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.

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.

The Role of Ablation in Prevention of Recurrent Implantable Cardioverter Defibrillator Shocks in Patients With Tetralogy of Fallot.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are effective in preventing arrhythmic sudden cardiac death in patients with tetralogy of Fallot (TOF). Although ICD therapies for malignant ventricular arrhythmias can be life-saving, shocks could have deleterious consequences. Substrate-based ablation therapy has become the standard of care to prevent recurrent ICD shocks in patients with ischemic cardiomyopathy. However, the efficacy and safety of this invasive therapy in the prevention of recurrent ICD shocks in patients with TOF has not been well evaluated. METHODS: Records of a total of 47 consecutive TOF patients (mean age: 43.1 ± 13.2 years, male sex: n = 34 [72.3%]) who underwent ICD implantation for secondary prevention between 2000 and 2018 were reviewed. RESULTS: Twenty (42.6%) patients underwent invasive therapy (radiofrequency catheter ablation, n = 8; surgical ablation with pulmonary valve replacement, n = 12) before ICD implantation. Twenty-seven patients (57.4%) were managed noninvasively. During follow-up (median 80.5 [interquartile range, 28.5-131.0] months), 2 (10.0%) patients in the invasive group and 10 (37.0%) patients in the noninvasive group received appropriate ICD shocks (P = 0.036). Logistic regression analysis showed that invasive therapy was associated with a decreased risk of ICD shocks by 81.1% (odds ratio, 0.189; 95% confidence interval, 0.036-0.990; P = 0.049). Furthermore, invasive therapy was associated with decreased risk of the composite outcomes of ICD shock, death, cardiac transplantation, and hospital admission (odds ratio, 0.090; 95% confidence interval, 0.025-0.365; P = 0.013) compared with noninvasive therapy. CONCLUSIONS: Invasive substrate modification therapy was associated with a lower likelihood of ICD shocks and improvement of long-term outcomes in TOF patients.

CONTEXTE: Les défibrillateurs cardioverteurs implantables (DCI) sont efficaces pour prévenir la mort cardiaque subite provoquée par une arythmie chez les patients présentant une tétralogie de Fallot (TF). Bien que le traitement des arythmies ventriculaires malignes par DCI puisse sauver des vies, les chocs administrés peuvent avoir des conséquences délétères. L'ablation du substrat est devenue le traitement de référence pour prévenir l'administration à répétition de chocs par DCI chez les patients atteints d'une cardiomyopathie ischémique. L'efficacité et l'innocuité de ce traitement invasif pour prévenir l'administration de chocs répétés chez les patients présentant une TF n'ont toutefois pas été bien évaluées. MÉTHODOLOGIE: Nous avons examiné les cas consécutifs de 47 patients présentant une TF (âge moyen : 43,1 ± 13,2 ans; hommes : n = 34 [72,3 %]) ayant reçu un DCI en prévention secondaire entre 2000 et 2018. RÉSULTATS: Au total, 20 (42,6 %) patients ont subi un traitement invasif (ablation par cathéter par radiofréquence, n = 8; ablation chirurgicale et remplacement de la valve pulmonaire, n = 12) avant l'implantation d'un DCI. Vingt-sept patients (57,4 %) ont été pris en charge de façon non invasive. Au cours de la période de suivi (durée médiane de 80,5 [intervalle interquartile : 28,5 à 131,0] mois), 2 (10,0 %) patients du groupe ayant subi une intervention invasive et 10 (37,0 %) patients du groupe ayant subi une intervention non invasive ont reçu un choc approprié par DCI (p = 0,036). Les résultats de l'analyse par régression logistique montrent que le traitement invasif est associé à une réduction du risque de choc par DCI de 81,1 % (rapport des cotes : 0,189; intervalle de confiance à 95 % : de 0,036 à 0,990; p = 0,049). En outre, le traitement invasif est associé à une réduction du risque de survenue d'un des événements du paramètre d'évaluation composé, soit un choc administré par DCI, le décès, une transplantation cardiaque ou une hospitalisation (rapport des cotes : 0,090; intervalle de confiance à 95 % : de 0,025 à 0,365; p = 0,013) par rapport au traitement non invasif. CONCLUSIONS: La modification invasive du substrat a été associée à une probabilité plus faible de choc administré par DCI et à une amélioration des résultats à long terme chez les patients présentant une TF.

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.

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.

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.

Lateral tunnel Fontan atrial tachycardia ablation trans-baffle access is not mandatory as the initial strategy.

BACKGROUND: Mapping and ablation of atrial tachycardia (AT) is commonly performed in lateral tunnel Fontan (LTF) patients, yet there is little information on the need of baffle puncture to access the pulmonary venous atrium (PVA). This study aimed to evaluate the most common chamber location of critical sites for majority of AT in LTF patients. METHODS: Consecutive LTF patients underwent catheter-based high-density mapping and ablation of AT from Nov. 2015 to Mar. 2019. Critical sites were identified by a combination of activation and entrainment mapping. Acute procedural success was defined as AT termination with ablation and non-inducibility of any AT. Predictors for ablation failure were evaluated in retrospect. RESULTS: Fifteen catheter ablation procedures were performed in 9 patients. A total of 15 clinical ATs (mean TCL 369 ± 91 ms) were mapped. The mechanism was macro re-entry in 11 (73%) and micro re-entry in 2. In 11 ATs (73%), 94 ± 5% of tachycardia cycle length (TCL) were mapped inside the tunnel. The commonest site of successful ablation in the tunnel was on the lateral wall (60%). Trans-baffle access was obtained during 5 of 15 procedures (33%). Overall, procedural success was achieved in 9 of 15 procedures (60%). There were no complications. Recurrence of AT was 42% over a follow-up period of 4.3 ± 3.2 years. Faster TCL of 200-300 ms showed a trend towards ablation failure, (OR 17, 95% CI 0.7 to 423, p = 0.08). CONCLUSIONS: Catheter ablation can be performed effectively for ATs in LTF patients usually from inside the tunnel. ATs with critical sites in the PVA are uncommon. This information will help plan ablation in LTF patients without resorting to initial trans-baffle access.

Prolonged Tpeak -Tend interval is a risk factor for sudden cardiac death in adults with congenital heart disease.

OBJECTIVE: Adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). However, methods for risk stratification are not yet well-defined. The Tpeak -Tend (TpTe) interval, a measure of dispersion of ventricular repolarization, is a risk factor for SCD in non-ACHD patients. We aim to evaluate whether TpTe can be used in risk stratification for SCD in ACHD patients. DESIGN: From an international multicenter cohort of 25 790 ACHD patients, we identified all SCD cases. Cases were matched to controls by age, gender, congenital defect, and (surgical) intervention. OUTCOME MEASURES: TpTe was measured on a standard 12-lead ECG. The maximum TpTe of all ECG leads (TpTe-max), mean (TpTe-mean), and TpTe dispersion (maximum minus minimum) were obtained. Odds ratios (OR) for SCD cases vs controls were calculated using conditional logistic regression analysis. RESULTS: ECGs were available for 147 cases (median age at death 33.5 years (quartiles 26.2, 48.7), 66% male) and 267 controls. The mean TpTe-max was 97 ± 24 ms in cases vs 84 ± 17 ms in controls (P < .001); TpTe-mean was 70 ± 16 vs 63 ± 10 ms (P < .001); and dispersion was 51 ± 22 ms vs 41 ± 16 ms (P = .02), respectively. Assessing each ECG lead separately, TpTe in lead aVR predicted SCD most accurately. TpTe in lead aVR was 71 ± 23 ms in cases vs 61 ± 13 ms in controls (P < .001). After adjusting for impaired ventricular function, heart failure symptoms, and prolonged QRS duration, the OR of SCD of TpTe in lead aVR at an optimal cutoff of 80 ms was 5.8 (95% CI 2.7-12.4, P < .001). CONCLUSIONS: The TpTe interval is associated with SCD in ACHD patients. Particularly, TpTe in lead aVR can be used as an independent risk factor for SCD in ACHD patients and may, therefore, add precision to current risk prediction models.

Novel insights into pasteurellosis in captive pinnipeds.

Pasteurella multocida is a heterogeneous bacterium, which has the capacity to cause disease in a wide range of host species and is also recognized as an important zoonotic pathogen. Two sequential deaths in captive fur seals occurred at Sea World, Australia during December 2017. A fibrinosuppurative bronchopneumonia in a Subantarctic fur seal (Arctocephalus tropicalis) resulted in death within 24 h of nonspecific signs of illness, whereas a septic peritonitis in a New Zealand fur seal (Arctocephalus forsteri) resulted in death within 12 h of clinical presentation. The cases happened within three days in two different pool locations, although both had previously been housed in the same area. A total of six Pasteurella multocida isolates were obtained from several internal organs at necropsy in both cases and were subjected to whole genome sequencing and phylogenomic analysis. In-silico typing of the isolates revealed that all belonged to Multi-Locus Sequence Type 7 and carried lipopolysaccharide outer core biosynthesis loci Type 3. Phylogenomic analysis of the isolates confirmed that the isolates were near identical at the core genome level, suggesting acquisition from a common source. The results also revealed the presence of within host and across animal diversity of P. multocida isolates for the first time even in a clearly connected outbreak.

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.

Prevention of Sudden Cardiac Death in Adults With Congenital Heart Disease: Do the Guidelines Fall Short?

BACKGROUND: Sudden cardiac death (SCD) is a major cause of mortality in adult congenital heart disease (ACHD) patients. SCD may be prevented by implantable cardioverter-defibrillator (ICD) implantation, but patient stratification remains troublesome. The 2014 Consensus Statement on Arrhythmias in ACHD patients and the 2015 European Society of Cardiology Guidelines specified recommendations for ICD implantation in ACHD patients for the first time. We assess the discriminative ability of these ICD recommendations for SCD in ACHD patients. METHODS AND RESULTS: Of 25 790 ACHD patients in an international multicenter registry, we identified all SCD cases, matched to living controls by age, sex, congenital defect, and surgical repair. We assessed all primary prevention ICD recommendations listed in both documents. We used conditional logistic regression models to calculate odds ratios and receiver operating characteristic curves with area under the curve. Consensus Statement: One hundred twenty-four cases (median age at death, 33 years [26-44]; 67% men) and 230 controls were studied. In total, 41% of SCD cases and 17% of controls had an ICD recommendation (odds ratio, 5.9; P<0.001). European Society of Cardiology Guidelines: Of one hundred fifty-seven cases (median age at death, 33 years [26-48]; 64% men) and 292 controls, 35% and 14% had an ICD recommendation, respectively (odds ratio, 4.8; P<0.001). CONCLUSIONS: A minority of SCD cases had an ICD recommendation according to these guidelines, whereas the majority of SCD victims remained unrecognized. With an area under the curve of 0.6 to 0.7, the discriminative ability of both guidelines was mediocre. Critical clinical reasoning when deciding on ICD implantation in ACHD patients, therefore, remains vital.

Atrial tachyarrhythmia in adult congenital heart disease.

The adult congenital heart disease (ACHD) population continues to grow and most cardiologists, emergency room physicians and family doctors will intermittently come into contact with these patients. Oftentimes this may be in the setting of a presentation with atrial tachyarrhythmia; one of the commonest late complications of ACHD and problem with potentially serious implications. Providing appropriate initial care and ongoing management of atrial tachyarrhythmia in ACHD patients requires a degree of specialist knowledge and an awareness of certain key issues. In ACHD, atrial tachyarrhythmia is usually related to the abnormal anatomy of the underlying heart defect and often occurs as a result of surgical scar or a consequence of residual hemodynamic or electrical disturbances. Arrhythmias significantly increase mortality and morbidity in ACHD and are the most frequent reason for ACHD hospitalization. Intra-atrial reentrant tachycardia and atrial fibrillation are the most prevalent type of arrhythmia in this patient group. In hemodynamically unstable patients, urgent cardioversion is required. Acute management of the stable patient includes anticoagulation, rate control, and electrical or pharmacological cardioversion. In ACHD, rhythm control is the preferred management strategy and can often be achieved. However, in the long-term, medication side-effects can prove problematic. Electrophysiology studies and catheter ablation are important treatments modalities and in certain cases, surgical or percutaneous treatment of the underlying cardiac defect has a role. ACHD patients, especially those with complex CHD, are at increased risk of thromboembolic events and anticoagulation is usually required. Female ACHD patients of child bearing age may wish to pursue pregnancies. The risk of atrial arrhythmias is increased during pregnancy and management of atrial tachyarrhythmia during pregnancy needs specific consideration.

Ventricular Arrhythmias in Adult Congenital Heart Disease: Mechanisms, Diagnosis, and Clinical Aspects.

The risk of ventricular arrhythmias in the adult congenital heart disease population increases with age. The mechanism, type, and frequency vary depending on the complexity of the defect, whether it has been repaired, and the type and timing of repair. Risk stratification for sudden death in patients with congenital heart disease is often challenging. Current recommendations provide a useful guide for management of these patients and risk stratification continues to evolve. Internal cardiac defibrillator implantation is often challenging due to limited transvenous access, often resulting in the need for epicardial or subcutaneous devices.

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.

T-Wave Morphology Analysis in Congenital Long QT Syndrome Discriminates Patients From Healthy Individuals.

OBJECTIVES: This study aims to assess the capability of T-wave analysis to: 1) identify genotype-positive long QT syndrome (LQTS) patients; 2) identify LQTS patients with borderline or normal QTc interval (≤460 ms); and 3) classify LQTS subtype. BACKGROUND: LQTS often presents with a nondiagnostic electrocardiogram (ECG). T-wave abnormalities may be the only marker of this potentially lethal arrhythmia syndrome. METHODS: ECGs taken at rest in 108 patients (43 with LQTS1, 20 with LQTS2, and 45 control subjects) were evaluated for T-wave flatness, asymmetry, and notching, which produces a morphology combination score (MCS) of the 3 features (MCS = 1.6 × flatness + asymmetry + notch) using QT Guard Plus Software (GE Healthcare, Milwaukee, Wisconsin). To assess for heterogeneity of repolarization, the principal component analysis ratio 2 (PCA-2) was calculated. RESULTS: Mean QTc intervals were 486 ± 50 ms (LQTS1), 479 ± 36 ms (LQTS2), and 418 ± 24 ms (control subjects) (p < 0.05). MCS and PCA-2 differed between LQTS patients and control subjects (MCS: 117.8 ± 57.4 vs. 71.9 ± 16.2; p < 0.001; PCA-2: 20.2 ± 10.4% vs. 14.6 ± 5.5%; p < 0.001), LQTS1 and LQTS2 patients (MCS: 96.3 ± 28.7 vs. 164 ± 75.2; p < 0.001; PCA-2: 17.8 ± 8.3% vs. 25 ± 12.6%; p < 0.001), and between LQTS patients with borderline or normal QTc intervals (n = 17) and control subjects (MCS: 105.7 ± 49.9 vs. 71.9 ± 16.2; p < 0.001; PCA-2: 18.1 ± 7.2% vs. 14.6 ± 5.5%; p < 0.001). T-wave metrics were consistent across multiple ECGs from individual patients based on the average intraclass correlation coefficient (MCS: 0.96; PCA-2: 0.86). CONCLUSIONS: Automated T-wave morphology analysis accurately discriminates patients with pathogenic LQTS mutations from control subjects and between the 2 most common LQTS subtypes. Mutation carriers without baseline QTc prolongation were also identified. This may be a useful tool for screening families of LQTS patients, particularly when the QTc interval is subthreshold and genetic testing is unavailable.