Prophylactic epicardial pacemaker implantation in tricuspid valve replacement.

OBJECTIVES: Patients undergoing surgical tricuspid valve replacement (TVR) are at high risk of atrioventricular conduction disorders. Because implanting a lead through the tricuspid bioprosthesis is discouraged, the patients who undergo TVR in our centre are usually given a prophylactic epicardial pacemaker. Our aim was to assess the benefits and risks of this strategy. METHODS: Among the patients who underwent TVR with prophylactic epicardial pacemaker implantation, clinical evaluations and pacemaker reports were analysed retrospectively after surgery. The need for cardiac pacing were assessed by characterizing the atrioventricular conduction, while the risks were evaluated by listing and adjudicating post-operative events. RESULTS: A total of 80 patients were analysed (mean age was 57 ± 16 years old, 30% males). TVR was isolated in 28 (35%) patients, but most often associated with another valve surgery. In the postoperative period, heart rhythm was analysed in 59/80 patients during a median follow-up of 35 months. Cardiac pacing was needed in 46% patients: 14% had complete pacing dependency, 17% had high degree AV block, while 15% had a high ventricular pacing rate (>80%). No pre- or per-operative variables could predict cardiac pacing requirement. Post-operatively, a spontaneous heart rate >70 bpm (P = 0.02) and the presence of narrow QRS (P = 0.03) were significantly associated with a lower risk of cardiac pacing requirement. Complications related to epicardial pacemaker were documented in 2 (2.5%) patients. CONCLUSIONS: After TVR, cardiac pacing was needed in 46% of patients for post-operative atrioventricular conduction disorders. This high incidence associated with an acceptable safety profile supports a prophylactic epicardial pacing strategy for the patients undergoing TVR.

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%).

Catheter ablation of electrical storm in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Therapeutic strategies for electrical storm (ES) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) are not well defined. OBJECTIVE: The purpose of this study was to report the acute and long-term results of ventricular tachycardia (VT) radiofrequency catheter ablation (RFCA) as a treatment of ES in patients with ARVC. METHODS: This multicenter study retrospectively enrolled 23 consecutive patients with ARVC (mean age 43.6 ± 16.7 years; all men) who underwent 24 RFCA procedures for ES between 2003 and 2015. RESULTS: Thirteen patients (57%) had a previous VT RFCA procedure; 14 (61%) had right ventricular dysfunction and 7 (30%) left ventricular ejection fraction ≤ 50%. The clinical VT was inducible in 19 procedures (79%). Epicardial ablation was performed in 4 procedures (17%). The median number of targeted VTs was 1 (range 1-6). Complete acute success (no VT inducible) was achieved in 11 procedures (46%) and partial acute success (clinical VT nor inducible) in 11 (46%). After a median follow-up of 3.9 years (range 1 month-10 years), ES recurred in 2 patients and end-stage heart failure developed in 4 (17%), leading to 1 death and 3 heart transplantations. At 1-year follow-up, the probability of freedom from VT recurrence was 75% and did not significantly predict long-term survival. At the last evaluation, 8 patients (35%) were free of non-ß-blocker antiarrhythmic drugs as compared with 1 (4%) at baseline (P = .02). CONCLUSION: Catheter ablation was efficient to prevent ES recurrence in patients with ARVC. However, these patients were at high risk of evolution toward ARVC-related heart failure that was not associated with VT recurrence.

High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene. METHODS AND RESULTS: Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005). CONCLUSIONS: In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.

Management of atrial fibrillation in patients with rheumatic mitral stenosis.

Atrial fibrillation (AF) is frequent in patients with rheumatic mitral stenosis (MS). Pressure overload leads to marked structural and electrical remodelling of left atrium. The frequency of persistent AF increases with age and paroxysmal, asymptomatic, AF seems even more frequent. The occurrence of AF worsens the haemodynamic tolerance of MS and markedly increases the risk of thromboembolic events. AF has a negative impact on the natural history of MS and on its outcome after commissurotomy. The respective indications of rhythm and rate control should be adapted to patient characteristics, particularly the consequences of MS, and take into account the high risk of recurrence of AF. Oral anticoagulant therapy is mandatory when AF complicates MS, regardless of its severity and CHA2DS2-VASc score. Non-vitamin K antagonists oral anticoagulants are not recommended in moderate-to-severe MS due to the lack of data. Percutaneous mitral commissurotomy does not appear to prevent the occurrence of AF in MS but should be considered as the first-line therapy when AF is associated with severe symptomatic MS, followed by the discussion of cardioversion or ablation. AF ablation should be considered in patients with mitral disease requiring intervention, but the ideal timing and techniques are difficult to determine due to the lack of appropriate specific randomised trials in patients with MS.

High mass (>18g) of late gadolinium enhancement on CMR imaging is associated with major cardiac events on long-term outcome in patients with biopsy-proven extracardiac sarcoidosis.

BACKGROUND: Cardiac involvement is the most important cause of mortality in patients with systemic sarcoidosis. Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) has been shown to be a predictor of major cardiovascular adverse events (MACE) in the setting of systemic sarcoidosis. We sought to evaluate the relationship between LGE mass and adverse long-term outcome in patients with biopsy-proven extracardiac sarcoidosis. METHODS: Between 2001 and 2013, 197 consecutive patients with suspected cardiac sarcoidosis were identified in our institution database. Of them, 56 patients have had biopsy-proven extracardiac sarcoidosis and represented our studied population. Patients were divided into two groups based on LGE mass by a median value (mild LGE<18g, high LGE>18g) for comparison of MACE. RESULTS: Twenty-eight patients had a high mass of LGE. Of them, 15 (54%) experienced MACE (OR=31.15, 95% CI 3.7-262). Except for 1 patient, no patient with mild LGE presented with any MACE during follow-up (median of 32months). Patients with high LGE had lower CMR-derived left (53.6±14.9 vs. 62.2±6.7, p<0.01) and right (49.1±11.5 vs. 56.4±9.2, p<0.05) ventricular ejection fractions. LGE mass of 18g discriminated patients with and without MACE (93% sensitivity, 88% specificity, AUC=0.972). LGE mass was the only independent predictor of MACE on multivariate Cox analysis adjusted (OR=1.7, 95% CI 1.06 to 2.72, p=0.03). CONCLUSION: In biopsy-proven extracardiac sarcoidosis patients, a high mass of LGE >18g was associated with MACE.

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.

Prevalence and significance of rare RYR2 variants in arrhythmogenic right ventricular cardiomyopathy/dysplasia: results of a systematic screening.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. Ryanodine receptor 2 (RYR2) gene mutations usually cause catecholaminergic polymorphic ventricular tachycardia but have been associated with a peculiar phenotype named ARVC2. OBJECTIVE: We aimed to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population. METHODS: We analyzed the whole RYR2 coding sequence by Sanger sequencing in 64 ARVC/D probands without desmosomal gene mutations. RESULTS: We have identified 6 rare missense variants: p.P1583S, p.A2213S, p.G2367R, p.Y2932H, p.V3219M, and p.L4670V. It corresponds to a 9% prevalence of rare RYR2 variants in the ARVC/D population (6 of 64 probands), which is significantly higher than the estimated frequency of rare RYR2 variants in controls (Fisher exact test, P = .03). Phenotypes associated with RYR2 variants were similar to desmosome-related ARVC/D, associating typical electrocardiographic abnormalities at rest, frequent monomorphic ventricular tachycardia, right ventricular dilatation, wall motion abnormalities, and fibrofatty replacement when histopathological examination was available. CONCLUSION: In this first systematic screening of the whole coding region of the RYR2 gene in a large ARVC/D cohort without mutation in desmosomal genes, we show that putative RYR2 mutations are frequent (9% of ARVC/D probands) and are associated with a conventional phenotype of ARVC/D, which is in contrast with previous findings. The results support the role of the RYR2 gene in conventional ARVC/D.

Microvolt T-wave alternans in short QT syndrome.

BACKGROUND: T-wave alternans (TWA) is an accepted marker of risk for malignant ventricular arrhythmias, for which prognosis value has been established in different populations. Short QT syndrome (SQTS) is a very rare primary electrical disease carrying the risk of ventricular fibrillation. TWA in SQTS has not been evaluated yet. METHODS: Thirteen patients with SQTS (QT = 308 ± 16 ms, QTc = 329 ± 10 ms, heart rate = 69 ± 8 beats/min) underwent microvolt TWA measurement using spectral analysis. TWA testing was performed using Heartwave II (Cambridge Heart™, Inc., Bedford, MA, USA) during bicycle exercice and classified as negative, positive, or indeterminate according to the published standards for clinical interpretation. RESULTS: Twelve patients were male (mean age 23 ± 5 years). Five were asymptomatic, three presented with aborted sudden cardiac death, and five with unexplained syncope. Six patients belonged to two unrelated families, while familial cases of SQTS were present for two other patients. A familial history of sudden death (SD) was present for seven patients. Ventricular fibrillation was inducible in three patients. Four patients were implanted with an implantable cardioverter-defibrillator and one presented with polymorphic ventricular tachycardia during follow-up. TWA was negative in each but one patient (indeterminate). Maximal negative heart rate was 118 ± 12 beats/min. Patients with previous SD displayed significant shorter QT and higher resting heart rate compared to the remaining cases. CONCLUSIONS: TWA testing is negative in 12 of 13 SQTS patients, even in the symptomatic or inducible ones. Measurement of TWA using conventional protocol and criteria for risk stratification in SQTS seems therefore useless.

The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands.

AIMS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmic disorder with a highly malignant clinical course. Exercise-stress test is the first-line approach to diagnose suspected individuals. We sought to elucidate the value of exercise-stress test for predicting mutations and future cardiac events in CPVT-family relatives. METHODS AND RESULTS: The present study included 67 asymptomatic relatives (24 ± 15 years) of 17 genetically positive CPVT probands, who underwent exercise-stress test without any medication and genetic testing. Exercise-stress test, which was considered positive with the induction of ventricular tachycardia or premature ventricular contractions consisting of bigeminy or couplets, was positive in 17 relatives (25%). Genetic analysis disclosed mutations in 16 of these 17 relatives (94%) and in 16 of the 50 relatives (32%) with negative exercise-stress test; the sensitivity and specificity for a positive genotype were 50 and 97%, respectively (P< 0.001). Among 32 mutation carriers, cardiac events occurred in 7 of the 16 relatives with positive and 2 of the 16 relatives with negative exercise-stress test during the follow-up period of 9.6 ± 3.8 years, and four with positive and two with negative stress test were not on regular beta-blocker treatment at these events. In the 16 relatives with positive stress test, those on beta-blocker treatment demonstrated a trend of lower cardiac event rate (Log-rank P= 0.054). CONCLUSION: In asymptomatic relatives of CPVT probands, exercise-stress test can be used as a simple diagnostic tool. Nevertheless, because of the low sensitivity for predicting mutations and future cardiac events in those with negative stress test, genetic analysis should be performed to improve patient management.

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.

AIMS: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION: This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.

Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes.

BACKGROUND: The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported. METHODS AND RESULTS: Seven patients (4 men; age, 38+/-7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12+/-6 minutes of radiofrequency applications. During a follow-up of 17+/-17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats. CONCLUSIONS: Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.