Cardiac magnetic resonance for early atrial lesion visualization post atrial fibrillation radiofrequency catheter ablation.

BACKGROUND: Incomplete atrial lesions resulting in pulmonary vein-left atrium reconnection after pulmonary vein antrum isolation (PVAI), are related to atrial fibrillation (AF) recurrence. Unfortunately, during the PVAI procedure, fluoroscopy and electroanatomic mapping cannot accurately determine the location and size of the ablation lesions in the atrial wall and this can result in incomplete PVAI lesions (PVAI-L) after radiofrequency catheter ablation (RFCA). AIM: We seek to evaluate whether cardiac magnetic resonance (CMR), immediately after RFCA of AF, can identify PVAI-L by characterizing the left atrial tissue. METHODS: Ten patients (63.1 ± 5.7 years old, 80% male) receiving a RFCA for paroxysmal AF underwent a CMR before (<1 week) and after (<1 h) the PVAI. Two-dimensional dark-blood T2-weighted short tau inversion recovery (DB-STIR), Three-dimensional inversion-recovery prepared long inversion time (3D-TWILITE) and three-dimensional late gadolinium enhancement (3D-LGE) images were performed to visualize PVAI-L. RESULTS: The PVAI-L was visible in 10 patients (100%) using 3D-TWILITE and 3D-LGE. Conversely, On DB-STIR, the ablation core of the PAVI-L could not be identified because of a diffuse high signal of the atrial wall post-PVAI. Microvascular obstruction was identified in 7 (70%) patients using 3D-LGE. CONCLUSION: CMR can visualize PVAI-L immediately after the RFCA of AF even without the use of contrast agents. Future studies are needed to understand if the use of CMR for PVAI-L detection after RFCA can improve the results of ablation procedures.

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

COMPARE LAAO: Rationale and design of the randomized controlled trial "COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy".

BACKGROUND: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking. STUDY OBJECTIVES: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications. STUDY DESIGN: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA2DS2-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands. SUMMARY: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use. NCT TRIAL NUMBER: NCT04676880.

Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC. METHODS AND RESULTS: We classified 617 definite ARVC patients (38.5 ± 15.1 years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA. CONCLUSION: The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.

The jugular approach for leadless pacing: A novel and safe alternative.

AIMS: To evaluate safety of leadless pacemaker implantation through the internal jugular vein in a larger cohort with longer follow-up. Moreover, feasibility of non-apical pacing as well as relation between pacing site and QRS duration were assessed. METHODS: Eighty Two consecutive patients, who received a leadless pacemaker though the internal jugular vein, were included. Electrical parameters were measured at regular follow-up and any complications were registered. Paced QRS interval was compared for three pacing sites, RVOT, RV mid septum, and RV apical septum. RESULTS: In all patients, the leadless pacemaker was implanted successfully. In 69 patients, the device was implanted in a non-apical position. In 71% of cases, the device could be deployed at first attempt. The median fluoroscopy time was 4.4 min (range 0.9-51) The paced QRS interval was significantly narrower for non-apical pacing sites compared to apical pacing si 156  vs. 179 ms. p = .04, respectively. During mean follow-up of 16 months (range 0-43 months), electrical parameters remained stable. Two complications occurred, which could be resolved during the implant procedure. There were no access site related complications. CONCLUSION: The jugular approach for leadless pacemaker implantation is feasible and may avoid vascular complications. It facilitates non-apical positioning of leadless pacemakers leading to a narrower paced QRS interval. The jugular approach allows for immediate post procedural ambulation.

Follow-up after hemodynamically not tolerated ventricular tachycardia in patients with midrange reduced to normal ejection fraction: A retrospective single-centre case series.

INTRODUCTION: The benefit of implantable cardioverter-defibrillator (ICD) implantation in patients with hemodynamically not tolerated ventricular tachycardia (VT) and midrange reduced to normal ejection fraction (LVEF >35%) is currently unclear. The purpose of this study was to investigate follow-up after hemodynamically not tolerated VT in patients with LVEF >35%. In addition, we aimed to find possible predictive factors to identify who will benefit from ICD implantation. METHODS: In a retrospective single-centre case series, all patients with hemodynamically not tolerated VT and LVEF >35% that underwent electrophysiological study (EPS) and/or radiofrequency VT ablation were included. RESULTS: Forty-two patients (5 women, median age 68 years) with hemodynamically not tolerated VT and LVEF >35% underwent EPS. VT ablation was performed in thirty-one patients, which was considered successful in twenty-three patients. Nineteen patients had an ICD at discharge while 23 patients were discharged without an ICD. The severity of hemodynamic compromise, LVEF and ablation success played an important role in the decision-making for ICD implantation. Six patients (14.3%) had recurrence of VT, all hemodynamically tolerated. CONCLUSIONS: In this small case series, patients with hemodynamically not tolerated VT and LVEF >35% had a relatively low recurrence rate and all recurrences were nonfatal. Based on our results, we hypothesize that the severity of hemodynamic compromise, LVEF and ablation success might modify the risk for VA recurrence. A prospective study to determine the prognostic value of these factors in patients with hemodynamically not tolerated VT and LVEF >35% is necessary.

Diagnosing arrhythmogenic right ventricular cardiomyopathy by 2010 Task Force Criteria: clinical performance and simplified practical implementation.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation. METHODS AND RESULTS: We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%). CONCLUSION: The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals.

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

Incidence and predictors of implantable cardioverter-defibrillator therapy and its complications in idiopathic ventricular fibrillation patients.

AIMS: Idiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest. Implantable cardioverter-defibrillator (ICD) implantation is currently the only treatment option. Limited data are available on the prevalence and complications of ICD therapy in these patients. We sought to investigate ICD therapy and its complications in patients with IVF. METHODS AND RESULTS: Patients were selected from a national registry of IVF patients. Patients in whom no underlying diagnosis was found during follow-up were eligible for inclusion. Recurrence of ventricular arrhythmia (VA) was derived from medical and ICD records, electrogram records of ICD therapies were used to differentiate between appropriate or inappropriate interventions. Independent predictors for appropriate ICD shock were calculated using cox regression. In 217 IVF patients, recurrence of sustained VAs occurred in 66 patients (30%) during a median follow-up period of 6.1 years. Ten patients died (4.6%). Thirty-eight patients (17.5%) experienced inappropriate ICD therapy, and 32 patients (14.7%) had device-related complications. Symptoms before cardiac arrest [hazard ratio (HR): 2.51, 95% confidence interval (CI): 1.48-4.24], signs of conduction disease (HR: 2.27, 95% CI: 1.15-4.47), and carrier of the DPP6 risk haplotype (HR: 3.24, 1.70-6.17) were identified as independent predictors of appropriate shock occurrence. CONCLUSION: Implantable cardioverter-defibrillator therapy is an effective treatment in IVF, treating recurrences of potentially lethal VAs in approximately one-third of patients during long-term follow-up. However, device-related complications and inappropriate shocks were also frequent. We found significant predictors for appropriate ICD therapy. This may imply that these patients require additional management to prevent recurrent events.

'Working to stay healthy', health-seeking behaviour in Bangladesh's urban slums: a qualitative study.

BACKGROUND: Kamrangirchar and Hazaribagh are the largest slum areas in Dhaka, Bangladesh. In 2013, Médecins Sans Frontières initiated an urban healthcare programme in these areas providing services for factory workers and responding to the sexual and reproductive health needs of young women. Little in-depth information is available on perceptions of health and health seeking behaviour in this population. We aimed to provide a better understanding of community perceptions toward health and health care in order to inform programme strategies. METHODS: In-depth interviews were conducted with women (n = 13); factory workers (n = 14); and key informants (n = 13). Participants were selected using purposive maximum variation sampling and voluntarily consented to take part. Topic guides steered participant-led interviews, which were audio-recorded, translated and transcribed from Bangla into English. By comparing cases, we identified emerging themes, patterns and relationships in the data. NVivo11© was used to sort and code the data. RESULTS: Emerging themes indicated that in Kamrangirchar and Hazaribagh, health is seen as an asset necessary for work and, thus, for survival. Residents navigate a highly fragmented health system looking for 'quick fixes' to avoid time off work, with the local pharmacy deemed 'good enough' for 'common' health issues. Health care seeking for 'serious' conditions is characterised by uncertainty, confusion, and unsatisfactory results. Decisions are made communally and shaped by collective perceptions of quality care. People with limited socio-economic capital have few options for care. 'Quality care' is perceived as comprehensive care 'under one roof,' including predictive biomedical diagnostics and effective medication, delivered through a trusting relationship with the care provider. CONCLUSIONS: Health seeking behaviour of slum dwellers of Kamrangirchar and Hazaribagh is based on competing priorities, where quick and effective care is key, focussed on the ability to work and generate income. This takes place in a fragmented healthcare system characterised by mistrust of providers, and where navigation is informed by word-of-mouth experiences of peers. Improving health in this context demands a comprehensive and integrated approach to health care delivery, with an emphasis on rapid diagnosis, effective treatment and referral, and improved trust in care providers. Health education must be developed in collaboration with the community to identify knowledge gaps, support decision-making, and be channelled through existing networks. Further research should consider the effectiveness of interventions aiming to improve the practice of pharmacists.

Identification of sarcomeric variants in probands with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC).

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and sudden death. Currently 60% of patients meeting Task Force Criteria (TFC) have an identifiable mutation in one of the desmosomal genes. As much overlap is described between other cardiomyopathies and ARVC, we examined the prevalence of rare, possibly pathogenic sarcomere variants in the ARVC population. METHODS: One hundred and thirty-seven (137) individuals meeting 2010 TFC for a diagnosis of ARVC, negative for pathogenic desmosomal variants, TMEM43, SCN5A, and PLN were screened for variants in the sarcomere genes (ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNC1, TNNI3, TNNT2, and TPM1) through either clinical or research genetic testing. RESULTS: Six probands (6/137, 4%) were found to carry rare variants in the sarcomere genes. These variants have low prevalence in controls, are predicted damaging by Polyphen-2, and some of the variants are known pathogenic hypertrophic cardiomyopathy mutations. Sarcomere variant carriers had a phenotype that did not differ significantly from desmosomal mutation carriers. As most of these probands were the only affected individuals in their families, however, segregation data are noninformative. CONCLUSION: These data show variants in the sarcomere can be identified in individuals with an ARVC phenotype. Although rare and predicted damaging, proven functional and segregational evidence that these variants can cause ARVC is lacking. Therefore, caution is warranted in interpreting these variants when identified on large next-generation sequencing panels for cardiomyopathies.

Time matters: adenosine testing immediately after pulmonary vein isolation does not substitute a waiting period.

AIMS: Adenosine testing can reveal dormant pulmonary vein (PV) conduction after PV antrum isolation (PVAI). However, the optimal timing for adenosine administration is unknown. We hypothesized that adenosine testing immediately after PVAI reliably reveals PV reconnection and thereby eliminates the need for an observation period. METHODS AND RESULTS: Fifty patients underwent PVAI. Immediately after isolation of a PV pair, adenosine was administered. Both PV pairs were separately tested. If adenosine restored PV conduction, PVs were re-isolated. During a ≥30 min observation period after immediate adenosine-guided isolation, spontaneous reconnection was assessed and reconnected PVs were re-isolated. After the observation period, adenosine testing was repeated. Immediate adenosine testing revealed dormant conduction in 10.4% of the left PVs and 16.3% of the right PVs. All PVs were successfully re-isolated. During a mean observation period of 36 ± 10 min, spontaneous reconnection occurred in 8.2% of the left and 16.3% of the right PVs. None of these PVs had shown reconnection during immediate testing. Late adenosine testing revealed dormant conduction in 12.5% of the left and 16.3% of the right PVs. In patients without reconnection during immediate adenosine testing, 14.6% of the left PVs and 30.6% of the right PVs showed either spontaneous reconnection or restored PV conduction during late adenosine testing. CONCLUSION: Adenosine testing immediately after PVAI does not reliably exclude later spontaneous or adenosine-induced PV reconnection. Adenosine testing should be performed after an appropriate observation period to reduce risk of PV reconnection.

Approach to family screening in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

AIMS: A combination of variable expression, age-related penetrance, and unpredictable arrhythmic events complicates management of relatives of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients. We aimed to (i) determine predictors of ARVD/C diagnosis and (ii) optimize arrhythmic risk stratification among first-degree relatives of ARVD/C patients. METHODS AND RESULTS: Detailed phenotypic and outcome data of 274 first-degree relatives (46% male; 36.5 ± 18.9 years) of 138 ARVD/C probands were obtained. Ninety-six (35%) relatives were diagnosed with ARVD/C according to 2010 Task Force Criteria (TFC). Siblings had a three-fold-increased risk of ARVD/C diagnosis compared with parents and children (odds ratio 3.11, P < 0.001). Multivariable logistic regression identified symptoms (P < 0.001), being a sibling (P < 0.001), the presence of a pathogenic mutation (P < 0.001), and female sex (P = 0.010) as predictors of ARVD/C diagnosis. During 6.7 ± 3.8 years of follow-up, 21 (8%) relatives experienced a sustained ventricular arrhythmia (cycle length 271 ± 48 ms). While being a sibling was a predictor of ARVD/C diagnosis, neither relatedness to the proband (P = 0.185) nor malignant family history (P = 0.347) was significantly associated with arrhythmic events. Meeting TFC independent of family history criteria had higher prognostic value for arrhythmic events than conventional 2010 TFC, which include family history [area under the receiver operating characteristic curve 0.95 (95% CI 0.93-0.97) vs. 0.85 (95% CI 0.82-0.88), P < 0.001]. CONCLUSION: One-third of first-degree relatives develop manifest ARVD/C. Siblings have highest risk of disease, even after correcting for age and sex. Fulfilment of TFC independent of family history is superior to conventional TFC for arrhythmic risk stratification of relatives.

Influence of Genotype on Structural Atrial Abnormalities and Atrial Fibrillation or Flutter in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with desmosomal mutations. Although desmosomal disruption affects both ventricles and atria, little is known about atrial involvement in ARVD/C. OBJECTIVE: To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype. METHODS: We included 71 patients who met ARVD/C Task Force Criteria and underwent cardiac magnetic resonance (CMR) imaging and molecular genetic analysis. Indexed atrial end-diastolic volume and area-length-ejection-fraction (ALEF) were evaluated on CMR and compared to controls with idiopathic right ventricular outflow tract tachycardia (n = 40). The primary outcome was occurrence of AA (atrial fibrillation or atrial flutter) during follow-up, recorded by 12-lead ECG, Holter monitoring or implantable cardioverter defibrillator (ICD) interrogation. RESULTS: Patients harbored a desmosomal plakophilin-2 (PKP2) (n = 37) or nondesmosomal phospholamban (PLN) (n = 14) mutation. In 20 subjects, no pathogenic mutation was identified. Compared to controls, right atrial (RA) volumes were reduced in PKP2 (P = 0.002) and comparable in PLN (P = 0.441) mutation carriers. In patients with no mutation identified, RA (P = 0.011) and left atrial (P = 0.034) volumes were increased. Bi-atrial ALEF showed no significant difference between the groups. AA were experienced by 27% of patients and occurred equally among PKP2 (30%) and no mutation identified patients (30%), but less among PLN mutation carriers (14%). CONCLUSION: Genotype influences atrial volume and occurrence of AA in ARVD/C. While the incidence of AA is similar in PKP2 mutation carriers and patients with no mutation identified, PKP2 mutation carriers have significantly smaller atria. This suggests a different arrhythmogenic mechanism.

Prolonged Electromechanical Interval Unmasks Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy in the Subclinical Stage.

INTRODUCTION: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by high incidence of ventricular arrhythmias. Overt ARVD/C is preceded by a subclinical stage with lack of detectable ECG and structural abnormalities. Activation delay is present before structural abnormalities and is a hallmark of arrhythmogenesis. Deformation imaging may unmask activation delay in the subclinical stage. METHODS: Three groups were compared: (1) mutation-positive definite ARVD/C-patients fulfilling 2010 Task Force criteria (TFC) (n = 44); (2) asymptomatic mutation carriers not fulfilling TFC and without history of ventricular arrhythmias (n = 31); and (3) controls (n = 30). All underwent ECG and echocardiographic deformation imaging. As a surrogate for local activation delay the electromechanical interval (EMI) was measured, defined as time between onset-QRS and onset of shortening. Arrhythmic outcome (PVC-count, VT) of asymptomatic mutation carriers was correlated with EMI and ECG TFC. RESULTS: In definite ARVD/C-patients, EMI was prolonged in all lateral RV segments. In asymptomatic mutation carriers, prolonged EMI was detected in the subtricuspid area in 14/31. Terminal activation duration ≥55 milliseconds (definition: supporting information) was the only ECG abnormality in this group (8/31). After a mean follow-up of 4.2 ± 3.1 years 10/31 asymptomatic mutation carriers experienced arrhythmic outcome. Prolonged subtricuspid EMI was the only parameter significantly associated with arrhythmogenesis during follow-up. CONCLUSION: In ARVD/C-patients, EMI prolongation was present throughout the RV. In asymptomatic mutation carriers, prolonged EMI in the subtricuspid area is often detected without any additional abnormalities. These preliminary results indicate that prolonged EMI is a new parameter unmasking activation delay in the subclinical stage and may contribute to risk stratification.

Five-year efficacy of pulmonary vein antrum isolation as a primary ablation strategy for atrial fibrillation: a single-centre cohort study.

AIMS: Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation. There is an ongoing discussion on whether and when to add substrate modification to PVAI. This study evaluates (1) long-term efficacy of PVAI as a primary ablation strategy in all patients independently from AF type and (2) predictors of arrhythmia recurrence. METHODS AND RESULTS: A total of 509 consecutive patients (mean age 57 years, 38.9% non-paroxysmal AF) with AF underwent PVAI. In redo procedures, ablation was restricted to re-pulmonary vein (PV) isolation in case of PV reconnection. If the PVs were found to be isolated, substrate modification was performed. In total, 774 procedures were performed. Mean follow-up duration after the first and last ablation was, respectively, 66 ± 23 and 55 ± 25 months. A single PVAI was sufficient in restoring and maintaining long-term sinus rhythm in 41.3% (n = 210) of patients. Multiple procedures (mean 1.5) with re-PV isolation increased long-term success to 58.3% (n = 297). Additional substrate modification (n = 70) increased success to 62.5% (n = 318). After the last ablation, 87.5% of patients experienced success or significant clinical improvement on or off antiarrhythmic drugs. The incidence of left-sided atrial flutter or atrial tachycardia was 5% after PVAI and increased to 32% after additional substrate modification. Independent predictors for arrhythmia recurrence after the last ablation were non-paroxysmal AF, female sex, body mass index, hypertension, and AF duration. CONCLUSION: Five-year freedom of atrial tachyarrhythmia could be achieved by PVAI as primary ablation strategy in 58.3% of patients. Additional substrate modification only moderately increased overall success.

Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers.

AIMS: We sought to determine the influence of genotype on clinical course and arrhythmic outcome among arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated mutation carriers. METHODS AND RESULTS: Pathogenic mutations in desmosomal and non-desmosomal genes were identified in 577 patients (241 families) from USA and Dutch ARVD/C cohorts. Patients with sudden cardiac death (SCD)/ventricular fibrillation (VF) at presentation (n = 36) were younger (median 23 vs. 36 years; P < 0.001) than those presenting with sustained monomorphic ventricular tachycardia (VT). Among 541 subjects presenting alive, over a mean follow-up of 6 ± 7 years, 12 (2%) patients died, 162 (30%) had sustained VT/VF, 78 (14%) manifested left ventricular dysfunction (EF < 55%), 28 (5%) experienced heart failure (HF), and 10 (2%) required cardiac transplantation. Patients (n = 22; 4%) with >1 mutation had significantly earlier occurrence of sustained VT/VF (mean age 28 ± 12 years), lower VT-/VF-free survival (P = 0.037), more frequent left ventricular dysfunction (29%), HF (19%) and cardiac transplantation (9%) when compared with those with only one mutation. Desmoplakin mutation carriers experienced more than four-fold occurrence of left ventricular dysfunction (40%) and HF (13%) than PKP2 carriers. Missense mutation carriers had similar death-/transplant-free survival and VT/VF penetrance (P = 0.137) when compared with those with truncating or splice site mutations. Men are more likely to be probands (P < 0.001), symptomatic (P < 0.001) and have earlier and more severe arrhythmic expression. CONCLUSIONS: Presentation with SCD/VF occurs at a significantly younger age when compared with sustained monomorphic VT. The genotype of ARVD/C mutation carriers impacts clinical course and disease expression. Male sex negatively modifies phenotypic expression.

Mutation-positive arrhythmogenic right ventricular dysplasia/cardiomyopathy: the triangle of dysplasia displaced.

INTRODUCTION: The traditional description of the Triangle of Dysplasia in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) predates genetic testing and excludes biventricular phenotypes. METHODS AND RESULTS: We analyzed Cardiac Magnetic Resonance (CMR) studies of 74 mutation-positive ARVD/C patients for regional abnormalities on a 5-segment RV and 17-segment LV model. The location of electroanatomic endo- and epicardial scar and site of successful VT ablation was recorded in 11 ARVD/C subjects. Among 54/74 (73%) subjects with abnormal CMR, the RV was abnormal in almost all (96%), and 52% had biventricular involvement. Isolated LV abnormalities were uncommon (4%). Dyskinetic basal inferior wall (94%) was the most prevalent RV abnormality, followed by basal anterior wall (87%) dyskinesis. Subepicardial fat infiltration in the posterolateral LV (80%) was the most frequent LV abnormality. Similar to CMR data, voltage maps revealed scar (<0.5 mV) in the RV basal inferior wall (100%), followed by the RV basal anterior wall (64%) and LV posterolateral wall (45%). All 16 RV VTs originated from the basal inferior wall (50%) or basal anterior wall (50%). Of 3 LV VTs, 2 localized to the posterolateral wall. In both modalities, RV apical involvement never occurred in isolation. CONCLUSION: Mutation-positive ARVD/C exhibits a previously unrecognized characteristic pattern of disease involving the basal inferior and anterior RV, and the posterolateral LV. The RV apex is only involved in advanced ARVD/C, typically as a part of global RV involvement. These results displace the RV apex from the Triangle of Dysplasia, and provide insights into the pathophysiology of ARVD/C.