Noninvasive ECG imaging of the intrinsic atrial pacemaker and atrial activation in surgically repaired or palliated congenital heart disease.

INTRODUCTION: Sinus node location, function, and atrial activation are often abnormal in patients with congenital heart disease (CHD), due to anatomical, surgical, and acquired factors. We aimed to perform noninvasive electrocardiographic imaging (ECGI) of the intrinsic atrial pacemaker and atrial activation in patients with surgically repaired or palliated CHD, compared with control patients with structurally normal hearts. METHODS AND RESULTS: Atrial ECGI was performed in eight CHD patients with prespecified diagnoses (Fontan circulation, dextro transposition of the great arteries post Mustard/Senning, tetralogy of Fallot), and three controls. Activation and propagation maps were constructed in presenting rhythm. Wavefront propagation was analyzed to identify (1) intrinsic atrial pacemaker breakout site, (2) morphological right atrial (RA) activation pattern, (3) morphological left atrial (LA) breakout sites (i.e., interatrial connections), (4) LA activation pattern, and (5) putative lines of block. Physiologically appropriate atrial activation and propagation maps were able to be constructed. In the majority of patients, atrial breakouts were in keeping with the sinus node, observed in a crescent-shaped distribution from the anterior superior vena cava to the posterior RA. Ectopic atrial pacemaker sites were demonstrated in the atriopulmonary (AP) Fontan patient (very diffuse posterolateral RA) and Mustard patient (very posterior RA competing with a low RA focus). RA propagation was laminar in controls, but suggested either a line of block or conduction slowing consistent with an atriotomy scar in the tetralogy of Fallot (TOF) patients. Putative lines of block were more complex and RA propagation more abnormal in the atrial switch and AP Fontan patients, compared with the TOF patients. RA activation in the extracardiac Fontan patients was relatively laminar. Earliest LA breakout was most commonly observed in the region of Bachmann's Bundle in both controls and CHD patients, except for posterior LA breakouts in two patients. LA activation was typically more homogeneous than RA activation in CHD patients. CONCLUSION: ECGI can be utilized to create a noninvasive mapping model of atrial activation in postsurgical CHD, demonstrating atrial pacemaker location, putative lines of block and interatrial connections. Once validated invasively, this may have clinical implications in predicting risk of sinus node dysfunction and atrial arrhythmias, or in guiding catheter ablation.

His bundle combined with deep septal left bundle branch area pacing for atrial fibrillation prior to atrioventricular node ablation.

Background: To mitigate the risk of dyssynchrony-induced cardiomyopathy, international guidelines advocate His bundle pacing (HBP) with a ventricular backup lead prior to atrioventricular node ablation in treatment-refractory atrial fibrillation and normal left ventricular ejection fraction. As a result of concerns with long-term pacing parameters associated with HBP, this case series reports an adopted strategy of HBP combined with deep septal left bundle branch area pacing (dsLBBAP) in this patient cohort, enabling intrapatient comparison of the two pacing methods. Methods and Results: Eight patients aged 72 ± 10 years (left ventricular ejection fraction 53 ± 4%) underwent successful combined HBP and dsLBBAP implant prior to AV node ablation. Intrinsic QRS duration was 118 ± 46 ms. When compared to dsLBBAP, HBP had lower sensed ventricular amplitude (2.4 ± 1.1 vs. 15 ± 5.3 V, p = .001) and lower lead impedance (522 ± 57 vs. 814 ± 171ohms, p = .02), but shorter paced QRS duration (101 ± 20 vs. 119 ± 17 ms, p = .02). HBP pacing threshold was 1.0 ± 0.6 V at 1 ms pulse width, and dsLBBAP pacing threshold was 0.5 ± 0.2 V at 0.4 ms pulse width. Five patients underwent cardiac CT showing adequate dsLBBAP ventricular septal penetration (8.6 ± 1.3 mm depth, 2.4 ± 0.5 mm distance from left ventricular septal wall). No complications occurred during a mean follow-up duration of 121 ± 92 days. Conclusions: Combined HBP and dsLBBAP pacing is a feasible approach as a pace and ablate strategy for atrial fibrillation refractory to medical therapy.

Higher power short duration vs. lower power longer duration posterior wall ablation for atrial fibrillation and oesophageal injury outcomes: a prospective multi-centre randomized controlled study (Hi-Lo HEAT trial).

AIMS: Radiofrequency (RF) ablation for pulmonary vein isolation (PVI) in atrial fibrillation (AF) is associated with the risk of oesophageal thermal injury (ETI). Higher power short duration (HPSD) ablation results in preferential local resistive heating over distal conductive heating. Although HPSD has become increasingly common, no randomized study has compared ETI risk with conventional lower power longer duration (LPLD) ablation. This study aims to compare HPSD vs. LPLD ablation on ETI risk. METHODS AND RESULTS: Eighty-eight patients were randomized 1:1 to HPSD or LPLD posterior wall (PW) ablation. Posterior wall ablation was 40 W (HPSD group) or 25 W (LPLD group), with target AI (ablation index) 400/LSI (lesion size index) 4. Anterior wall ablation was 40-50 W, with a target AI 500-550/LSI 5-5.5. Endoscopy was performed on Day 1. The primary endpoint was ETI incidence. The mean age was 61 ± 9 years (31% females). The incidence of ETI (superficial ulcers n = 4) was 4.5%, with equal occurrence in HPSD and LPLD (P = 1.0). There was no difference in the median value of maximal oesophageal temperature (HPSD 38.6°C vs. LPLD 38.7°C, P = 0.43), or the median number of lesions per patient with temperature rise above 39°C (HPSD 1.5 vs. LPLD 2, P = 0.93). Radiofrequency ablation time (23.8 vs. 29.7 min, P < 0.01), PVI duration (46.5 vs. 59 min, P = 0.01), and procedure duration (133 vs. 150 min, P = 0.05) were reduced in HPSD. After a median follow-up of 12 months, AF recurrence was lower in HPSD (15.9% vs. LPLD 34.1%; hazard ratio 0.42, log-rank P = 0.04). CONCLUSION: Higher power short duration ablation was associated with similarly low rates of ETI and shorter total/PVI RF ablation times when compared with LPLD ablation. Higher power short duration ablation is a safe and efficacious approach to PVI.

Sudden cardiac death in congenital heart disease.

Sudden cardiac death (SCD) accounts for up to 25% of deaths in patients with congenital heart disease (CHD). To date, research has largely been driven by observational studies and real-world experience. Drawbacks include varying definitions, incomplete taxonomy that considers SCD as a unitary diagnosis as opposed to a terminal event with diverse causes, inconsistent outcome ascertainment, and limited data granularity. Notwithstanding these constraints, identified higher-risk substrates include tetralogy of Fallot, transposition of the great arteries, cyanotic heart disease, Ebstein anomaly, and Fontan circulation. Without autopsies, it is often impossible to distinguish SCD from non-cardiac sudden deaths. Asystole and pulseless electrical activity account for a high proportion of SCDs, particularly in patients with heart failure. High-quality cardiopulmonary resuscitation is essential to improve outcomes. Pulmonary hypertension and CHD complexity are associated with lower likelihood of successful resuscitation. Risk stratification for primary prevention implantable cardioverter-defibrillators (ICDs) should consider the probability of SCD due to a shockable rhythm, competing causes of mortality, complications of ICD therapy, and associated costs. Risk scores to better estimate probabilities of SCD and CHD-specific guidelines and consensus-based recommendations have been proposed. The subcutaneous ICD has emerged as an attractive alternative to transvenous systems in those with vascular access limitations, prior device infections, intra-cardiac shunts, or a Fontan circulation. Further improving SCD-related outcomes will require a multidimensional approach to research that addresses disease processes and triggers, taxonomy to better reflect underlying pathophysiology, high-risk features, early warning signs, access to high-quality cardiopulmonary resuscitation and specialized care, and preventive therapies tailored to underlying mechanisms.

Pacing-associated cardiomyopathy in adult congenital heart disease.

OBJECTIVES: Long-term single-site ventricular pacing may adversely affect ventricular function, due to dyssynchronous systemic ventricular contraction. We sought to determine the incidence, predictors and outcomes of pacing-associated cardiomyopathy (PACM) in an adult congenital heart disease (ACHD) cohort. METHODS: We retrospectively identified all patients in our database with a permanent pacemaker from 2000 to 2019. Patients were followed for the primary endpoint of unexplained decline in systemic ventricular function (PACM) and the secondary endpoint of heart failure admission. RESULTS: Of 2073 patients in our database, 106 had undergone pacemaker implantation. Over a median follow-up of 9.4 years, 25 patients (24%) developed PACM, but only in those with ventricular pacing percentage (VP%) ≥70%; PACM occurred in 0% of those with VP <70% and 47% of those with VP ≥70% (p<0.001). High-burden ventricular pacing (≥70%) remained predictive of PACM in transposition of the great arteries, tetralogy of Fallot and complex biventricular repair subgroups, but not in Fontan patients. Those with PACM were more likely to be admitted with heart failure (44% vs 15%, p=0.002). Cardiac resynchronisation therapy (CRT) upgrade was performed in 11 patients, with 9 responders (82%). CONCLUSIONS: In a cohort of patients with ACHD followed long-term post-pacing, 24% developed cardiomyopathy that was significantly associated with a higher burden of ventricular pacing (VP ≥70%). Given promising response rates to CRT, patients with ACHD expected to pace in the ventricle should be closely monitored for systemic ventricular decline.

Defibrillators in adult congenital heart disease: Long-term risk of appropriate shocks, inappropriate shocks, and complications.

AIMS: Sudden cardiac death (SCD) accounts for up to 25% of deaths in the adult congenital heart disease (ACHD) population. Current guidelines for defibrillator implantation are either extrapolated from acquired cardiac disease or are based upon single lesion studies, predominantly Tetralogy of Fallot (TOF). Defibrillator-related morbidity appears to be substantially higher in ACHD patients. METHODS: We retrospectively evaluated all patients in our ACHD database who received an implantable cardioverter-defibrillator (ICD) between 2000 and 2019, and who were ≥16 years old at time of implant. Patients were followed for appropriate shocks, inappropriate shocks, and complications. RESULTS: Of 4748 patients in our database, 59 patients (1.2%) underwent ICD implantation. ICDs were for primary prevention in 63% and secondary prevention in 37%. Over a median follow-up of 6.6 years, 24% received an appropriate shock, 27% an inappropriate shock, and 42% suffered a device-related complication (annualized risks of 3.2%, 3.6%, and 5.7%, respectively). There were no significant predictors of appropriate shocks or inappropriate shocks. All appropriate shocks in primary prevention patients occurred in TOF or transposition of the great arteries (TGA) with atrial switch, typically in the presence of multiple SCD risk factors. The majority of inappropriate shocks were due to supraventricular arrhythmias. Device-related mortality was 1.7% (0.3% per annum). CONCLUSIONS: Appropriate shocks were relatively common in an ACHD ICD population followed in the long term. Device-related morbidity was significant. Although risk factors have been established for TOF, and to a lesser extent TGA, risk stratification for ICD implantation in ACHD remains challenging.

Rugby Player's Aorta: Alarming Prevalence of Ascending Aortic Dilatation and Effacement in Elite Rugby Players.

BACKGROUND: Prompted by a cluster of observations concerning ascending aortic pathology in elite rugby players, we assessed over 150 asymptomatic predominantly retired players with echocardiography, aiming to document the prevalence and severity of ascending aortic dilatation and/or anterior aortic effacement, both 'risk factors' for potentially catastrophic aortic complications. METHODS: Rugby players (at least 5 years of high level competitive rugby) were classified as elite (national, state or first grade representatives) or non-elite. A total of 152 asymptomatic players with a mean age of 45 ± 13 years (range 21-65) underwent transthoracic echocardiography. Z-scores (number of standard deviations from a population mean) were calculated for aortic root and ascending aortic size. RESULTS: Regarding the aortic root, a Z-score of >2 was seen in 24% (expected prevalence 2.3%, p < 0.001) and a Z-score >3 was seen in 4% (expected prevalence 0..1%, p < 0.001). Sixty-two (62) players (41%) had an aortic root greater than 40 mm diameter. Ascending aortic Z-scores were >2 in 53% of players and >3 in 22% (p < 0.001). Abnormal anterior aortic effacement at the sinotubular junction (STJ) was seen in 88 players (58%). Abnormal aortic dilatation and effacement were associated with a longer duration of competitive rugby participation and elite status, respectively. CONCLUSIONS: Ascending aortic dilatation with abnormal anterior effacement is exceedingly common in asymptomatic retired elite rugby players. This warrants increased surveillance in retired players until the clinical significance of these findings can be further investigated.

Efficacy and adverse effects of sotalol in adults with congenital heart disease.

INTRODUCTION: Adults with congenital heart disease (CHD) are predisposed to arrhythmias, which can often be refractory to medical therapy. Sotalol is an attractive alternative antiarrhythmic to amiodarone in this younger patient population, given the latter's toxicity profile, but it may have proarrhythmic effects. We therefore aimed to assess the efficacy and safety of sotalol in adults with CHD. METHODS: We retrospectively assessed our adult CHD database for all patients ≥16 years old, with moderate to highly complex defects, who were prescribed sotalol between 2000 and 2017. Efficacy in treating the clinical arrhythmia was assessed as complete, partial or failure. Adverse effects, including proarrhythmia, were documented. RESULTS: Sotalol was prescribed in 82 of 902 adult CHD patients reviewed (9%). The mean age at sotalol commencement was 31.8 ±â€¯13.1 years, with a median time on sotalol of 2.8 years. The average prescribed dose was 122 ±â€¯51 mg/daily. Sotalol was completely effective in 48% (n = 39), partially effective in 46% (n = 38) and failed to control the clinical arrhythmia in 6% (n = 5). Fifteen patients (18%) discontinued sotalol due to a side effect, most commonly fatigue or dyspnoea. No episodes of torsades de pointes or sudden cardiac death were observed. Significant bradycardia related to sotalol occurred in 13% (n = 11, with permanent pacing implemented in 4), and was associated with Fontan anatomy. CONCLUSIONS: In moderate to highly complex adult CHD, sotalol was reasonably effective and safe in low doses. Side effects limiting treatment were typically non-life-threatening, with significant bradycardia related to sotalol more likely in Fontan patients.

Ablation of Atrial Arrhythmias After the Atriopulmonary Fontan Procedure: Mechanisms of Arrhythmia and Outcomes.

OBJECTIVES: This study sought to describe atrial arrhythmia mechanisms, acute outcomes, and long-term arrhythmia burdens following catheter ablation in adult atriopulmonary (AP) Fontan patients. BACKGROUND: Atrial arrhythmias are a significant cause of morbidity and mortality in the AP Fontan population. METHODS: Sixty consecutive atrial arrhythmia ablations were reviewed in 42 AP Fontan patients (31 ± 8 years of age), performed between 1998 and 2017. The number of induced and ablated tachycardias was recorded for each case, as well as the ability to ablate the suspected clinical tachycardia. Longer-term arrhythmia burden was assessed by using a 12-point clinical arrhythmia severity score. RESULTS: Intra-atrial re-entrant tachycardia (IART) was induced in 93% of cases (n = 56), atrioventricular re-entrant tachycardia in 2 (3%) and atrioventricular nodal re-entrant tachycardia in a single case. The mean number of tachycardias induced per case was 2.3. The critical isthmus for IART was mapped to the lateral (n = 10), inferolateral (n = 8), posterior/posterolateral (n = 16), or septal (n = 10) systemic venous atrium, or to the pulmonary venous atrium (n = 4). Ablation of all inducible tachycardias was achieved in 62%, ablation of at least one (but not all) inducible tachycardias in 25%, with failure to ablate any tachycardias in 13%. The suspected clinical arrhythmia was ablated in 50 cases (83%). Catheter ablation resulted in a significant reduction in arrhythmia score at 3 to 6, 12, and 24 months, irrespective of whether all inducible tachycardias were ablated, or the suspected clinical arrhythmia only. Twelve patients (29%) underwent at least one repeat ablation procedure, with a mean time between ablations of 2.7 ± 3.0 years. There were no cases of periprocedural death, stroke or cardiac tamponade. CONCLUSIONS: Catheter ablation can be a safe and effective intervention that will significantly reduce arrhythmia burden in the AP Fontan patient.

Adverse effects of amiodarone therapy in adults with congenital heart disease.

OBJECTIVE: Amiodarone is a highly effective antiarrhythmic therapy, however its toxicity profile often limits treatment. This is particularly relevant in adults with congenital heart disease (CHD), who are often young and in whom other antiarrhythmic agents commonly fail or are contraindicated. We sought to determine incidence and predictors of adverse effects caused by amiodarone in adult CHD (ACHD). DESIGN: A retrospective review of patients with moderate to complex ACHD treated with amiodarone at our center between 2000 and 2017 was performed. Incidence and predictors of adverse effects were described. Efficacy of amiodarone therapy in controlling the clinical arrhythmia was assessed as complete, partial, or failed. RESULTS: Amiodarone was prescribed in 57 patients of 902 ACHD patients reviewed (6%), for a mean duration of 2.7 ± 4.3 years. Significant adverse effects occurred in 56%, most commonly thyroid dysfunction, with amiodarone-induced thyrotoxicosis (AIT) in 30% and amiodarone-induced hypothyroidism in 14%. AIT frequently led to arrhythmia exacerbation and occurred most in those with Fontan anatomy. Severe dermatological effects were seen in 7% and bradycardia requiring pacing in 5%. Interstitial lung disease, peripheral neuropathy and alopecia were observed in single cases. Amiodarone toxicity led to discontinuation of the drug in 42%. Amiodarone was highly effective when tolerated, however, achieving complete arrhythmia control in 63%, partial control in 35%, with failure to control in only one patient. CONCLUSIONS: Amiodarone therapy is effective in moderate to complex ACHD patients, but is frequently limited by adverse effects. ACHD patients seem especially vulnerable to thyroid dysfunction, with Fontan patients in particular at increased risk of AIT.

Causes of death in a contemporary adult congenital heart disease cohort.

OBJECTIVE: The life expectancy of patients with congenital heart disease (CHD) has significantly improved with advances in their paediatric medical care. Mortality patterns are changing as a result. Our study aims to describe survival and causes of death in a contemporary cohort of adult patients with CHD. METHODS: We reviewed 3068 patients in our adult CHD database (age ≥16 years, seen at least once in our centre between 2000 and 2015), and documented the number and causes of death, via Australia's National Death Index. Survival and mortality patterns were analysed by complexity of CHD and by underlying congenital diagnosis. RESULTS: Our cohort comprised 3068 adult patients (53% male). The distribution of patients (per the Bethesda classification) was 47% simple, 34% moderate and 18% complex (1% not classifiable). Over a median follow-up of 6.2 years (IQR 3.5-10.4), 341 patients (11%) died with an incidence of 0.4 deaths/100 patient years (py). Survival was significantly worse with increasing complexity of CHD (p<0.001); mortality rate in the simple group was 0.3 deaths/100 py with a median age of death 70 years, and in the complex group was 1.0 death/100 py with a median age of death 34 years. Overall, non-cardiac causes of death outnumbered cardiac causes, at 54% and 46%, respectively. The leading single cause of death was heart failure (17%), followed by malignancy (13%). Simple adult CHD patients mostly died due to non-cardiac causes such as malignancy. Perioperative mortality only accounted for 5% of deaths. CONCLUSIONS: Premature death is common in adults with CHD. Although heart failure remains the most common cause of death, in the contemporary era in a specialist CHD centre, non-cardiac related deaths outnumber cardiac deaths, particularly in those with simple CHD lesions.

Impact of Perturbed Pancreatic ß-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism.

Elevated pancreatic ß-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased ß-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in ß-cells (ß-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The ß-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of ß-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify ß-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes.

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy.

OBJECTIVE: • To examine whether nerve-sparing surgery (NSS) is a risk factor for positive surgical margins (PSMs) in patients with either organ-confined prostate cancer or extracapsular extension (ECE). PATIENTS AND METHODS: • Clinicopathological outcome data on 945 consecutive patients treated with radical prostatectomy (RP) were prospectively collected. • All patients underwent RP (bilateral, unilateral or non-NSS) by one surgeon between 2002 and 2007. • Risk of PSMs and their locations with respect to NSS was determined by multivariate logistic regression analysis adjusting for preoperative risk factors for PSMs within pT2, pT3a and pT3b tumours. RESULTS: • Overall a PSM was identified in 19.6% of patients in an unscreened population with mean prostate-specific antigen (PSA) level of 8.1 ng/mL. • There was no significant difference in rates of PSMs between NSS groups on multivariate analysis (P= 0.147). • There was no significant difference in pT2 (P= 0.880), pT3a (P= 0.175) or pT3b (P= 0.354) tumours. • The only significant predictor of PSMs was preoperative PSA level (risk ratio 1.289, P= 0.006). • There was no significant difference in the location of PSMs except for the pT3a group, where the patients that had bilateral NSS were at higher risk of a posterolateral PSM (P= 0.028). CONCLUSIONS: • With appropriate selection of patients, NSS does not increase the risk of PSMs, whether the cancer is organ confined or ECE is present. • The adverse impact of the NSS procedure in the hands of an experienced surgeon is minimal and is a realistic compromise to obtain the increase in health-related quality of life offered by NSS.