Subcutaneous Implantable Cardioverter-Defibrillators in Patients With Congenital Heart Disease.

BACKGROUND: Very few data have been published on the use of subcutaneous implantable cardioverter-defibrillators (S-ICDs) in patients with congenital heart disease (CHD). OBJECTIVES: The aim of this study was to analyze outcomes associated with S-ICDs in patients with CHD. METHODS: This nationwide French cohort including all patients with an S-ICD was initiated in 2020 by the French Institute of Health and Medical Research. Characteristics at implantation and outcomes were analyzed in patients with CHD. RESULTS: From October 12, 2012, to December 31, 2019, among 4,924 patients receiving an S-ICD implant in 150 centers, 101 (2.1%) had CHD. Tetralogy of Fallot, univentricular heart, and dextro-transposition of the great arteries represented almost one-half of the population. Patients with CHD were significantly younger (age 37.1 ± 15.4 years vs 50.1 ± 14.9 years; P < 0.001), more frequently female (37.6% vs 23.0%; P < 0.001), more likely to receive an S-ICD for secondary prevention (72.3% vs 35.9%; P < 0.001), and less likely to have severe systolic dysfunction of the systemic ventricle (28.1% vs 53.1%; P < 0.001). Over a mean follow-up period of 1.9 years, 16 (15.8%) patients with CHD received at least 1 appropriate shock, with all shocks successfully terminating the ventricular arrhythmia. The crude risk of appropriate S-ICD shock was twice as high in patients with CHD compared with non-CHD patients (annual incidences of 9.0% vs 4.4%; HR: 2.1; 95% CI: 1.3-3.4); however, this association was no longer significant after propensity matching (especially considering S-ICD indication, P = 0.12). The burden of all complications (HR: 1.2; 95% CI: 0.7-2.1; P = 0.4) and inappropriate shocks (HR: 0.9; 95% CI: 0.4-2.0; P = 0.9) was comparable in both groups. CONCLUSIONS: In this nationwide study, patients with CHD represented 2% of all S-ICD implantations. Our findings emphasize the effectiveness and safety of S-ICD in this particularly high-risk population. (S-ICD French Cohort Study [HONEST]; NCT05302115).

Incidence and predictors of pacemaker implantation at follow-up after reversible high-degree sinus node dysfunction or atrioventricular block.

BACKGROUND: A pacemaker implantation is not indicated in cases of reversible high-degree symptomatic sinus node dysfunction (SND) and atrioventricular block (AVB). However, it remains uncertain whether these reversible automaticity/conduction disorders may recur in some patients at follow-up, in the absence of reversible cause. This retrospective study aimed to determine the incidence and predictive factors of permanent pacemaker (PPM) implantation at follow-up and after reversible high-degree SND/AVB. METHODS: Based on medical electronic files codes, we identified patients who were hospitalized in our cardiac intensive care unit between January 2003 and December 2020 due to reversible high-degree SND/AVB and who were discharged from the hospital alive and without PPM implantation. Acute myocardial infarction and post-cardiac surgery patients were excluded. We categorized the patients according to the need for PPM at follow-up due to non-reversible high-degree SND/AVB. RESULTS: Of the 93 patients included, 26 patients (28%) were readmitted for PPM implantation at follow-up after hospital discharge. Among baseline characteristics, compared with patients who did not have high-degree SND/AVB recurrence, those who had subsequent PPM implantation had less frequent previous hypertension (70% vs. 46%, p = .031). Regarding the initial causes of reversible SND/AVB, isolated hyperkalemia was found more often in the patients readmitted for PPM (19% vs. 3% vs. p = .017). Moreover, recurrence of high-degree SND/AVB was significantly associated with the presence of intraventricular conduction disorders (either bundle branch block or left bundle branch hemiblock) on ECG at discharge (36% in patients without PPM vs. 68% in PPM patients, p = .012). CONCLUSION: Almost one third of the patients discharged alive from the hospital after a reversible high-degree SND/AVB needed a pacemaker implantation at follow-up. Complete bundle branch block or left bundle branch hemiblock on discharge ECG after recovery of atrioventricular conduction and/or sinus automaticity was associated with a greater risk of recurrence leading to pacemaker implantation.

Supraventricular tachycardias, conduction disease, and cardiomyopathy in 3 families with the same rare variant in TNNI3K (p.Glu768Lys).

BACKGROUND: Rare genetic variants in TNNI3K encoding troponin-I interacting kinase have been linked to a distinct syndrome consisting primarily of supraventricular tachycardias and variably expressed conduction disturbance and dilated cardiomyopathy in 2 families. OBJECTIVE: The purpose of this study was to identify new genetic variants associated with inherited supraventricular tachycardias, cardiac conduction disease, and cardiomyopathy. METHODS: We conducted next generation sequencing in 3 independent multigenerational families with atrial/junctional tachycardia with or without conduction disturbance, dilated cardiomyopathy, and sudden death. We also assessed the effect of identified variant on protein autophosphorylation. RESULTS: In this study, we uncovered the same ultra-rare genetic variant in TNNI3K (c.2302G>A, p.Glu768Lys), which co-segregated with disease features in all affected individuals (n = 23) from all 3 families. TNNI3K harboring the TNNI3K-p.Glu768Lys variant displayed enhanced kinase activity, in line with expectations from previous mouse studies that demonstrated increased conduction indices and procardiomyopathic effects with increased levels of Tnni3k. CONCLUSION: This study corroborates further the causal link between rare genetic variation in TNNI3K and this distinct complex phenotype, and points to enhanced kinase activity of TNNI3K as the underlying pathobiological mechanism.

Impact of clinical and genetic findings on the management of young patients with Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) that seldom manifests or is recognized in childhood. OBJECTIVES: The objectives of this study were to describe the clinical presentation of pediatric BrS to identify prognostic factors for risk stratification and to propose a data-based approach management. METHODS: We studied 106 patients younger than 19 years at diagnosis of BrS enrolled from 16 European hospitals. RESULTS: At diagnosis, BrS was spontaneous (n = 36, 34%) or drug-induced (n = 70, 66%). The mean age was 11.1 ± 5.7 years, and most patients were asymptomatic (family screening, (n = 67, 63%; incidental, n = 13, 12%), while 15 (14%) experienced syncope, 6(6%) aborted SCD or symptomatic ventricular tachycardia, and 5 (5%) other symptoms. During follow-up (median 54 months), 10 (9%) patients had life-threatening arrhythmias (LTA), including 3 (3%) deaths. Six (6%) experienced syncope and 4 (4%) supraventricular tachycardia. Fever triggered 27% of LTA events. An implantable cardioverter-defibrillator was implanted in 22 (21%), with major adverse events in 41%. Of the 11 (10%) patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 (71%) patients, and SCN5A rare variants were identified in 58 (55%); 15 of 32 tested probands (47%) were genotype positive. Nine of 10 patients with LTA underwent genetic testing, and all were genotype positive, whereas the 17 SCN5A-negative patients remained asymptomatic. Spontaneous Brugada type 1 electrocardiographic (ECG) pattern (P = .005) and symptoms at diagnosis (P = .001) were predictors of LTA. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous Brugada type 1 ECG pattern (P = .006). CONCLUSION: Spontaneous Brugada type 1 ECG pattern and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific, and prevention of SCD may involve genetic testing and aggressive use of antipyretics and quinidine, with risk-specific consideration for the implantable cardioverter-defibrillator.

Usefulness and limitations of contractile reserve evaluation in patients with low-flow, low-gradient aortic stenosis eligible for cardiac resynchronization therapy.

AIMS: In low-flow, low-gradient aortic stenosis (LF/LG AS), the assessment of contractile reserve (CR) by dobutamine stress echocardiography (DSE) is recommended for risk stratification and treatment strategy. However, DSE may show limitations in cases of left ventricular dyssynchrony (LVD). The impact of LVD in LF/LG AS, and the feasibility of CRT in this setting have never been evaluated. We aimed to assess: (i) the proportion of LF/LG AS patients with LVD; (ii) the influence of LVD on CR at DSE; and (iii) the effects of CRT in these patients. METHODS AND RESULTS: Thirty consecutive patients with LF/LG AS underwent DSE with study of CR. The operative risk for aortic valve replacement (AVR) was assessed using the logistic EuroSCORE. Twenty-one of the 30 patients had LVD. They were significantly older, more symptomatic, had a higher EuroSCORE, and a lower prevalence of CR than those with a narrow QRS (47% vs. 100%, P = 0.009). A CRT pacemaker was implanted in 19 of the 21 patients with LVD. All 19 (except for one patient who died suddenly) experienced significant clinical and echocardiographic improvement. Fourteen CRT patients underwent subsequent AVR with a low event rate. Four CRT patients refused AVR; two of them worsened again 1-2 years post-CRT. CONCLUSION: LVD is common in LF/LG AS patients and may be a major mechanism of afterload mismatch, as well as a cause of underdetection of CR. CRT in this population is feasible and may be proposed as a bridge to surgery.

Permanent left atrial pacing therapy may improve symptoms in heart failure patients with preserved ejection fraction and atrial dyssynchrony: a pilot study prior to a national clinical research programme.

AIMS: Our group has recently shown that in some patients, heart failure with preserved ejection fraction (HFPEF) may be explained by 'atrial dyssynchrony syndrome' (ADS) due to interatrial conduction delay (IACD), a short left atrioventricular interval (LAVI), and increased left atrial (LA) stiffness. Our primary objective was to evaluate LA pacing therapy as a new treatment to restore left ventricular active filling in patients with no other known causes for HF than ADS. METHODS AND RESULTS: Six patients with severe HFPEF with IACD (P wave duration >120 ms in lead II), short LAVI during electrophysiological studies (<70 ms), a restrictive filling pattern (E/e' >15), and no standard indication for a pacemaker were implanted with a lead screwed inside the coronary sinus for active LA pacing. After 3 months of active pacing, a 2 week randomized double-blind crossover phase compared active vs. inactive LA pacing. After 3 months of pacing, the mean distance walked in 6 min (6MWD) was 21% greater (240 ± 25 m vs. 190 ± 15m, P < 0.05), mitral A wave duration was longer (104 ± 8 vs. 158 ± 25 ms, P = 0.002), and E/A and E/e' ratios were smaller (3.4 ± 1.3 vs. 1.8 ± 0.9, P = 0.009, and 22.6 ± 4.6 vs. 15.3 ± 4.3, P = 0.006, respectively). Inactivation of pacing for 1 week led to a significant reduction in the 6MWD, with an on/off response. CONCLUSION: The beneficial effects of LA pacing observed in this pilot study will have to be confirmed by the randomized, controlled crossover 'LEAD' study.

Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy.

OBJECTIVES: The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. BACKGROUND: Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias. METHODS: Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified. RESULTS: Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine. CONCLUSIONS: A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine.

Atrial dyssynchrony syndrome: an overlooked phenomenon and a potential cause of 'diastolic' heart failure.

AIMS: The purpose of the present study was too explore the role of interatrial dyssynchrony in heart failure with preserved ejection fraction (HFPEF). METHODS AND RESULTS: For the case study we selected seven patients with severe HFPEF, with interatrial block on electrocardiogram (ECG), and a delayed and interrupted A wave on mitral Doppler. Echocardiographic left atrial (LA) volumes/functions, mitral E/A and E/e' ratios, mitral A wave duration/deceleration time, and interatrial mechanical delays (IAMDs) at tissue Doppler, were studied. We performed right heart catheterization, and an electrophysiological study (EPS) for the measurement of interatrial conduction delay (IACD) and left atrioventricular interval (LAVI). Mean IAMD was 106 ms. All the patients exhibited a restrictive mitral Doppler pattern, high E/A and E/e' ratios, and short A wave duration/deceleration time. Left atrial volume was increased, with severely depressed functions. Right heart catheterization showed severe post-capillary pulmonary hypertension. The EPS showed an IACD of 170 ± 20 ms, with a short LAVI. Left atrial pacing through the coronary sinus reduced the IACD to 25 ± 15 ms. In the pilot study, 29 patients with HFPEF were compared with 27 age-matched control patients. HFPEF patients had longer P waves, shorter A waves, and a longer IAMD than the controls. Prevalence of severe IAMD >60 ms was 59% in HFPEF and 0% in controls. In the HFPEF group, patients with an IAMD >60 ms had significantly shorter A waves and higher E/e' ratio. CONCLUSION: Some HFPEF patients present with IACD, delayed LA systole, shortened LA emptying, decreased LA compliance, and increased filling pressures. Whether the condition of these patients could be improved by atrial resynchronization deserves further investigation.

Sporadic arrhythmogenic right ventricular cardiomyopathy/dysplasia due to a de novo mutation.

We report the case of a 41-year-old man with a diagnosis of sporadic arrhythmogenic right ventricular cardiomyopathy (ARVC). Genetic screening identified the heterozygous missense mutation R49H in the desmoglein-2 gene. The mutation was absent in both parents, and we demonstrated that it was a de novo mutation. To the best of our knowledge, this is the first description of a de novo mutation in ARVC. This has important implications, including for clinical practice, since individuals with sporadic ARVC caused by a de novo mutation can transmit the disease gene to 50% of their offspring. This suggests that the benefit of molecular genetics can be extended to sporadic ARVC and may improve genetic counselling.

Anotomic interaction between the aortic root and the atrial septum: a prospective echocardiographic study.

BACKGROUND: We recently demonstrated that patients with platypnea-orthodeoxia syndrome and an enlarged aortic root had a smaller and hypermobile atrial septum (AS) compared with those with a normal aortic root. However, this was a partly retrospective study. METHODS: In all, 72 patients underwent transesophageal echocardiography and cardiac catheterization. The aortic root diameter, AS dimension, AS oscillation amplitude (ASo), and atrial pressure gradient were measured. RESULTS: Significant correlations were found: aortic root diameter and AS dimension (r = -0.5, P < .001), aortic root diameter and ASo (r = +0.3, P = .014), AS dimension and ASo (r = -0.28, P = .02), and ASo and atrial pressure gradient (r = -0.36, P = .003). Nineteen patients presented with patent foramen ovale; those with grade 3 shunting had significantly higher mobility of the AS and larger aortic roots. CONCLUSION: These results confirm that an increasing aortic size affects the AS by decreasing its apparent size and increasing its mobility. In case of a patent foramen ovale, increased AS mobility is associated with greater shunting.

A randomized clinical trial of continuous flow nitrous oxide and nalbuphine infusion for sedation of patients during radiofrequency atrial flutter ablation.

BACKGROUND: In patients with common atrial flutter (CAF), radiofrequency ablation (RFA) causes discomfort. Patients undergoing RFA often feel pain which is difficult to control as the mechanisms are unclear. HYPOTHESIS: Inhaled nitrous oxide (N2O) is a potent sedative-analgesic-anxiolytic agent that may relieve anxiety and discomfort during CAF ablation. METHODS AND RESULTS: In a prospective randomized study, the effect of Inhaled N2O was compared with that of intravenous sedation with Nalbuphine during CAF ablation in 76 patients (64 +/- 13 years, 56 men). We used a 24 pole mapping catheter around the tricuspid annulus and a 8-mm tip ablation catheter for each patient. Forty-two patients (group 1) underwent radiofrequency (RF) application to the cavotricuspid isthmus 5 minutes after the beginning of inhalation of a (50% N2O/50% O2) mixture. Thirty-four patients (group 2), underwent the first RF application 15 minutes after the end of an infusion of Nalbuphine (20 mg delivered over 15 minutes). Ablation-related anxiety and discomfort were assessed using a visual analog scale (VAS) ranging from 0 to 100 mm, with 0 correlating to the statement "no pain at all" and 100 with "the worst possible pain." The VAS score was determined at the end of each application. The number of RF applications (group 1; 10 +/- 8 vs group 2; 11 +/- 6, P = NS) and procedure duration (group 1; 75 +/- 53 minutes vs group 2; 72 +/- 45 minutes, P = NS), were similar for the two groups. N(2)O sedation compared with nalbuphine infusion reduced VAS for anxiety (10 mm +/- 8 vs 58 mm +/- 22, P < 0.05) and for discomfort (18 mm +/- 9 vs 45 mm +/- 34, P < 0.01), respectively. Although there was more frequent vomiting in group 1; 7 of 42 (17%) than in group 2; 3 of 34 (9%), P < 0.05, patients were less likely to have hypotension during the procedure 1 of 42 (2.5%) versus 4 of 34 (12%), P < 0.05, respectively. CONCLUSION: Inhalation of a (50% N2O/50% O2) mixture during RF ablation for atrial flutter is a safe and efficient way to reduce anxiety and discomfort caused by RF applications.

Simple and efficient identification of conduction gaps in post-ablation recurring atrial flutters.

AIMS: Cavo-tricuspid isthmus (CTI) radiofrequency (RF) ablation is a curative therapy for common atrial flutter (AFl), but is associated with a recurrence rate of 5-26%. Although complete bidirectional conduction block is usually achieved, the recurrence of AF is due to recovered conducting isthmus tissue through which activation wavefronts pass. We evaluated a simple and efficient electrophysiological strategy, which pinpoints the ablation target. METHODS AND RESULTS: Twenty-five patients (19 men), mean age 61 +/- 6, with recurrent AFl required a repeat ablation, 250 +/- 160 days after a successful RF CTI procedure. Transverse CTI conduction was monitored during AFl or coronary sinus (CS) pacing by a 24-pole mapping catheter positioned in the right atrium (RA), with the distal poles in the CS, proximal poles on the lateral RA, and intermediate poles on the CTI. A slow conduction area traversing the CTI (velocity, 37 +/- 22 vs. 98 +/- 26 cm/s on either side, P < 0.05) and a lower potential amplitude than at both sides (0.2 +/- 0.15 vs. 0.5 +/- 0.5 mV, P < 0.05), defined by a bayonet-shaped depolarization sequence, were considered to represent the incomplete line of block (InLOB). An ablation catheter was progressively dragged up to this InLOB, from the tricuspid annulus to the inferior vena cava, analysing the widely separated double potentials (DPs) until these coalesced. In nine patients (35%), the target conduction gap was a coalesced fractionated atrial potential within the InLOB (duration, 77 +/- 12 ms), and in 16 patients (65%), a narrow DP toward the healthy margins of this InLOB (duration, 28 +/- 15 ms). Adopting this strategy yields 100% successful re-ablation of recurring AFl leading to bidirectional block, with a mean 2.7 +/- 1.4 RF applications. CONCLUSION: Transverse CTI mapping precisely locates the InLOB and helps find conduction gaps along the CTI in re-ablation procedures for common AFl.

A new and simple method for distinguishing complete from incomplete block through the cavotricuspid isthmus.

BACKGROUND: A complete line of block (CLOB) in the cavotricuspid isthmus (CTI) is the endpoint of typical atrial flutter ablation. Before CTI block is obtained, a progressive CTI conduction delay due to an incomplete line of block (InLOB) can be difficult to distinguish from CLOB. The purpose of this study was to assess a new simple approach based on the changes in atrio-ventricular (AV) conduction delays during septal and lateral right atrial pacing, to distinguish a CLOB from an InLOB during typical atrial flutter (AFL) ablation. METHODS AND RESULTS: Forty patients who presented an InLOB before a CLOB, and a stable (AV) conduction delay at 600 ms cycle length pacing (when in sinus rhythm), during AFL ablation were included in this study. A 24-pole mapping catheter was positioned so that 2 adjacent dipoles bracketed the targeted CTI line of block (LOB), with proximal dipoles lateral to the LOB and distal dipoles in the coronary sinus. Two pacing sites were lateral (position L1 and L2) and one was septal (position S) to the LOB, with locations L1 and S closest to the LOB. During L1, L2 and S site pacing, the delay between the pacing artefact and the peak of the R wave in a surface ECG (lead II) was measured. We measured the following conduction delays (mean +/- SD in ms), during InLOB versus CLOB: (L1 to R) 320.5 +/- 68.0 versus 367.0 +/- 62.0, p = 0.001; (L2 to R) 333.0 +/- 59.0 versus 338.0 +/- 62.0, p = 0.663, (S to R) 259.4 +/- 51.5 versus 247.1 +/- 55.5, p = 0.987. We calculated the following data during an InLOB versus a CLOB: (L1R-L2R) -12.3 +/- 7 versus 20.2 +/- 12.7, p = 0.001; (L1R-SR) 51.1 +/- 21.5 versus 120.1 +/- 16.6, p < 0.05. The sensitivity, specificity, positive and negative predictive values for CLOB with (L1R-SR > 94 ms) and with (L1R-L2R > 0 ms) were respectively; 100%, 98%, 98% and 100%. CONCLUSIONS: This study establishes that lateral versus septal right atrial pacing sites combined with the measure of AV conduction delay on a surface ECG can be useful to distinguish a CLOB from an InLOB during AFL ablation.