Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.

BACKGROUND: Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. OBJECTIVES: This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. METHODS: We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. RESULTS: Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. CONCLUSIONS: DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.

Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: Systematic review and meta-analysis.

BACKGROUND: Novel pacing technologies, such as His bundle pacing (HBP) and left bundle branch area pacing (LBBaP), have emerged to maintain physiological ventricular activation. We investigated the outcomes of LBBP with HBP for patients requiring a de novo permanent pacing. METHODS AND RESULTS: Systematic review of randomized clinical trials and observational studies comparing LBBaP with HBP until March 01, 2023 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included pacing metrics, QRS duration, lead revision, procedure parameters, all-cause mortality and heart failure hospitalization (HFH). Overall, 10 studies with 1596 patients were included. Implant success rate was higher in LBBaP compared with HBP (RR 1.24, 95% CI: 1.08 to 1.42, p = .002). LBBaP was associated with lower capture threshold at implantation (mean difference (MD) -0.62 V, 95% CI: -0.74 to -0.51 V, p < .0001) and at follow-up (MD -0.74 V, 95% CI: -0.96 to -0.53, p < .0001), shorter procedure duration (MD -14.66 min, 95% CI: -23.54 to -5.78, p = .001) and shorter fluoroscopy time (MD -4.2 min, 95% CI: -8.4 to -0.0, p = .05). Compared with HBP, LBBaP was associated with a decreased risk of all-cause mortality (RR: 0.50, 95% CI: 0.33 to 0.77, p = .002) and HFH (RR: 0.57, 95% CI: 0.33 to 1.00, p = .05). No statistical differences were found in lead revisions and QRS duration before and after pacing. CONCLUSION: This meta-analysis found that LBBaP was superior to HBP regarding pacing metrics and implant success rate as an initial pacing strategy, although absence of head-to-head randomized comparison warrants caution in interpretation of the results.

Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and the European Society of Hypertension.

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium-glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.

Clinical factors related to successful or unsuccessful cardioversion in the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) randomized trial.

BACKGROUND: EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation evaluated use of nonvitamin K antagonist oral anticoagulant edoxaban vs enoxaparin-warfarin in patients with nonvalvular atrial fibrillation undergoing electrical cardioversion. HYPOTHESIS: To assess clinical factors related to successful or unsuccessful cardioversion. To evaluate whether differences in adverse events based on anticoagulation strategy may exist. METHODS: In this multicenter prospective randomized open-label blinded end-point evaluation trial, 2199 patients were randomized to edoxaban 60 mg once daily (30 mg for creatinine clearance 15-50 mL/min, weight ≤ 60 kg, and/or concomitant use of P-glycoprotein inhibitor) or enoxaparin-warfarin. Successful cardioversion was confirmed by 12-lead electrocardiography-documented sinus rhythm. RESULTS: Cardioversion was successful in 1578 patients; in 355 patients, cardioversion was unsuccessful. Male, high body weight, high body mass index (BMI), coronary artery disease, concomitant aspirin, or prior statins use were more common in patients with unsuccessful cardioversion; international normalized ratio control did not differ by cardioversion success. On multivariate analysis, gender (P < .05), body weight (P = .0196) and BMI (P = .0377) emerged as independent predictors of successful cardioversion. There were no significant differences in primary efficacy (a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death during overall study period) regardless of cardioversion success. There were no significant differences in bleeding rates, regardless of cardioversion outcome; notwithstanding low numbers, edoxaban and enoxaparin-warfarin did not differ. CONCLUSIONS: Male gender, higher mean weight and higher mean BMI were associated with unsuccessful cardioversion. Efficacy and safety outcomes were low and did not differ by cardioversion success.

Comparing TEE- vs Non-TEE-guided cardioversion of atrial fibrillation: The ENSURE-AF trial.

BACKGROUND: ENSURE-AF (NCT02072434) assessed therapy with edoxaban vs enoxaparin-warfarin in patients with nonvalvular atrial fibrillation (AF) undergoing elective electrical cardioversion (ECV). OBJECTIVES: To evaluate clinical features and primary efficacy (composite of stroke, systemic embolic events, myocardial infarction and cardiovascular mortality during study period) and safety endpoints (composite of major and clinically relevant nonmajor bleeding during on-treatment period) in patients awaiting ECV of AF with a transesophageal echocardiography (TEE)-guided vs a non-TEE-guided strategy. METHODS: In this prospective, randomized, open-label, blinded endpoint study, 2199 patients were randomized to edoxaban 60 mg once-daily (30 mg for creatinine clearance 15-50 mL/min, weight ≤60 kg and/or concomitant use of P-glycoprotein inhibitor) or enoxaparin-warfarin. Primary efficacy endpoint and safety endpoint were reported. Associates of TEE use, efficacy endpoint and safety endpoint were explored using multivariable logistic regression. RESULTS: In total, 589 patients from the edoxaban stratum and 594 from the enoxaparin-warfarin stratum were allocated to the TEE-guided strategy. Primary efficacy was similar regardless of TEE approach (P = .575). There were no significant differences in bleeding rates, regardless of TEE approach (P = .677). Independent predictors of TEE use were as follows: history of ischaemic stroke/ transient ischaemic attack, hypertension and valvular heart disease. Mean CHA2 DS2 VASc and HAS-BLED score were independent predictors of the efficacy endpoint whilst mean age was an independent predictor of the safety endpoint. CONCLUSIONS: Thromboembolic and bleeding events were not different between patients undergoing TEE-guided strategy and in those undergoing an optimized conventional anticoagulation approach for ECV of AF.

Electrical isolation of the superior vena cava by laser balloon ablation in patients with atrial fibrillation.

PURPOSE: The aim of the present study is to evaluate the feasibility and safety of SVC electrical isolation by LB ablation in patients with atrial fibrillation (AF) referred for pulmonary vein isolation (PVI). METHODS: Electrical disconnection of the SVC was attempted by LB in 13 consecutive patients (59 ± 10.5 years, 11 male) with AF following PVI. PVI was successfully achieved by standard LB in all before attempting SVC isolation. RESULTS: A laser beam was delivered with 6.3 ± 2.3 W and 8.4 ± 2.7 W (P = 0.001) during 5.38 ± 2.4 min and 9.75 ± 1.6 min (P = 0.024) to achieve SVC and PV, respectively. Isolation of the SVC by LB was accomplished in 8 patients (61%) without complications. Phrenic nerve palsy developed in 3 patients (23%), which resulted in early procedure termination before isolation. Technical problems or interposition of a pacemaker lead to prevented SVC isolation in the remaining 2 patients. After a mean follow-up of 19 ± 3 months, no patient recovered from phrenic nerve palsy. CONCLUSIONS: SVC isolation by LB is feasible but associated with a high risk of phrenic nerve palsy. Limitation of laser delivery time and power appears insufficient to prevent this complication.

Estado actual de la ablación de la fibrilación auricular / Current status on atrial fibrillation ablation

La fibrilación auricular es la arritmia más común en la práctica clínica. La ablación se considera el tratamiento de elección (indicación clase I) en los pacientes sintomáticos con recurrencias a pesar del tratamiento con fármacos antiarrítmicos. El presente artículo revisa tanto los mecanismos propuestos de esta arritmia como las diferentes metodologías de ablación con catéter y sus indicaciones.

Summary Atrial fibrillation is the most common arrhythmia in clinical practice. Catheter ablation is the treatment of choice (Class I indication) for symptomatic patients with recurrences despite antiarrhythmic drugs. The present article reviews the proposed mechanisms of this arrhythmia and the different ablation methods and indications.

La ablación de fibrilación auricular en España

Introducción: la ablación de la fibrilación auricular es uno de los procedimientos más frecuentemente realizados en las unidades de arritmias. La información de los resultados proviene de estudios prospectivos, registros multicéntricos y registros nacionales. Objetivo: evaluar la situación de la ablación de la fibrilación auricular en España a través de los datos recogidos en el Registro Español de Ablación, auspiciado por la Sección de Electrofisiología y Arritmias de la Sociedad Española de Cardiología. Métodos: los datos analizados provienen de los formularios remitidos, de forma voluntaria y anónima, por los diferentes centros hospitalarios, tanto de financiación pública como privada, durante el período 2008-2013. Cada centro fue analizado, año a año, de forma independiente. Analizamos los recursos humanos y materiales de los centros que realizaron procedimientos de ablación de fibrilación auricular durante ese período de tiempo. Asimismo, analizamos la técnica utilizada, el tipo de energía, complicaciones, etcétera. Comparamos todas las variables de forma evolutiva, año a año. Dividimos a los centros en función del número de procedimientos de ablación realizados cada año: 1-49, grupo A; 50-99, grupo B, y 100 o más, grupo C. Resultados: trescientos noventa y un centros (n=391) y 8.926 procedimientos de ablación fueron analizados. Año a año ha aumentado el número de centros que realizan ablación de fibrilación auricular y el número de procedimientos que realiza cada centro. El porcentaje de complicaciones se ha mantenido estable reduciéndose ligeramente la mortalidad. Los centros con mayor volumen tienen mayor dotación de recursos humanos y materiales. Realizan ablación de fibrilación auricular persistente con mayor frecuencia y realizan crioablación con menor frecuencia. Asimismo, estos centros tienen una menor incidencia de complicaciones. Conclusiones: la ablación de fibrilación auricular en España ha aumentado en los últimos años y presenta resultados similares a los recogidos en otros registros nacionales y multinacionales.

Utility of intracardiac echocardiography for catheter ablation of complex cardiac arrhythmias in a medium-volume training center.

AIMS AND OBJECTIVES: New electrophysiology tools like intracardiac echocardiography (ICE) might help to minimize and early detect complications during cardiac ablation procedures. The aim of the study was to assess the utility and vascular safety of ICE during catheter ablation of complex cardiac arrhythmias in a medium-volume training center. METHODS: Prospective, observational study consisted of consecutive patients who underwent catheter-based ablation of complex cardiac arrhythmias. All procedures were performed using three-dimensional electro-anatomical mapping and routine cannulation of right and left femoral veins. The ICE probe was initially positioned at the mid-level of the right atrium and properly moved to monitor different steps of the procedure and identify complications. All procedure-related vascular complications were registered. RESULTS: One hundred two patients (age 61.4 ± 13.1 years, 69 male) underwent 110 ablation procedures. Pulmonary vein isolation was the most common ablation substrate (55.4%). Ventricular tachycardia (17.2%) and left atrial flutter procedures (16.4%) were also common. The use of ICE enabled us to early initiate anticoagulation and to optimize the transseptal puncture. It also provided the capability to early detect life-threatening complications such as tamponade (3.6%), along with important information during the procedure such as exact catheter location, lesion formation, and stability during radiofrequency delivery. Such benefits were not associated with a higher number of vascular complications. CONCLUSION: The use of ICE during catheter-based ablation of complex cardiac substrates provides technical features that may decrease complications and increase accuracy while applying radiofrequency, especially in training centers where fellows start to perform complex procedures.

What is behind radiofrequency delivery at the cavo-tricuspid isthmus? / ¿Qué sucede en el istmo cavo-tricuspídeo durante la ablación con radiofrecuencia?

Catheter-based ablation of isthmus-dependent common atrial flutter results in very high success rates and almost no complications. However, bidirectional conduction block through the isthmus may be challenging in a small percentage of patients regarding the use of high power and high temperature settings during radiofrequency delivery. Anatomical and physiological circumstances may be the reason for such difficulties to achieve bidirectional block at the cavo-tricuspid isthmus. However, in the present case we show edema formation after multiple shots of radiofrequency delivery at the cavo-tricuspid isthmus, which complicates the achievement of bidirectional conduction block.

La ablación con catéter del flutter de tipo común dependiente del istmo es un procedimiento con elevada tasa de éxito y rara vez complicaciones. Sin embargo, en un pequeño porcentaje de casos puede resultar complicado conseguir el objetivo de bloquear bidireccionalmente el istmo durante el procedimiento de ablación a pesar de incrementar la potencia y temperatura del catéter de radiofrecuencia. Las características anatómicas y fisiológicas del istmo cavo-tricuspídeo pueden ocasionar dificultades en la consecución del bloqueo bidireccional. Sin embargo, en el presente caso mostramos cómo la propia aplicación de radiofrecuencia puede ocasionar edema importante tras múltiples aplicaciones con las consiguientes dificultades para conseguir el bloqueo bidireccional del istmo.

Principios básicos de las nuevas estrategias farmacológicas antiarrítmicas en fibrilación auricular / Basic mechanisms of the new antiarrhythmic drugs in atrial fibrillation

La fibrilación auricular (FA) es la arritmia crónica sostenida más frecuente en la población general. A pesar de los últimos avances tecnológicos y en el entendimiento de sus mecanismos, derivados de modelos experimentales, así como de los procedimientos de ablación en pacientes con FA, los fármacos antiarrítmicos siguen siendo la principal estrategia para la cardioversión y mantenimiento del ritmo sinusal. Nuevas generaciones de fármacos antiarrítmicos han llegado a la práctica clínica, y otros se encuentran en fase de experimentación. Los nuevos fármacos actúan de forma más específica sobre corrientes iónicas auriculares, y al mismo tiempo involucradas en el mantenimiento de la arritmia. Paralelamente, cada vez se da más importancia a la necesidad de actuar sobre el sustrato arritmogénico auricular y los factores que lo promueven, implicados en el mantenimiento a largo plazo de la arritmia (terapias upstream). La presente revisión tiene como objetivo exponer las actuales líneas de desarrollo en fármacos antiarrítmicos y terapias para prevención o retraso del remodelado auricular, con base a los conocimientos mecanísticos que hoy en día se involucran en el mantenimiento de la FA.

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. Despite of new technological breakthroughs and the understanding of the mechanisms underlying AF, based on animal models and ablation procedures in patients, the antiarrhythmic drugs remain the main therapeutic strategy to restore and maintain the sinus rhythm. New antiarrhythmic drugs are already available in the clinical practice and many others are under development. The new antiarrhythmic drugs have the capability to block atrial-specific ionic currents, which are involved in the maintenance of the arrhythmia. Parallel, increasing evidence supports the use of compounds to regulate the arrhythmogenic atrial substrate involved in the long-term maintenance of the arrhythmia (upstream therapies). This article reviews the new antiarrhythmic drugs and upstream therapies, based on the current knowledge of the mechanisms involved in the maintenance of AF.

[Ventricular tachycardia ablation guided by LocaLisa system in patients with structural heart disease]. / Ablación de taquicardias ventriculares guiada mediante sistema LocaLisa en pacientes con cardiopatía estructural.

INTRODUCTION: The ablation of ventricular tachycardia is limited by a number of factors that reduce the effectiveness of this intervention in patients with structural heart disease compared to other types of arrhythmia. Recent years have seen the development of several nonfluoroscopic navigation techniques that facilitate the mapping of complex arrhythmogenic substrates. One such technique, the LocaLisa system, has not previously been tested for the ablation of ventricular tachycardia. PATIENTS AND METHOD: A total of 32 patients with structural heart disease were treated at our center with ablation for sustained ventricular tachycardia. In 10 patients the LocaLisa system was used to visualize the catheters during the procedure. We compared the results in the LocaLisa group with those in a control group of 22 patients treated with conventional fluoroscopy-guided ablation. RESULTS: The success rate of ablation was 75% (9/12 procedures) in the LocaLisa group and 68% (17/25 procedures) in the control group (P=NS). In the LocaLisa group, mean total duration of the procedure (243 +/- 84), duration of ablation (86 +/- 56) and fluoroscopy time (46 +/- 19) did not differ significantly from those in the control group (244 +/- 72 min, 79 +/- 58 min, and 43 +/- 27 min, respectively). In the LocaLisa group the trend toward greater hemodynamic intolerance in ventricular tachycardia approached significance (42% in the LocaLisa group vs 24% in the control group, P=.05) and the number of mapping procedures performed during sinus rhythm was significantly higher in the former (33% in the LocaLisa group vs 4% in the control group, P=.03). With the LocaLisa system it was possible to locate and reposition the ablation catheter accurately at the target endocardial sites, as confirmed by electrographic recordings and fluoroscopic verification. CONCLUSIONS: The LocaLisa system helps to delineate the reentry circuit and facilitates accurate catheter repositioning in patients with structural heart disease and ventricular tachycardia.

[Recurrent ventricular fibrillation in a patient with Brugada syndrome successfully treated with procainamide]. / Fibrilación ventricular recurrente en un paciente con síndrome de Brugada: tratamiento eficaz con procainamida.

Brugada syndrome is a clinical and electrocardiographic entity characterized by ST segment elevation in the right precordial ECG leads and sudden death or syncope secondary to malignant ventricular arrhythmia, and has a high recurrence rate. We report a patient with this syndrome who had received an automatic implantable defibrillator, who presented with multiple appropriate discharges because of recurrent episodes of ventricular fibrillation. All episodes were started by a premature ventricular beat of the same morphology and coupling interval. Endovenous procainamide administration, paradoxically, was effective in preventing new episodes. The beneficial antiarrhythmic effect of procainamide in this patient is discussed.

Aspergillus aortitis after cardiac surgery.

OBJECTIVES: The aim of this study was to describe the clinical characteristics of Aspergillus aortitis in a small series of consecutive patients. BACKGROUND: Aspergillus infection of the ascending aorta after cardiopulmonary bypass surgery has rarely been reported and has always resulted in death. METHODS: Aspergillus aortitis was confirmed by pathologic and microbiologic analysis in eight men (61 +/- 8 years) of 9,375 consecutive patients who underwent cardiac surgery between 1975 and 2000. RESULTS: Patients presented with Aspergillus aortitis after aortic valve replacement (n = 5), coronary revascularization (n = 2), or both (n = 1). Initial symptoms appeared between the immediate postoperative period and up to two years after surgery. All patients had prolonged fever. Ante-mortem diagnosis was established in only three patients for whom transthoracic echocardiography was suggestive of aortic pseudoaneurysm and was confirmed by thoracic computed tomography or aortography. All patients had negative peripheral blood cultures. Seven patients died at short-term follow-up, and the one surviving patient was promptly treated by surgery and antifungal drugs. Pathologic examination confirmed Aspergillus aortitis with multi-organ dissemination without heart involvement in all patients except for two, in whom aortic valve endocarditis was found. Fungal cultures confirmed the presence of Aspergillus fumigatus in all patients. CONCLUSIONS: Aspergillus aortitis is typically found after aortic valve or coronary surgery. It commonly leads to lethal multi-organ dissemination without involvement of the intracardiac structure. This entity should be considered in patients with persistent fever and negative blood cultures after open-heart surgery involving significant aortic wall damage, irrespective of the postoperative period.