Long-Term Follow-Up of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator: The DAI-T4F Nationwide Registry.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. METHODS: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]). CONCLUSIONS: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574.

Cardiac resynchronization therapy plus coupled pacing improves acutely myocardial function in heart failure patients.

BACKGROUND: Coupled pacing (CP), which consists of an additional beat delivered after ventricular refractory period, has been proposed to reduce ventricular rate and increase ventricular contractility. We hypothesized that CP may be added to cardiac resynchronization therapy (CRT) to improve CRT effect in heart failure (HF) patients. METHODS: The study included 20 consecutive HF patients in sinus rhythm referred for CRT-defibrillator (CRT-D) implantation (baseline left ventricular ejection fraction [LVEF] 27 ± 6%, baseline QRS duration 149 ± 33 ms, age = 63 ± 11 years). CP associated with CRT (CRT + CP) was delivered during CRT-D implantation from the right and left ventricular leads simultaneously. Echocardiography data were collected at baseline, during CRT and CRT + CP to assess changes in LVEF, cardiac output (CO), longitudinal global strain assessed by speckle tracking, and LV dyssynchrony (opposing wall delay using tissue Doppler imaging). RESULTS: Compared to the conventional CRT, heart rate (HR) markedly decreased during CRT + CP (79 ± 20 beats/min vs 51 ± 8 beats/min, P < 0.0001) and was associated with a significant increase in LVEF (30 ± 8% vs 35 ± 8%, P = 0.0002) and peak of longitudinal global strain (-6 ± 2% vs -8 ± 2%, P < 0.0001). Importantly, during CRT + CP, CO increased (3.8 ± 1.0 L/min vs 4.4 ± 1.4 L/min, P = 0.004) and cardiac synchronicity remained unchanged (38 ± 24 ms for CRT alone vs 27 ± 18 ms for CRT + CP, P = 0.1). CONCLUSION: In sinus rhythm HF patients, acute CP application in addition to CRT decreases HR and contributes to myocardial contractility and CO improvement without deleterious impact on ventricular synchronicity.

Rapid ventricular tachycardia in patients with tetralogy of Fallot and implantable cardioverter-defibrillator: Insights from the DAI-T4F nationwide registry.

BACKGROUND: In repaired tetralogy of Fallot (TOF), little is known about characteristics of patients with rapid ventricular tachycardia (VT). Also, whether patients with a first episode of nonrapid VT may subsequently develop rapid VT or ventricular fibrillation (VF) has not been addressed. OBJECTIVES: The objectives of this study were to compare patients with rapid VT/VF with those with nonrapid VT and to assess the evolution of VT cycle lengths (VTCLs) overtime. METHODS: Data were analyzed from a nationwide registry including all patients with TOF and implantable cardioverter-defibrillator (ICD) since 2000. Patients with ≥1 VT episode with VTCL ≤250 ms (240 beats/min) formed the rapid VT/VF group. RESULTS: Of 144 patients (mean age 42.0 ± 12.7 years; 104 [72%] men), 61 (42%) had at least 1 VT/VF episode, including 28 patients with rapid VT/VF (46%), during a median follow-up of 6.3 years (interquartile range 2.2-10.3 years). Compared with patients in the nonrapid VT group, those in the rapid VT/VF group were significantly younger at ICD implantation (35.2 ± 12.6 years vs 41.5 ± 11.2 years; P = .04), had more frequently a history of cardiac arrest (8 [29%] vs 2 [6%]; P = .02), less frequently a history of atrial arrhythmia (11 [42%] vs 22 [69%]; P = .004), and higher right ventricular ejection fraction (43.3% ± 10.3% vs 36.6% ± 11.2%; P = .04). The median VTCL of VT/VF episodes was 325 ms (interquartile range 235-429 ms). None of the patients with a first documented nonrapid VT episode had rapid VT/VF during follow-up. CONCLUSION: Patients with TOF and rapid VT/VF had distinct clinical characteristics. The relatively low variation of VTCL over time suggests a room for catheter ablation without a backup ICD in selected patients with well-tolerated VT.

Electrical cardioversion of atrial arrhythmias with cardiac amyloidosis in the era of direct oral anticogulants.

AIMS: Atrial fibrillation (AF)/atrial flutter is common during cardiac amyloidosis (CA). Electrical cardioversion (EC) is a strategy to restore sinus rhythm (SR). However, left atrial thrombus (LAT) represents a contraindication for EC. CA patients with AF/atrial flutter have a high prevalence of LAT. We aimed to evaluate EC characteristics, LAT prevalence and risk factors, and AF/atrial flutter outcome in CA patients undergoing EC, predominantly treated with direct oral anticoagulants (DOACs). METHODS AND RESULTS: All patients with CA and AF/atrial flutter referred for the first time to our national referral centre of amyloidosis for EC from June 2017 to February 2021 were included in this study. In total, 66 patients (median age 74.5 [70;80.75] years, 67% male) were included with anticoagulation consisted of DOAC in 74% of cases. All patients underwent cardiac imaging before EC to rule out LAT. EC was cancelled due to LAT in 14% of cases. Complete thrombus resolution was observed in only 17% of cases. The two independent parameters associated with LAT were creatinine [hazard ratio (HR) = 1.01; confidence interval (CI) = 1.00-1.03, P = 0.036] and the use of antiplatelet agents (HR = 13.47; CI = 1.85-98.02). EC acute success rate was 88%, and we observed no complication after EC. With 64% of patients under amiodarone, AF/atrial flutter recurrence rate following EC was 51% after a mean follow-up of 30 ± 27 months. CONCLUSIONS: Left atrial thrombus was observed in 14% of CA patients listed for EC and mainly treated with DOAC. The acute EC success rate was high with no complication. The long-term EC success rate was acceptable (49%).

Impact of cardiac resynchronization therapy optimization inside a heart failure programme: a real-world experience.

AIMS: This study sought to describe and evaluate the impact of a routine in-hospital cardiac resynchronization therapy (CRT) programme, including comprehensive heart failure (HF) evaluation and systematic echo-guided CRT optimization. METHODS AND RESULTS: CRT implanted patients were referred for optimization programme at 3 to 12 months from implantation. The program included clinical and biological status, standardized screening for potential cause of CRT non-response and systematic echo-guided atrioventricular and interventricular delays (AVd and VVd) optimization. Initial CRT-response and improvement at 6 months post-optimization were assessed with a clinical composite score (CCS). Major HF events were tracked during 1 year after optimization. A total of 227 patients were referred for CRT optimization and enrolled (71 ± 11 years old, 77% male, LVEF 30.6 ± 7.9%), of whom 111 (48.9%) were classified as initial non-responders. Left ventricular lead dislodgement was noted in 4 patients (1.8%), and loss or ≤90% biventricular capture in 22 (9.7%), mostly due to arrhythmias. Of the 196 patients (86%) who could undergo echo-guided CRT optimization, 71 (36.2%) required VVd modification and 50/144 (34.7%) AVd modification. At 6 months post-optimization, 34.3% of the initial non-responders were improved according to the CCS, but neither AVd nor VVd echo-guided modification was significantly associated with CCS-improvement. After one-year follow-up, initial non-responders maintained a higher rate of major HF events than initial responders, with no significant difference between AVd/VVd modified or not. CONCLUSIONS: Our study supports the necessity of a close, comprehensive and multidisciplinary follow-up of CRT patients, without arguing for routine use of echo-guided CRT optimization.

Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators.

BACKGROUND: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far. OBJECTIVES: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs). METHODS: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication. CONCLUSIONS: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

Predictive value of premature atrial complex characteristics in pulmonary vein isolation for patients with paroxysmal atrial fibrillation.

BACKGROUND: Premature atrial complexes from pulmonary veins are the main triggers for atrial fibrillation in the early stages. Thus, pulmonary vein isolation is the cornerstone of catheter ablation for paroxysmal atrial fibrillation. However, the success rate remains perfectible. AIM: To assess whether premature atrial complex characteristics before catheter ablation can predict pulmonary vein isolation success in paroxysmal atrial fibrillation. METHODS: We investigated consecutive patients who underwent catheter ablation for paroxysmal atrial fibrillation from January 2013 to April 2017 in two French centres. Patients were included if they were treated with pulmonary vein isolation alone, and had 24-hour Holter electrocardiogram data before catheter ablation available and a follow-up of≥6 months. Catheter ablation success was defined as freedom from any sustained atrial arrhythmia recurrence after a 3-month blanking period following catheter ablation. RESULTS: One hundred and three patients were included; all had an acute successful pulmonary vein isolation procedure, and 34 (33%) had atrial arrhythmia recurrences during a mean follow-up of 30±15 months (group 1). Patients in group 1 presented a longer history of atrial fibrillation (71.9±65.8 vs. 42.9±48.4 months; P=0.008) compared with those who were "free from arrhythmia" (group 2). Importantly, the daily number of premature atrial complexes before catheter ablation was significantly lower in group 1 (498±1413 vs. 1493±3366 in group 2; P=0.028). A daily premature atrial complex cut-off number of<670 predicted recurrences after pulmonary vein isolation (41.1% vs. 13.3%; sensitivity 88.2%; specificity 37.7%; area under the curve 0.635; P=0.017), and was the only independent predictive criterion in the multivariable analysis (4-fold increased risk). CONCLUSION: Preprocedural premature atrial complex analysis on 24-hour Holter electrocardiogram in paroxysmal atrial fibrillation may improve patient selection for pulmonary vein isolation.

Transseptal puncture using minimally invasive echocardiography during atrial fibrillation ablation.

AIMS: To assess the usefulness of miniature transoesophageal echocardiography using a 10 F intracardiac probe (ICE-TEE) for transseptal catheterization during atrial fibrillation (AF) ablation. METHODS AND RESULTS: Intracardiac echocardiography probe was used transoesophageally in 79 consecutive patients (56 ± 11 years, 73% male) referred for AF ablation (60% paroxysmal and 38% persistent) to guide transseptal puncture. Transseptal catheterization monitored by ICE-TEE was well tolerated and successfully performed in all patients without any sedation. No mechanical oesophageal complication was noted. Moreover, the mean duration between ICE-TEE probe insertion and successful transseptal puncture was 4.5 min and the mean time of ICE-TEE was 10 min. Finally, no tamponade occurred during the AF ablation procedure. CONCLUSION: Intracardiac echocardiography-TEE is safe and well tolerated for the guidance of transseptal catheterization during AF ablation. Moreover, this technique was performed without requiring any anaesthesia.

Occurrence of significant long PR intervals in patients implanted for sinus node dysfunction and monitored with SafeR™: The PRECISE study.

BACKGROUND: Long PR intervals may increase cardiovascular complications, including atrial fibrillation. In pacemakers, the SafeR™ mode monitors PR intervals, switching from AAI to DDD when criteria for atrioventricular block are met. AIMS: The PRECISE study evaluated the incidence and predictors of long PR intervals and their association with incident atrial fibrillation after 1 year in patients implanted for sinus node dysfunction and free from significant conduction disorders at baseline. METHODS: This French, prospective, multicentre, observational trial enrolled patients implanted with a REPLY™ dual-chamber pacemaker. Pacemaker memory recorded long PR intervals (defined as first-degree atrioventricular block mode switches occurring after six consecutive PR/AR intervals≥350/450ms) and atrial fibrillation incidence (fallback mode switch>1minute/day). Predictors were identified from baseline variables (age, sex, AR and PR intervals, atrial rhythm disorder and medication) using logistic regression. RESULTS: Of 291 patients with sinus node dysfunction enrolled, 214 were free from significant conduction disorders at baseline (mean age 79±8 years; 44% men; PR/AR intervals<350/450ms). After 1 year, long PR intervals had occurred in 116 patients (54%) and atrial fibrillation in 63 patients (30%). Amiodarone was the only independent predictor of long PR interval occurrence (odds ratio 2.50, 95% confidence interval 1.20-5.21; P=0.014). There was a strong trend towards an association between long PR interval and atrial fibrillation incidence (odds ratio 1.86, 95% confidence interval 0.97-3.61; P=0.051). CONCLUSIONS: Half of the patients with pure sinus node dysfunction developed long PR intervals in the year following pacemaker implantation. Amiodarone was the only independent predictor of long PR intervals. There was a strong trend towards an association between long PR intervals and incident atrial fibrillation.

Outcome and incidence of appropriate implantable cardioverter-defibrillator therapy in patients with cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis (CA) is associated with a poor prognosis with the proposed mechanism of sudden cardiac death in the majority of patients being pulseless electrical activity. However, the incidence of ventricular arrhythmias (VA) and implantable cardioverter-defibrillator (ICD) indications in CA patients are unclear. We performed a detailed evaluation of our CA population undergoing ICD implantation and assessed appropriate ICD therapy and survival predictors. METHODS: We included consecutive patients from June 2008 to November 2014 in five centers. ICDs were systematically interrogated and clinical data recorded during follow-up. RESULTS: Forty-five patients (35 males, mean age 66±12years) with CA who underwent ICD implantation (84.4% primary prevention) were included. CA types were hereditary transthyretin in 27 patients (60%), light chain (AL) in 12 (27%) and senile in 6 (13%). After a mean follow-up of 17±14months, 12 patients (27%) had at least 1 appropriate ICD therapy occurring after 4.7±6.6months. Patients with or without ICD therapy had no significant differences in baseline characteristics, amyloidosis type, LVEF, and type of prevention although there was a trend towards a better 2D global longitudinal strain in patients with ICD therapy (P=0.08). Over the follow-up, 12 patients died (27%) and 6 underwent cardiac transplantation (13%). From multivariate analysis a worse prognosis was associated with higher NT-proBNP level (>6800pg/mL, HR=5.5[1.7-17.8]) and AL type (HR=4.9[1.5-16.3]). CONCLUSIONS: Appropriate ICD therapies are common (27%) in CA patients. No specific strong VA predictor could be identified. However, patients with advanced heart disease, especially with AL-CA, display a poorer outcome.

Uptake-1 carrier downregulates in parallel with the beta-adrenergic receptor desensitization in rat hearts chronically exposed to high levels of circulating norepinephrine: implications for cardiac neuroimaging in human cardiomyopathies.

UNLABELLED: Imaging techniques have demonstrated in various cardiomyopathies that an altered uptake of radiolabeled norepinephrine (NE) analogs may coexist with beta-adrenergic receptor downregulation, but the relationships between these 2 alterations and their mechanisms remain unclear. The aim of this study was to evaluate the hypothesis of a chronic elevation of circulating NE levels as a mechanism of decreased uptake of radiolabeled NE analogs and reduced beta-adrenergic receptor sites in the heart. METHODS: Osmotic minipumps containing either NE or NaCl were implanted intravenously in rats for 5 d. The uptake-1 function was assessed in vitro by measuring in excised hearts (3)H-NE and (123)I-metaiodobenzylguanidine ((123)I-MIBG) uptakes and uptake-1 carrier density using (3)H-mazindol binding assay. The myocardial beta-adrenergic receptor pathway was assessed in vitro by (3)H-CGP 12177 binding and measurement of adenylyl cyclase activity at baseline and under stimulation. RESULTS: A 34% decrease in (3)H-NE uptake and a 35% decrease in (123)I-MIBG uptake were found in the hearts of rats infused with the NE pump compared with that of rats infused with saline solution (P < 0.05 for both). Moreover, the uptake-1 carrier protein density was decreased by 29% (P < 0.05) and 33% (P < 0.05) in right and left ventricles, respectively, of rats infused with NE compared with those infused with saline solution. Myocardial beta-adrenergic receptor desensitization was associated with a 36% reduction in receptor density in the right ventricle (P < 0.05) and a 31% reduction in the left ventricle (P < 0.05) of rats infused with NE compared with those infused with saline solution. CONCLUSION: The decrease in myocardial beta-adrenergic receptors and radiolabeled NE analog uptake found in different cardiomyopathies using neuroimaging techniques may be related to a functional mechanism of NE-induced downregulation of both beta-adrenergic receptor and uptake-1 carrier sites.

Time course and relation to local viability of microvascular function and volume after reperfused acute myocardial infarction.

We assessed the time course of the alterations of microvascular function and myocardial perfusion, as well their relation to local inotropic reserve (IR), in 21 patients who underwent successful primary coronary angioplasty for acute myocardial infarction and in whom local myocardial dysfunction persisted at hospital discharge. Coronary flow reserve (CFR) and myocardial perfusion were assessed immediately after angioplasty, and on day 1 and day 8 by intracoronary Doppler and myocardial contrast echocardiography, respectively. Dobutamine echocardiography was performed on day 7 for assessment of local IR. After angioplasty, CFR was severely altered in patients with (n = 14) and without (n = 7) IR (1.44 +/- 0.26 and 1.36 +/- 0.21, respectively; p = NS). Among patients with IR, CFR increased significantly at day 1 (2.26 +/- 0.62, p <0.005 vs acute stage) compared with those without IR (p = NS vs acute). In contrast, the extent of microvascular obstruction as defined by contrast echocardiography remained unchanged in all patients at day 1 compared with acute measurements. Microvascular obstruction decreased at day 8 in the sole subset of patients with local IR (p <0.05 vs acute stage). In patients treated by immediate coronary angioplasty for acute myocardial infarction, subsequent improvement of myocardial perfusion is associated with preexistent recruitable microvascular function in the infarct-related artery. The presence of reversible microvascular dysfunction at the early stage after acute myocardial infarction is associated with local tissue viability in humans.

Acute pericardial effusion following atrial fibrillation ablation: characteristics and relationship with arrhythmia recurrences.

BACKGROUND: Pericardial effusion (PE) can occur during or after atrial fibrillation (AF) ablation, and may induce atrial arrhythmia. AIM: To characterize the impact of PE on arrhythmia recurrences following AF ablation. METHODS: Patients referred for a first radiofrequency AF ablation were studied prospectively. Transthoracic echocardiography was performed before and 24h after the procedure. If PE was present, transthoracic echocardiography was repeated at 1 month to evaluate PE evolution. Early arrhythmia recurrences (EARs) were defined as any arrhythmia documented within 1 month of the procedure. RESULTS: PE was diagnosed in 18/81 patients (22%); and was present in significantly more patients with persistent versus paroxysmal AF (14/40 [35%] vs 4/41 [10%]; P=0.008). PEs were mild (mean 6 ± 3mm), mainly asymptomatic (89%), and none required pericardiocentesis. Early and late arrhythmia recurrences were present in 25/81 (31%) and 29/81 (36%), respectively. The incidence of PE was significantly higher among patients with EARs versus those without (12/25 [48%] vs 6/56 [11%]; P=0.0004). By multivariable analysis, PE and duration in AF were the two independent predictors of EARs. PE incidence was similar in patients with and without late arrhythmia recurrences. At 1 month, no patients had PE on transthoracic echocardiography. CONCLUSION: PE following radiofrequency AF ablation is frequent, particularly following persistent AF ablation. This effusion is generally mild, mainly asymptomatic, and independently associated with EARs.

Importance of contractile reserve for CRT.

AIMS: To assess whether response to cardiac resynchronization therapy (CRT) is related to myocardial viability in the paced left ventricular (LV) region, evaluated by contractile reserve (CR). Non-response to CRT may partly be due to inefficient pacing by the LV lead located in a fibrotic area. METHODS AND RESULTS: Nineteen patients (64 +/- 13 years, 14 men, 9 ischaemic) with severe heart failure (EF = 27 +/- 8%, QRS = 154 +/- 25 ms) were included in the week after device implantation. Stroke volume (SV) and LV dyssynchrony (by Tissue Doppler Imaging) were successively assessed with CRT on and CRT off. Afterwards, CRT device was maintained off during dobutamine infusion to assess CR in the LV-pacing region. LV end-systolic volume (ESV) was assessed after 6 months to quantify reverse remodelling. CR in the paced LV region (n = 10, 5/9 ischaemic and 5/10 non-ischaemic) was correlated to a reduction in LV dyssynchrony under CRT (120 +/- 76 vs. 78 +/- 64 ms, P = 0.02). Conversely, LV dyssynchrony was unchanged (161 +/- 100 vs. 163 +/- 80 ms) without CR. In desynchronized patients (>65 ms, n = 15), increase in SV under CRT and changes in ESV at 6 months were +22 and -18%, respectively, when CR was present and 0% and +9%, respectively, when absent. CONCLUSION: Acute haemodynamic response and reverse remodelling under CRT require viability in the target region of LV lead.