Khairy, Paul

Abstract Background and Aims There is a paucity of data on arrhythmia burden in patients with congenitally corrected transposition of the great arteries (ccTGAs). The present study sought to quantify the incidence of atrial arrhythmia (AA), ventricular arrhythmia (VA), and complete atrioventricular block (CAVB) in patients with ccTGA and identify associated factors. Methods An international, multi-centre, retrospective cohort study was conducted in 29 tertiary hospitals (six countries) between 1990 and 2018. Primary analyses consisted of determining the incidence of a combined outcome consisting of AA, VA, or CAVB, along with its individual components. Factors associated with the different types of arrhythmias were assessed by uni-variable and multi-variable Cox regression analyses. Results A total of 1131 patients with ccTGA were followed for 9.0 (interquartile range 4.0–17.2) years. Cumulative rates of the primary endpoint at 10, 15, and 20 years were 44.5%, 51.0%, and 58.8%, respectively. AA, VA, and CAVB occurred in 2.1, 1.4, and 2.0 cases per 100 person-years, respectively. In multi-variable analyses, surgery/intervention conferred a greater than three-fold higher risk of AA [hazard ratio (HR) 3.01, 95% confidence interval (CI) 1.90–4.78, P < .001]. Furthermore, surgery/intervention was significantly associated with a greater risk of VA (HR 1.73, 95% CI 0.98–3.05, P = .003) and CAVB (HR 3.65, 95% CI 2.20–6.05, P < .001). The left bundle branch block was associated with a higher risk of VA (HR 4.03, 95% CI 1.59–10.23, P = .003) and the right bundle branch block with a higher risk of CAVB (HR 3.71, 95% CI 1.81–7.63, P < .001). Conclusions The arrhythmia burden in patients with ccTGA is substantial, with a high incidence of AA, VA, and CAVB.

Background The objective of this international multicenter study was to investigate both early and late outcomes of cardiac resynchronization therapy (CRT) in patients with a systemic right ventricle (SRV) and to identify predictors for congestive heart failure readmissions and mortality. Methods and Results This retrospective international multicenter study included 13 centers. The study population comprised 80 adult patients with SRV (48.9% women) with a mean age of 45±14 (range, 18–77) years at initiation of CRT. Median follow‐up time was 4.1 (25th–75th percentile, 1.3–8.3) years. Underlying congenital heart disease consisted of congenitally corrected transposition of the great arteries and dextro‐transposition of the great arteries in 63 (78.8%) and 17 (21.3%) patients, respectively. CRT resulted in significant improvement in functional class (before CRT: III, 25th–75th percentile, II–III; after CRT: II, 25th–75th percentile, II–III; P =0.005) and QRS duration (before CRT: 176±27; after CRT: 150±24 milliseconds; P =0.003) in patients with pre‐CRT ventricular pacing who underwent an upgrade to a CRT device (n=49). These improvements persisted during long‐term follow‐up with a marginal but significant increase in SRV function (before CRT; 30%, 25th–75th percentile, 25–35; after CRT: 31%, 25th–75th percentile, 21–38; P =0.049). In contrast, no beneficial change in the above‐mentioned variables was observed in patients who underwent de novo CRT (n=31). A quarter of all patients were readmitted for heart failure during follow‐up, and mortality at latest follow‐up was 21.3%. Conclusions This international experience with CRT in patients with an SRV demonstrated that CRT in selected patients with SRV dysfunction and pacing‐induced dyssynchrony yielded consistent improvement in QRS duration and New York Heart Association functional status, with a marginal increase in SRV function.

Background: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. Methods: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. Results: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. Conclusions: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Abstract Introduction Right ventricular (RV) size informs about prognosis and need for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). Cardiac magnetic resonance (CMR) is considered the reference standard for measurement of RV volumes. Despite known limitations for RV evaluation, 2D transthoracic echocardiography (TTE) remains the primary and most available imaging modality in the rTOF population. Purpose To determine which TTE RV size parameters best correlate with CMR-derived indexed RV end-diastolic (RVEDVi) and end-systolic (RVESVi) volumes in the rTOF population. We sought to determine the best TTE measurement thresholds to predict normal RV volume (RVEDVi ≤110 mL/m2) and significant RV dilatation by CMR (RVEDVi ≥150ml/m2). Method We retrospectively enrolled all rTOF patients followed at a single-center between 2010 and 2018 who had both TTE and CMR exams performed within a 12-month interval. All TTE exams were reviewed by an observer measuring RV areas, RV inlet and RV outlet at end-diastole and end-systole. Analyses of CMR studies were performed by 3 observers who measured RV area, RV inlet, RV outlet and RV volumes at end-diastole and end-systole. Correlations between TTE and CMR parameters were performed using Pearson correlation coefficients. Using the TTE RV parameters with the strongest correlation with CMR, we subsequently determined thresholds to predict a CMR RVEDVi ≤110ml/m2 and ≥150ml/m2 using ROC analysis. Results We enrolled 130 patients (59 women [45%], mean age 43±12.8 years). Median age at TOF repair was 4 [3–6] years; 18 patients (14%) had subsequent pulmonary valve replacement. Median interval between TTE and CMR exams was 114 [59–239] days. There were significant correlations between all TTE parameters and CMR RVEDVi. TTE indexed RV end-diastolic area (RVEDAi) most strongly correlated with CMR RVEDVi (r=0.73, p<0.0001). All TTE RV parameters significantly correlated with CMR RVESVi but indexed RV end-systolic area had the strongest correlation (r=0.77, p<0.0001). ROC analysis performed to predict RVEDVi of ≤110ml/m2 and ≥150ml/m2 using TTE RVEDAi revealed areas under the curve of 0.86±0.04 and 0.90±0.03, respectively. A TTE RVEDAi ≤17cm2/m2 predicted a normal CMR RV volume (≤110ml/m2) with a sensitivity of 90% and a specificity of 74%. A TTE RVEDAi ≥19cm2/m2 predicted a CMR RVEDVi ≥150 mL/m2 with a sensitivity of 93% and a specificity of 76%. Conclusion In rTOF patients, both diastolic and systolic TTE RV area best correlate with CMR-derived RV end-diastolic and end-systolic volumes. A cut-off value of TTE RVEDAi of 19cm2/m2 is 93% sensitive and 76% specific to predict a CMR RVEDVi ≥150ml/m2. Simple RV size measurement using TTE may help inform the need and frequency of CMR evaluations in rTOF patients.

Background— Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. Methods and Results— The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03–4.61; P =0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P <0.001). Among patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82–8.11; P <0.001) was associated with LR. Conversely, early reablation was associated with greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR, 0.04; 95% CI, 0.01–0.32; P =0.002). Conclusions— ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.