Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons.

Melanocortin 4 receptors (MC4Rs) in the central nervous system are key regulators of energy and glucose homeostasis. Notably, obese patients with MC4R mutations are hyperinsulinemic and resistant to obesity-induced hypertension. Although these effects are probably dependent upon the activity of the autonomic nervous system, the cellular effects of MC4Rs on parasympathetic and sympathetic neurons remain undefined. Here, we show that MC4R agonists inhibit parasympathetic preganglionic neurons in the brainstem. In contrast, MC4R agonists activate sympathetic preganglionic neurons in the spinal cord. Deletion of MC4Rs in cholinergic neurons resulted in elevated levels of insulin. Furthermore, re-expression of MC4Rs specifically in cholinergic neurons (including sympathetic preganglionic neurons) restores obesity-associated hypertension in MC4R null mice. These findings provide a cellular correlate of the autonomic side effects associated with MC4R agonists and demonstrate a role for MC4Rs expressed in cholinergic neurons in the regulation of insulin levels and in the development of obesity-induced hypertension.

Sudden cardiac death in adults with congenital heart disease: does QRS-complex fragmentation discriminate in structurally abnormal hearts?

Aims: Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients. Methods and results: From a multicentre cohort of 25 790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03). Conclusions: fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

Cardiac resynchronization therapy in adults with congenital heart disease.

Aims: In adults with congenital heart disease (CHD) heart failure is one of the leading causes of morbidity and mortality but experience with and reported outcome of cardiac resynchronization therapy (CRT) is limited. We investigated the efficacy of CRT in adults with CHD. Methods and results: This was a retrospective study including 48 adults with CHD who received CRT since 2003 in four tertiary referral centres. Responders were defined as patients who showed improvement in NYHA functional class and/or systemic ventricular ejection fraction by at least one category. Ventricular function was assessed by echocardiography and graded on a four point ordinal scale. Median age at CRT was 47 years (range 18-74 years) and 77% was male. Cardiac diagnosis included tetralogy of Fallot in 29%, (congenitally corrected) transposition of great arteries in 23%, septal defects in 25%, left sided lesions in 21%, and Marfan syndrome in 2% of the patients. The median follow-up duration after CRT was 2.6 years (range 0.1-8.8). Overall, 37 out of 48 patients (77%) responded to CRT either by improvement of NYHA functional class and/or systemic ventricular function. There were 11 non-responders to CRT. Of these, three patients died and four underwent heart transplantation. Conclusion: In this cohort of older CHD patients, CRT was accomplished with a success rate comparable to those with acquired heart disease despite the complex anatomy and technical challenges frequently encountered in this population. Further studies are needed to establish appropriate guidelines for patient selection and long term outcome.

Vasopressin V1a receptors mediate the hypertensive effects of [Pyr1 ]apelin-13 in the rat rostral ventrolateral medulla.

KEY POINTS: Dysfunctions in CNS regulation of arterial blood pressure lead to an increase in sympathetic nerve activity that participates in the pathogenesis of hypertension. The apelin-apelin receptor system affects arterial blood pressure homeostasis; however, the central mechanisms underlying apelin-mediated changes in sympathetic nerve activity and blood pressure have not been clarified. We explored the mechanisms involved in the regulation of [Pyr1 ]apelin-13-mediated cardiovascular control within the rostral ventrolateral medulla (RVLM) using selective receptor antagonists. We show that [Pyr1 ]apelin-13 acts as a modulating neurotransmitter in the normotensive RVLM to affect vascular tone through interaction with the vasopressin V1a receptor but that [Pyr1 ]apelin-13-induced sympathoexcitation is independent of angiotensin II receptor type 1, oxytocin, ionotropic glutamate and GABAA receptors. Our data confirm a role for the apelin peptide system in cardiovascular regulation at the level of the RVLM and highlight that this system is a possible potential therapeutic target for the treatment of hypertension. ABSTRACT: Apelin is a ubiquitous peptide that can elevate arterial blood pressure (ABP) yet understanding of the mechanisms involved remain incomplete. Bilateral microinjection of [Pyr1 ]apelin-13 into the rostral ventrolateral medulla (RVLM), a major source of sympathoexcitatory neurones, increases ABP and sympathetic nerve activity. We aimed to investigate the potential involvement of neurotransmitter systems through which the apelin pressor response may occur within the RVLM. Adult male Wistar rats were anaesthetized and ABP was monitored via a femoral arterial catheter. Bilateral RVLM microinjection of [Pyr1 ]apelin-13 significantly increased ABP (9 ± 1 mmHg) compared to saline (-1 ± 2mmHg; P < 0.001), which was blocked by pretreatment with the apelin receptor antagonist, F13A (0 ± 1 mmHg; P < 0.01). The rise in ABP was associated with an increase in the low frequency spectra of systolic BP (13.9 ± 4.3% total power; P < 0.001), indicative of sympathetic vasomotor activation. The [Pyr1 ]apelin-13-mediated pressor response and the increased low frequency spectra of systolic BP response were fully maintained despite RVLM pretreatment with the angiotensin II type 1 receptor antagonist losartan, the oxytocin receptor antagonist desGly-NH2 , d(CH2 )5 [D-Tyr2 ,Thr4 ]OVT, the ionotropic glutamate receptor antagonist kynurenate or the GABAA antagonist bicuculline (P > 0.05). By contrast, the [Pyr1 ]apelin-13 induced pressor and sympathoexcitatory effects were abolished by pretreatment of the RVLM with the vasopressin V1a receptor antagonist, SR 49059 (-1 ± 1 mmHg; 1.1 ± 1.1% total power, respectively; P < 0.001). These findings suggest that the pressor action of [Pyr1 ]apelin-13 in the RVLM of normotensive rats is not mediated via angiotensin II type 1 receptor, oxytocin, ionotropic glutamate or GABAA receptors but instead involves a close relationship with the neuropeptide modulator vasopressin.

Sudden cardiac death in adult congenital heart disease: can the unpredictable be foreseen?

AIMS: Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). Several risk factors for SCD including conduction disturbances and ventricular dysfunction have been described previously. However, electrocardiogram (ECG) and echocardiographic parameters may change over time, and the predictive value of such temporal changes, rather than their point estimates, for SCD remains unknown. METHODS AND RESULTS: This was a retrospective case-control study in adults with CHD and proven or presumed SCD and matched controls. Data were obtained from three databases including 25 000 adults with CHD. Sequential measurements were performed on electrocardiograms and echocardiograms. Ventricular function was assessed by echocardiography and graded on a four-point ordinal scale: 1, normal [ejection fraction (EF) ≥50%]; 2, mildly impaired (EF 40-49%); 3, moderately impaired (EF 30-39%); and 4, severely impaired (EF < 30%). Overall, 131 SCDs (mean age 36 ± 14 years, 67% male) and 260 controls (mean age 37 ± 13 years, 63% male) were included. At baseline, median QRS duration was 108 ms (range 58-168 ms) in SCDs and 97 ms (range 50-168 ms) in controls and increased over time at a rate of 1.6 ± 0.5 vs. 0.5 ± 0.2 ms/year in SCDs and controls, respectively (P = 0.011). QT dispersion at baseline was 61 ms (range 31-168 ms) in SCDs and 50 ms (range 21-129 ms) in controls. QT dispersion increased at a rate of 1.1 ± 0.4 ms/year in SCD victims and decreased at a rate of 0.2 ± 0.2 ms/year in controls (P = 0.004). Increase of QRS duration ≥5 ms/year was associated with an increased risk of SCD [OR 1.9, 95% confidence interval (CI) 1.1-3.3, P = 0.013]. Change from any baseline systemic ventricular function (normal, mild, or moderately impaired) to severe ventricular dysfunction over time was associated with the highest risk of SCD (OR 16.9, 95% CI 1.8-120.1, P = 0.008). CONCLUSION: In adults with CHD, QRS duration and ventricular dysfunction progress over time. Progression of QRS duration and the rate of impairment of ventricular function served to identify those at increased risk of SCD.

Bipolar ablation for deep intra-myocardial circuits: human ex vivo development and in vivo experience.

AIMS: Current conventional ablation strategies for ventricular tachycardia (VT) aim to interrupt reentrant circuits by creating ablation lesions. However, the critical components of reentrant VT circuits may be located at deep intramural sites. We hypothesized that bipolar ablations would create deeper lesions than unipolar ablation in human hearts. METHODS AND RESULTS: Ablation was performed on nine explanted human hearts at the time of transplantation. Following explant, the hearts were perfused by using a Langendorff perfusion setup. For bipolar ablation, the endocardial catheter was connected to the generator as the active electrode and the epicardial catheter as the return electrode. Unipolar ablation was performed at 50 W with irrigation of 25 mL/min, with temperature limit of 50°C. Bipolar ablation was performed with the same settings. Subsequently, in a patient with an incessant septal VT, catheters were positioned on the septum from both the ventricles and radiofrequency was delivered with 40 W. In the explanted hearts, there were a total of nine unipolar ablations and four bipolar ablations. The lesion depth was greater with bipolar ablation, 14.8 vs. 6.1 mm (P < 0.01), but the width was not different (9.8 vs. 7.8 mm). All bipolar lesions achieved transmurality in contrast to the unipolar ablations. In the patient with a septal focus, bipolar ablation resulted in termination of VT with no inducible VTs. CONCLUSION: By using a bipolar ablation technique, we have demonstrated the creation of significantly deeper lesions without increasing the lesion width, compared with standard ablation. Further clinical trials are warranted to detail the risks of this technique.

Sudden cardiac death in adult congenital heart disease.

BACKGROUND: Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. METHODS AND RESULTS: We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5-7.9; P=0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1-10.4; P=0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1-10.2; P=0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10-1.34; P=0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22-1.48; P=0.008). CONCLUSIONS: The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

Incidence and Clinical Predictors of Early and Late Complications of Implantable Cardioverter-Defibrillators in Adults With Congenital Heart Disease.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) has been proven to improve survival in adults with congenital heart disease (ACHD), but it is associated with a high rate of complications. We aimed to quantify the incidence of early (≤ 3 months; ECs) and late (> 3 months; LCs) complications in ACHD patients implanted with an ICD and to identify their clinical predictors. METHODS: We retrospectively reviewed 207 patients who had ICD follow-up at Toronto General Hospital from 1996 to 2019. RESULTS: The most common diagnoses were tetralogy of Fallot (32.4%), dextro-transposition of the great arteries (17.9%), and congenital corrected transposition of the great arteries (13%). No intraprocedural complications were observed. Median follow-up was 3.4 years (IQR 0.1-23). 24 patients (12%) developed EC (4 hematomas, 20 lead dislodgements). A total of 56 LCs occurred (46% lead failure, 21% infection, 11% prophylactic lead extraction, 9% neurologic pain, 9% erosion, 4% other) with an incidence rate of LCs of 18% per 5 person-years. Anatomic complexity (odds ratio 2.9; P = 0.02) and cardiac resynchronization therapy defibrillator implant (odds ratio 2.5; P = 0.04) were associated with ECs. Survival rates free from LCs were 92%, 86%, and 65%, respectively, after 1, 5, and 10 years. Presence of legacy leads (hazard ratio 2.9; P = 0.006) and subpulmonary ejection fraction (5% increase, hazard ratio 1.35; P = 0.031) were associated with LCs. CONCLUSIONS: ACHD patients at risk of sudden cardiac death continue to benefit from newer device technology. However, these patients, particularly those with greater anatomic and device complexity, remain at increased risk of developing complications over their lifetime. Given the life expectancy of this population, careful consideration needs to be given when a device for primary prevention is being contemplated.

LONEPINELLA SP. ISOLATED FROM WOUND INFECTIONS OF KOALAS.

We describe two cases of wound infections of koalas (Phascolarctos cinereus), one wild and one captive, in which Lonepinella-like organisms were involved. The wild adult koala was captured with bite wound injuries, as part of a koala population management program in Queensland, Australia. In both cases, there was evidence of physical trauma causing the initial wound. The captive koala suffered injury from the cage wire, and the wild koala had injuries suggestive of intermale fighting. Gram-negative bacteria isolated from both cases proved to be challenging to identify using routine diagnostic tests. The wound in the captive koala yielded a pure culture of an organism shown by whole genome sequence (WGS) analysis to be a member of the genus Lonepinella, but not a member of the only formally described species, L. koalarum. The wound of the wild koala yielded a mixed culture of Citrobacter koseri, Enterobacter cloacae and an organism shown by WGS analysis to be Lonepinella, but again not Lonepinella koalarum. Both cases were difficult to treat; the captive koala eventually had to have the phalanges amputated, and the wild koala required removal of the affected claw. The two Lonepinella isolates from these cases have a close relationship to an isolate from a human wound caused by a koala bite and may represent a novel species within the genus Lonepinella. Wound infections in koalas linked to Lonepinella have not been reported previously. Wildlife veterinarians need to be aware of the potential presence of Lonepinella-like organisms when dealing with wound infections in koalas, and the inability of commercial kits and systems to correctly identify the isolates.

Striking In vivo phenotype of a disease-associated human SCN5A mutation producing minimal changes in vitro.

BACKGROUND: The D1275N SCN5A mutation has been associated with a range of unusual phenotypes, including conduction disease and dilated cardiomyopathy, as well as atrial and ventricular tachyarrhythmias. However, when D1275N is studied in heterologous expression systems, most studies show near-normal sodium channel function. Thus, the relationship of the variant to the clinical phenotypes remains uncertain. METHODS AND RESULTS: We identified D1275N in a patient with atrial flutter, atrial standstill, conduction disease, and sinus node dysfunction. There was no major difference in biophysical properties between wild-type and D1275N channels expressed in Chinese hamster ovary cells or tsA201 cells in the absence or presence of ß1 subunits. To determine D1275N function in vivo, the Scn5a locus was modified to knock out the mouse gene, and the full-length wild-type (H) or D1275N (DN) human SCN5A cDNAs were then inserted at the modified locus by recombinase mediated cassette exchange. Mice carrying the DN allele displayed slow conduction, heart block, atrial fibrillation, ventricular tachycardia, and a dilated cardiomyopathy phenotype, with no significant fibrosis or myocyte disarray on histological examination. The DN allele conferred gene-dose-dependent increases in SCN5A mRNA abundance but reduced sodium channel protein abundance and peak sodium current amplitudes (H/H, 41.0±2.9 pA/pF at -30 mV; DN/H, 19.2±3.1 pA/pF, P<0.001 vs. H/H; DN/DN, 9.3±1.1 pA/pF, P<0.001 versus H/H). CONCLUSIONS: Although D1275N produces near-normal currents in multiple heterologous expression experiments, our data establish this variant as a pathological mutation that generates conduction slowing, arrhythmias, and a dilated cardiomyopathy phenotype by reducing cardiac sodium current.

Evolving electroanatomic substrate and intra-atrial reentrant tachycardia late after Fontan surgery.

INTRODUCTION: The prevalence of intra-atrial reentrant tachycardia (IART) increases with age in Fontan patients. This study aimed to characterize the atrial electroanatomic substrate for IART late after Fontan surgery. METHODS AND RESULTS: Detailed electroanatomic mapping of the right atrium (RA) was performed in 11 consecutive patients (33 ± 9 years) with older style Fontan circulation (atriopulmonary and atrioventricular connection) who underwent their first radiofrequency catheter ablation (RFCA) for IART. A comparative group of 30 non-Fontan congenital heart disease (CHD) patients were also studied. Fontan patients had larger RA (P = 0.004), larger low-voltage area ≤ 0.5 mV (P = 0.01), and more fractionated potentials (P < 0.001) than non-Fontan CHD patients. RA enlargement correlated significantly with both low-voltage zones (Spearman ρ= 0.68, P < 0.001) and fractionated potentials (Spearman ρ= 0.48, P = 0.001). Among Fontan patients, both age and time since Fontan surgery were significantly correlated to the amount of low-voltage areas (Spearman ρ= 0.87, P < 0.001; Spearman ρ= 0.63, P = 0.04, respectively). Successful RFCA was accomplished in 30 (73%) patients and was less likely in Fontan patients (54% vs 83%, P = 0.04). Larger RA was significantly associated with a lower success rate (P = 0.04). During a follow-up duration of 2.3 ± 1.6 years, IART recurred in 47% of patients. Larger RA size and larger low-voltage areas predicted IART recurrence after RFCA. CONCLUSION: Fontan patients demonstrate progressive adverse atrial electrical remodeling with increasing age and time since surgery. Newer strategies beyond surgical incisions, such as pharmacotherapies that retard the progression of atrial fibrosis, may be required to reduce the long-term risk of atrial arrhythmias.

A randomized controlled trial of cognitive behavior therapy tailored to psychological adaptation to an implantable cardioverter defibrillator.

OBJECTIVES: To evaluate a eight-session cognitive behavior therapy (CBT) intervention tailored to adaptation in implantable cardioverter defibrillator (ICD) patients; and to test for treatment group by gender interaction effects. METHODS: Patients receiving their first ICD implant were randomized to CBT or usual cardiac care. Primary outcomes measured at baseline, 6-month, and 12-month follow-ups were symptoms of anxiety and depression (Hospital Anxiety and Depression Scale), posttraumatic stress disorder symptoms (Impact of Events Scale-Revised), and phobic anxiety (Crown-Crisp Experiential Index). Secondary outcomes were quality of life (Short Form-36 Physical Component Summary and Short Form-36 Mental Component Summary) and ICD shocks or antitachycardia pacing therapies. RESULTS: Of 292 eligible patients, 193 consented and were randomized to CBT (n = 96) or usual cardiac care (n = 97). Eighty percent were male; mean age was 64.4 years (standard deviation = 14.3); and 70% received an ICD for secondary prevention. No baseline differences were observed between the treatment conditions; however, women scored worse than men on all psychological and quality of life variables (p < .05). Eighty-three percent completed follow-up. Repeated-measures analyses of covariance revealed significantly greater improvement with CBT on posttraumatic stress disorder total and avoidance symptoms for men and women combined (p < .05) and significantly greater improvement in depressive symptoms and Short Form-36 Mental Component Summary only in women (p < .01). No differences were observed between treatment conditions on ICD therapies over follow-up. CONCLUSION: A CBT intervention to assist adaptation to an ICD enhanced psychological functioning over the first year post implant.

Pulmonary valve replacement in adults with repaired tetralogy of Fallot.

There is a growing population of young adults with tetralogy of Fallot. Although surgical approaches have evolved, many adults with repaired tetralogy of Fallot have been left with residual pulmonary regurgitation. Pulmonary regurgitation is an important contributor to a number of late complications including exercise limitations, right heart failure, arrhythmia, and sudden death. Because bioprosthetic valves are used in this population, clinicians must weigh the beneficial effects of pulmonary valve replacement against the associated risks, including subsequent re-operation. In this review, we will appraise the evidence supporting pulmonary valve replacement in the adult with repaired tetralogy of Fallot, as well as the optimal timing and mode of intervention.

Outcomes in Young Adults With Tetralogy of Fallot and Pulmonary Annular Preserving or Transannular Patch Repairs.

BACKGROUND: Early surgical tetralogy of Fallot (ToF) repair involved patching across the pulmonic annulus (transannular patch [TAP] repair), which resulted in severe pulmonic regurgitation. Long-term outcome improvements were anticipated with modifications that preserved the pulmonic annulus (annulus-preserving [AP] repair). The objective of the present study was to evaluate the need for late reintervention in adults with AP repair and those with TAP repair. METHODS: We conducted a retrospective review of adults (born 1981-1996) with childhood intracardiac ToF repairs at a tertiary care center. The primary cardiovascular outcome was need for reintervention after primary intracardiac repair of ToF. Secondary outcomes included a composite of death, heart failure, and ventricular arrhythmias. RESULTS: Two hundred thirty adults were included: 104 with AP repair and 126 with TAP repair. The median age at last follow up was 25 years (interquartile range [IQR] 20-28) and the median follow-up duration was 7.9 years (IQR 3.5-12). Reintervention of any type was significantly more common in the TAP group during both childhood and adulthood (72.2% TAP vs 20.2% AP, HR 5.5, 95% CI 3.4-9.0; P < 0.001). Pulmonary valve replacement (PVR) was almost 6 times more likely in adults with TAP repair (65.1% TAP vs 16.3% AP, HR 5.7, 95% CI 3.4-9.7; P < 0.001). CONCLUSIONS: Patients who had AP ToF repair had significantly fewer late reinterventions compared with TAP repair, with the majority of reinterventions due to PVR. More long-term follow-up is required.

Safety and Long-term Outcomes of Defibrillator Therapy in Patients With Right-Sided Implantable Cardiac Devices in Adults With Congenital Heart Disease.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have been proven to prevent sudden cardiac death in adult congenital heart disease (ACHD) patients. Although the left side is chosen by default, implantation from the right side is often required. However, little is known about the efficacy and safety of right-sided ICDs in ACHD patients. METHODS: In this study we reviewed a total of 191 ACHD patients undergoing ICD/cardioverter resynchronisation therapy-defibrillator (CRT-D) implantation at our hospital between 2001 and 2019 (134 men and 57 women; age [mean ± standard deviation], 41.5 ± 14.8 years). RESULTS: Twenty-seven patients (14.1%) had right-sided devices. The most common causes of right-sided implantation were persistent left superior vena cava and vein occlusion (37.0%). Although procedure time (202.8 ± 60.5 minutes vs 143.8 ± 69.1 minutes, P = 0.008) was longer and the procedural success was lower (92.6% vs 99.4%, P = 0.008) for right-sided devices, no difference in R-wave and pacing threshold were noted. Among the 47 patients (24.6%) who underwent defibrillation threshold testing (DFT), no difference in DFT was observed (25.2 ± 5.3 J vs 23.8 ± 4.1 J, P = 0.460). During the median follow-up of 42.4 months, appropriate ICD therapy was observed in 5 (18.5%) and 30 (18.3%) patients for right- and left-sided ICDs/CRTDs, respectively (P = 0.978). No significant difference was seen in complications between them. CONCLUSIONS: Implantation of an ICD on the right side is technically challenging, but it is feasible as an alternative approach for ACHD patients with contraindications to left-sided device implantation.

Impact of Catheter Ablation for Atrial Arrhythmias on Repeat Cardioversion in Adults With Congenital Heart Disease.

BACKGROUND: Atrial tachyarrhythmias (AAs) are the main source of morbidity and mortality in adult congenital heart disease (ACHD). Direct-current cardioversion (DCCV) is an effective method to acutely terminate AAs, but many patients require repeated DCCV. Little is known about the impact of radiofrequency catheter ablation (RFCA) of AAs on the incidence of repeated DCCV in patients with ACHD. The purpose of this study was to evaluate the impact of RFCA on the incidence of DCCV in patients with ACHD. METHODS: A total of 157 patients with ACHD undergoing DCCV in our hospital from 2011 to 2018 (female n = 76 [48.4%], mean age 37.8 ± 12.5 y), were reviewed. The median follow-up period was 31.8 months (interquartile range 16.3-55.1 mo). RESULTS: Out of the total of 157 patients, 102 (65.0%) underwent RFCA for AAs, and 55 (35.0%) were treated without RFCA. Successful RFCA with termination of AAs during ablation was 62.7%. More than one-half of the patients had complex forms of CHD (62.4%). During follow-up, 57 patients (55.9%) who had RFCA developed recurrence of AAs, and 36 patients (35.2%) underwent repeated DCCV. Thirty-three (60.0%) out of 55 patients without RFCA required repeated cardioversion. Compared with patients without RFCA, RFCA significantly reduced the need for repeated DCCV by 40% (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.23-0.80; P = 0.009). In multivariate analysis, successful RFCA was associated with reduced risk of DCCV (HR 0.41, 95% CI 0.19-0.92; P = 0.031). CONCLUSIONS: AAs remain common despite RFCA in patients with ACHD. Nevertheless, RFCA is associated with a marked reduction in the need for repeated DCCV.

Role of amiodarone in the management of atrial arrhythmias in adult Fontan patients.

BACKGROUND: Patients with Fontan circulation are known to be at high risk for developing atrial tachyarrhythmias (AAs). Our objective was to examine the efficacy and safety of amiodarone in the management of ATs in adult Fontan patients. METHODS: Primary outcomes of this single-centre, retrospective study included freedom from AAs and incidence of adverse effects of amiodarone on Fontan patients. Heart failure (HF) events and composite outcomes of death from any cause, Fontan revision and heart transplantation were evaluated as secondary outcomes. Predictors of HF and discontinuing amiodarone were also evaluated. RESULTS: A total of 61 patients (mean age 31.6±11.3 years, 40.9% female), who were treated with amiodarone in between 1995 and 2018, were included. AAs free survival at 1, 3 and 5 years were 76.2%, 56.9% and 30.6%, respectively. During a median follow-up of 50.5 months, 34 (55.7%) patients developed side effects, and 20 (32.8%) patients discontinued amiodarone due to side effects. Thyroid dysfunction was the most common side effect (n=26, 76.5%), amiodarone-induced thyrotoxicosis (AIT) (n=16, 27.1%) being most common thyroid dysfunction. Young age (age <28.5 years) was associated with discontinuing amiodarone (HR 5.50, 95% CI 1.19 to 25.4, p=0.029). AIT significantly increased risk of HF (HR 4.82, 95% CI 1.71 to 13.6, p=0.003). CONCLUSIONS: Short-term efficacy of amiodarone in Fontan physiology is acceptable. However, long-term administration is associated with a reduction of efficacy and a significant prevalence of non-cardiac side effects. AIT is associated with exacerbation of HF. The judicious use of amiodarone administration should be considered in this population.

Identification of patients at risk of sudden cardiac death in congenital heart disease: The PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD).

BACKGROUND: Sudden cardiac death (SCD) is the main preventable cause of death in patients with adult congenital heart disease (ACHD). Since robust risk stratification methods are lacking, we developed a risk score model to predict SCD in patients with ACHD: the PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD) risk score model. OBJECTIVE: The purpose of this study was to prospectively study predicted SCD risk using the PREVENTION-ACHD risk score model and actual SCD and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) rates in patients with ACHD. METHODS: The PREVENTION-ACHD risk score model assigns 1 point each to coronary artery disease, New York Heart Association class II/III heart failure, supraventricular tachycardia, systemic ejection fraction < 40%, subpulmonary ejection fraction < 40%, QRS duration ≥ 120 ms, and QT dispersion ≥ 70 ms. SCD risk was calculated for each patient. An annual predicted risk of ≥3% constituted high risk. The primary outcome was SCD or VT/VF after 2 years. The secondary outcome was SCD. RESULTS: The study included 783 consecutive patients with ACHD (n=239 (31%) left-sided lesions; n=138 (18%) tetralogy of Fallot; n=108 (14%) closed atrial septal defect; median age 36 years; interquartile range 28-47 years; n=401 (51%) men). The PREVENTION-ACHD risk score model identified 58 high-risk patients. Eight patients (4 at high risk) experienced the primary outcome. The Kaplan-Meier estimates were 7% (95% confidence interval [CI] 0.1%-13.3%) in the high-risk group and 0.6% (95% CI 0.0%-1.1%) in the low-risk group (hazard ratio 12.5; 95% CI 3.1-50.9; P < .001). The risk score model's sensitivity was 0.5 and specificity 0.93, resulting in a C-statistic of 0.75 (95% CI 0.57-0.90). The hazard ratio for SCD was 12.4 (95% CI 1.8-88.1) (P = .01); the sensitivity and specificity were 0.5 and 0.92, and the C-statistic was 0.81 (95% CI 0.67-0.95). CONCLUSION: The PREVENTION-ACHD risk score model provides greater accuracy in SCD or VT/VF risk stratification as compared with current guideline indications and identifies patients with ACHD who may benefit from preventive implantable cardioverter-defibrillator implantation.