither in our patient nor in a series of 53 OAVS patients. The CACNA1C gene is interrupted by the centromeric breakpoint of the deletion and its inactivation probably accounts for the short QT interval of the patient. We speculate that the phenotype of our patient may be explained by the combined effect of the loss of several of the genes contained in the deleted chromosomal segment and of the inactivation of CACNA1C.

Subcutaneous implantable cardioverter defibrillators in children, young adults and patients with congenital heart disease

The demonstration of severe complications in patients implanted with a transvenous implantable cardioverter defibrillator (ICD) has led to the development of devices equipped with a subcutaneous lead. This new technique offers numerous advantages but also certain disadvantages. Various studies or anecdotal clinical cases have specifically been conducted with this subcutaneous defibrillation system in children and/or patients with congenital heart disease. Results of these studies suggest: 1) a high feasibility despite being limited by a selection process that excludes patients requiring permanent pacing and patients declared ineligible during pre-screening; 2) good efficacy of electrical shocks in reducing induced or spontaneous ventricular arrhythmias; 3) in this specific subset of patients, 2 types of complications have been particularly described: a risk of device exteriorization and infection, and a large number of inappropriate therapies primarily related to T-wave oversensing. The subcutaneous ICD could therefore constitute the gold standard for patients with complex congenital heart disease with no venous access to the heart or with a persistent shunt increasing the risk of systemic emboli as well as in young patients with channelopathy or hypertrophic cardiomyopathy not requiring long-term pacing. Technological change (reduction in device size, better differentiation between R- and T-waves, possibility of pacing if device coupled with a leadless pacemaker) could reduce the limitations and complications and thereby increase the indications in this sub-group of patients.

Liver stiffness measurements for evaluation of central venous pressure in congenital heart diseases

Objective Transient elastography (TE; Fibroscan, Echosens, France) is a non-invasive and reproducible approach to assess liver stiffness (LS). LS has been reported to be associated with fibrosis but central venous pressure (CVP) can also influence LS values. We sought to evaluate the correlation between LS and CVP in a large cohort of children and adults with congenital heart disease. Methods All patients referred in our institution between 2012 and 2013 for diagnostic or interventional right heart catheterisation (RHC) were prospectively enrolled excluding patients with acute heart failure, chronic alcohol abuse, chronic liver disease, severe obesity and ascites. Patients underwent LS measurement and CVP measurement by RHC under general anaesthesia within the same or subsequent day. Results Sixty children (7.4±5.5 years) and 36 adults (38±16 years) were included. Median CVP was 6 mm Hg (range 3–15), median LS was 5 kPa (range 2.8–47.2). LS significantly correlated with CVP (r=0.75, p<10−4). In the two subgroups (ie, children and adults), correlation was r=0.68 and r=0.84 (p<10−4), respectively. In the overall population, the area under the curve of LS for identification of CVP >10 mm Hg was 0.972 (95% CI 0.855 to 1; p<0.05). Optimal cut-off value of LS for detection of CVP >10 mm Hg was 8.8 kPa (sensitivity=91.67%, specificity=96.25%). Conclusions LS measurement using TE is a rapid and reliable method to evaluate CVP in patients with congenital heart disease.

New Family With Catecholaminergic Polymorphic Ventricular Tachycardia Linked to the Triadin Gene.

We describe a new family with cathecholaminergic polymorphic ventricular tachycardia (CPVT) linked to the Triadin gene. This is the second report of such a CPVT of autosomal recessive inheritance. Using an NGS panel including 42 genes involved in cardiac sudden death, 2 heterozygous pathogenic mutations (c.613C> T/p.Gln205* and c.22 + 29 A>G) were identified in the Triadin gene in 2 sibs who experienced early severe arrhythmias without evidence of CPVT diagnosis at first cardiac evaluation. However, significant arrhythmias occurred after catecholaminergic stimulation. Each of the TRDN mutations was inherited from a healthy parent. In this family, genetic studies permit confirmation of the CPVT diagnosis in the 2 affected sibs and permit the early diagnosis of the third asymptomatic child. It also helped guide the therapeutic strategy in this family.

Atypical male and female presentations of FLNA-related periventricular nodular heterotopia.

Periventricular nodular heterotopia, the most common form of cortical malformation in adulthood, is characterized by nodules of neurons ectopically placed along the lateral ventricles. Classically, ectopic nodules are bilateral and symmetric defining bilateral periventricular nodular heterotopia (BPNH). BPNH can lead to epilepsy and intellectual disability of variable severity. The X-linked dominant form of BPNH, related to mutations in FLNA encoding filamin A, is the major cause of BPNH, causing prenatal and neonatal lethality in males that explain the excess of affected women. However, few living males have been described with this condition. In addition, mutations in FLNA have been also exceptionally associated with unilateral nodular heterotopia. We describe here three new patients, all carrying a novel missense mutation in FLNA. Two of the patients were adult males with BPNH; both had normal cognitive development and one did not manifest any seizure until he died at age 57. The last patient was a female adult with epilepsy and focal nodules essentially located along the right ventricle. We compare the clinical and imaging data of our patients with those of previously described similar cases. The type and location of FLNA mutations leading to such atypical presentations are discussed.

Early to Midterm Results of Total Cavopulmonary Connection in Adult Patients

BACKGROUND Total cavopulmonary connection (TCPC) has not been studied in adults. We investigated early and midterm morbidity and mortality in adults undergoing TCPC and assessed risk factors for mortality. METHODS Between June 1994 and October 2010, 30 adults (21.3 ± 5.5 years) underwent TCPC (extracardiac conduit). Twenty-two patients who had palliated single ventricles underwent TCPC completions and 8 patients underwent TCPC conversions. Preoperative and perioperative data were reviewed retrospectively. RESULTS Six of 9 patients with preoperative atrial flutter or fibrillation or intraatrial reentry tachycardia were treated in the catheterization room. An aortic cross-clamp was necessary in 12 patients, and 16 TCPCs were fenestrated. Mean follow-up was 51 months (range, 4-198 months). Early mortality was 10%: 2 of 8 conversions and 1 of 22 completions. There was 1 late conversion death (at 56 months postoperatively). Postoperatively, 4 patients required pacemakers and 1 patient required long-term antiarrhythmic medication, but no heart transplantations were necessary. Risk factors for early mortality were arrhythmia (p = 0.02), aortic cross-clamp (p = 0.054), and extracorporeal circulation in hypothermia (p = 0.03). Risk factors for overall mortality were conversion (p = 0.047), absence of fenestration (p = 0.036), surgery before January 2006 (p = 0.036), aortic cross-clamp (p = 0.018), extracorporeal circulation in hypothermia (p = 0.008), and arrhythmia (p = 0.005). New York Heart Association functional class had improved at the last follow-up: preoperatively, 17 patients were in class II and 12 patients were in class III versus 18 patients in class I and 9 patients in class II postoperatively (p < 0.001). At the last clinical visit, systemic ventricular function was maintained, and no late supraventricular arrhythmia was found. CONCLUSIONS Early and midterm TCPC results for adults are encouraging for completion but are disappointing for conversion. Identified risk factors for mortality should improve patient selection for TCPC.

Left Atrial Appendage Closure in Patients with Atrial Fibrillation and Previous Intracerebral Hemorrhage

BACKGROUND Percutaneous left atrial appendage closure (LAAC) may be considered in patients with atrial fibrillation and contraindication for long-term anticoagulation. This study aimed to assess the safety and efficacy of LAAC followed by single antiplatelet therapy in patients with atrial fibrillation and previous spontaneous intracerebral hemorrhage (ICH). METHODS In this explorative, prospective, single-center study, consecutive patients who underwent LAAC because of previous spontaneous ICH over a period of 4 years were analyzed. Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2-VASc and HAS-BLED scores, respectively. Single antiplatelet therapy was given for at least 6 months post implantation. Clinical follow-up included cardiological evaluations at 1, 3, 6, and 12 months, and neurological evaluations at 3 and 12 months. RESULTS A total of 46 patients underwent LAAC with a mean follow-up of 12 ± 7 months. The observed annual rate of ischemic stroke was 4.35% compared with an expected rate of 7.23% according to the mean risk of the population based on CHA2DS2-VASc score, which translated into a 40% risk reduction. The observed annual rate of major bleeding was 4.35% compared with an expected rate of 8.05% according to the mean risk of the population based on HAS-BLED score, which translated into a 46% risk reduction. CONCLUSIONS LAAC followed by single antiplatelet therapy is feasible as an alternative to oral anticoagulation in high-risk patients with previous ICH, with an acceptable periprocedural risk. Longer follow-up in a larger number of patients will be needed to establish the effectiveness of LAAC relative to direct oral anticoagulants.

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Objective The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF). Methods and results Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV. Conclusion Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF.

Extending percutaneous left atrial appendage closure indications using the AMPLATZER™ Cardiac Plug device in patients with persistent left atrial appendage thrombus: The thrombus trapping technique

BACKGROUND Percutaneous left atrial appendage (LAA) closure has emerged as an alternative therapeutic option for the prevention of embolic stroke in high-risk patients with non-valvular atrial fibrillation. The presence of thrombus in the LAA is currently a contraindication to the procedure. AIM To describe a modified LAA closure technique that allows a safe procedure in patients with LAA thrombus. METHODS Between May 2013 and October 2014, LAA closure was performed in three patients with LAA thrombus (mean age 73.6±14 years; two men), using a modified technique that avoids manipulation of catheters or angiography in the LAA. RESULTS Two patients had persistent thrombus despite appropriate antithrombotic therapy, while the other patient had a contraindication to systemic anticoagulation. The procedure was successful using the modified implantation technique in all patients. The implanted device was the AMPLATZER™ Cardiac Plug (St. Jude Medical, Minneapolis, MN, USA) in one patient and the Amulet™ (St. Jude Medical, Minneapolis, MN, USA) in two patients. No periprocedural complications occurred. After a mean follow-up of 8±2 months, no deaths or late complications were observed. CONCLUSIONS Thrombus trapping is a feasible and effective technique for performing LAA occlusion in patients with thrombus within the LAA. This modification of the implantation technique may allow LAA closure indications to be extended to include patients with LAA thrombus, who were formerly considered unsuitable.