Massimiliano Marini

Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies

OBJECTIVES The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. BACKGROUND Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases. METHODS Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype. RESULTS Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for >or=10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death. CONCLUSIONS Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.

Reduced fluoroscopy exposure during ablation of atrial fibrillation using a novel electroanatomical navigation system: a multicentre experience.

AIMS Catheter ablation of atrial fibrillation (AF) focuses on pulmonary vein (PV) ablation with or without additional atrial substrate modification. These procedures require significant fluoroscopy exposure. A new 3D non-fluoroscopic navigation system (CARTO(®) 3 System, Biosense Webster, CA, USA) that allows precise location visualization of diagnostic and ablation catheters was evaluated for its impact on fluoroscopic exposure during AF ablation procedures. METHODS AND RESULTS Two groups of patients were treated by our centres for drug refractory AF. One group was treated using the new CARTO(®) 3 system to guide catheter ablation (Group A, 117 patients). The other group was treated using the CARTO(®) XP system (Biosense Webster) 3 months previously (Group B, 123 patients). For both groups, circumferential PV ostia ablation was performed; PV isolation was validated using a circular catheter placed at each ostium. There was no difference in any clinical characteristics (age, sex, AF type, left atrium diameter and volume, and heart disease) among the two study groups. The mean number of PVs identified and isolated per patient was similar in both groups, as were the mean procedural duration and radiofrequency time. However, mean fluoroscopic time was significantly reduced in Group A (15.9±12.3 min) as compared with Group B (26±15.1 min) (P < 0.001). CONCLUSION This multicentre observational study demonstrates a significant reduction of fluoroscopy exposure using a new 3D non-fluoroscopic mapping system to guide AF catheter ablation.

Acute Atrial Dilatation Slows Conduction and Increases AF Vulnerability in the Human Atrium

Stretch Slows Conduction in the Human Atrium. Introduction: The mechanisms by which atrial stretch favors the development of a substrate for atrial fibrillation (AF) are not fully understood. In this study, the role of stretch‐induced conduction changes in the creation of a proarrhythmic substrate has been investigated by quantifying the spatial distribution of local conduction velocities (CVs) in the human atrium during acute atrial dilatation.

Autosomal Recessive Atrial Dilated Cardiomyopathy With Standstill Evolution Associated With Mutation of Natriuretic Peptide Precursor A

Background—Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy. Methods and Results—We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide. Conclusions—Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.

Anatomic Localization of Rapid Repetitive Sources in Persistent Atrial Fibrillation: Fusion of Biatrial CT Images With Wave Similarity/Cycle Length Maps

OBJECTIVES The aim of this study was to investigate the anatomic distribution of critical sources in patients with atrial fibrillation (AF) by fusion of biatrial computed tomography (CT) images with cycle length (CL) and wave similarity (WS) maps. BACKGROUND Experimental and clinical studies show that atrial fibrillation (AF) may originate from rapid and repetitive (RR) sources of activation. Localization of RR sources may be crucial for an effective ablation treatment. Atrial electrograms showing rapid and repetitive activations can be identified by combining WS and CL analysis. METHODS Patients with persistent AF underwent biatrial electroanatomic mapping and pre-procedural CT cardiac imaging. WS and CL maps were constructed in 17 patients by calculating the degree of repetitiveness of activation waveforms (similarity index [S]) and the cycle length at each atrial site. WS/CL maps were then integrated with biatrial 3-dimensional CT reconstructions by a stochastic approach. RESULTS Repetitive sources of activation (S ≥ 0.5) were present in most patients with persistent AF (94%) and were mainly located at the pulmonary veins (82% of patients), at the superior caval vein (41%), on the anterior wall of the right atrium (23%), and at the left atrial appendage (23%). Potential driver sources showing both rapid and repetitive activations (CL = 140.7 ± 25.1 ms, S = 0.65 ± 0.15) were present only in a subset of patients (65%) and were confined to the pulmonary vein region (47% of patients) and left atrial appendage (12%). Differently, the repetitive activity of the superior caval vein was characterized by a slow activation rate (CL = 184.7 ± 14.6 ms). CONCLUSIONS The identification and localization of RR sources is feasible by fusion of biatrial anatomic images with WS/CL maps. Potential driver sources are present only in a subset of patients with persistent AF and are mainly located in the pulmonary vein region.

Implantation of a biventricular implantable cardioverter-defibrillator guided by an electroanatomic mapping system

Aims The aim of this study is to show the feasibility of a biventricular implantable cardioverter-defibrillator [cardiac resynchronization therapy (CRT)–ICD] implantation using an electroanatomic navigation system and a low dose of fluoroscopy. Here four case reports of patients affected by dilated cardiomyopathy, who underwent cardiac resynchronization therapy, are described. Methods and results During 2010, four patients were admitted to our Cardiology Department for implantation of an CRT–ICD device in primary prevention. All had an ejection fraction of <35% and were in New York Heart Association class III despite optimal medical therapy. The implantations were performed using the EnSite NavX system. All the leads were positioned in the cardiac chambers utilizing the three-dimensional navigation system and only using X-ray to check that the leads had been positioned correctly. To our knowledge, these cases are the first use of an electroanatomic system for implantation of an CRT–ICD device and in all four cases the cannulation of the coronary sinus (CS) was performed only using the mapping system. Electroanatomic navigation made it possible to minimize X-ray exposure during the implantation of the CRT–ICD device; in addition, the mapping system was used to choose the optimum position of the CS catheter using as reference the maximum activation delay between the two ventricles. Conclusions The NavX system shows great potential during the implantation of an CRT–ICD device. It seems to be feasible, safe, and extremely beneficial in terms of a reduction in X-ray exposure. Furthermore, there is benefit of more detailed information and accuracy during the CS lead placement.

Electroanatomic Mapping and Late Gadolinium Enhancement MRI in a Genetic Model of Arrhythmogenic Atrial Cardiomyopathy

Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In this study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy.

Rationale and design of the NO-PARTY trial: near-zero fluoroscopic exposure during catheter ablation of supraventricular arrhythmias in young patients

INTRODUCTION Radiofrequency catheter ablation is the mainstay of therapy for supraventricular tachyarrhythmias. Conventional radiofrequency catheter ablation requires the use of fluoroscopy, thus exposing patients to ionising radiation. The feasibility and safety of non-fluoroscopic radiofrequency catheter ablation has been recently reported in a wide range of supraventricular tachyarrhythmias using the EnSite NavX™ mapping system. The NO-PARTY is a multi-centre, randomised controlled trial designed to test the hypothesis that catheter ablation of supraventricular tachyarrhythmias guided by the EnSite NavX™ mapping system results in a clinically significant reduction in exposure to ionising radiation compared with conventional catheter ablation. METHODS The study will randomise 210 patients undergoing catheter ablation of supraventricular tachyarrhythmias to either a conventional ablation technique or one guided by the EnSite NavX™ mapping system. The primary end-point is the reduction of the radiation dose to the patient. Secondary end-points include procedural success, reduction of the radiation dose to the operator, and a cost-effectiveness analysis. In a subgroup of patients, we will also evaluate the radiobiological effectiveness of dose reduction by assessing acute chromosomal DNA damage in peripheral blood lymphocytes. CONCLUSIONS NO-PARTY will determine whether radiofrequency catheter ablation of supraventricular tachyarrhythmias guided by the EnSite NavX™ mapping system is a suitable and cost-effective approach to achieve a clinically significant reduction in ionising radiation exposure for both patient and operator.

Role of multidetector computed tomography in the anatomical definition of the left atrium-pulmonary vein complex in patients with atrial fibrillation. Personal experience and pictorial assay

PurposeThis study aimed to illustrate the typical anatomical pattern and anatomical variants of the left atrium-pulmonary vein (LA-PV) complex studied by 16-slice multidetector computed tomography (MDCT) in a population of patients with atrial fibrillation (AF) undergoing percutaneous transcatheter left atrial ablation. Accurate knowledge of this anatomical region is fundamental for increasing the efficiency, efficacy and accuracy of the procedure and for reducing the risk of complications.Materials and methodsFrom January 2004 to March 2007, we studied 75 patients (57 men, 18 women) affected by paroxysmal and chronic AF by using MDCT. In 63 patients, the MDCT examination was performed using retrospective cardiac electrocardiographic (ECG) gating and dose modulation, with reconstructions performed at 75% of R-R interval. In the remaining 12 patients, ECG gating was not possible due to high-frequency AF.ResultsWe identified 286 PV: 157 right and 129 left. On the right side, eight PV were supernumerary and one was a common trunk, whereas on the left side, we found 22 common trunks and one supernumerary vein. In 61.3% of patients, the anatomical pattern was typical (two right and two left PV). In the remaining 38.7%, it was atypical [two right PV-left common trunk (26.6%); three right PV-two left PV (6.7%); three right PV-left common trunk (2.6%); three right PV-three left PV (1.3%); right common trunk-two left PV (1.3%)]. MDCT identified branching of the right inferior PV in 94.5%, of the right superior PV in 75.6%, of the left superior PV in 7.5% and of the left inferior PV in 7.5%; 3/8 of the right supernumerary veins presented branching. With respect to the left PV ostia, the position of the orifice of the 74 recognised appendages was high in 85.1%, intermediate in 12.1% and low in 2.8%. There was no association between PV anatomical variants and clinical presentation of AF (paroxysmal or chronic).ConclusionsMDCT represents a fundamental diagnostic imaging tool in the anatomical definition of the LA-PV complex, which is characterised by considerable variability. Radiologists must be familiar with the anatomical variants and help the referring interventional electrophysiologist understand their importance.RiassuntoObiettivoIllustrare quadro tipico e varianti anatomiche del complesso atrio sinistro-vene polmonari (AS-VP) studiato con TC spirale multidetettore a 16 strati (TCMD) in una popolazione di pazienti affetti da fibrillazione atriale (FA) in attesa di essere sottoposti ad intervento di ablazione trans-catetere in atrio sinistro. La precisa conoscenza di questa regione anatomica è indispensabile per realizzare con maggiore efficacia, efficienza ed accuratezza la procedura terapeutica, riducendo le complicanze.Materiali e metodiNel periodo compreso tra gennaio 2004 e marzo 2007 sono stati valutati con TCMD 75 pazienti (57 maschi e 18 femmine) affetti da FA parossistica e cronica. In 63 pazienti l’indagine TCMD è stata effettuata con gating cardiaco retrospettivo e modulazione della dose, ricostruendo la finestra temporale corrispondente al 75% dell’intervallo RR dell’ECG. Nei restanti 12 pazienti non è stato possibile utilizzare il gating cardiaco per la presenza di FA ad alta frequenza.RisultatiNei pazienti studiati sono state identificate 286 VP, 157 a destra e 129 a sinistra. A destra sono state riconosciute 8 vene soprannumerarie e 1 tronco comune mentre a sinistra 22 tronchi comuni e 1 vena soprannumeraria. Nel 61,3% dei pazienti il quadro inadeanatomico era tipico (2 VP destre e sinistre) e atipico nel restante 38,7% dei pazienti (26,6% 2 VP destre-tronco comune sinistro; 6,7% 3 VP destre-2 VP sinistre; 2,6% 3 VP destre-tronco comune sinistro; 1,3% 3 VP destre-3 VP sinistre; 1,3% tronco comune destro-2 VP sinistre). Nella definizione dei rami di confluenza pre-ostiali delle VP (branching), la TCMD ha identificato il branching della VP inferiore destra nel 94,5% dei casi, della VP superiore destra nel 75,6%, della VP superiore sinistra nel 7,5% e della VP inferiore sinistra nel 7,5%; 3/8 delle vene soprannumerarie destre presentavano branching. Rispetto all’ostio delle VP sinistre, l’orifizio delle 74 auricole identificate era in posizione alta nel 85,1% dei casi, in posizione intermedia nel 12,1% e bassa nel 2,8%. Non sono state rilevate associazioni tra varianti anatomiche delle VP e presentazione clinica della FA (parossistica o cronica).ConclusioniLa TCMD è uno strumento diagnostico fondamentale per definire l’anatomia del complesso AS-VP, la cui variabilità anatomica è elevata. Il radiologo deve conoscere le varianti anatomiche e farne capire l’importanza all’elettrofisiologo interventista.

The logical operator map identifies novel candidate markers for critical sites in patients with atrial fibrillation.

The identification of suitable markers for critical patterns during atrial fibrillation (AF) may be crucial to guide an effective ablation treatment. Single parameter maps, based on dominant frequency and complex fractionated electrograms, have been proposed as a tool for electrogram-guided ablation, however the specificity of these markers is debated. Experimental studies suggest that AF critical patterns may be identified on the basis of specific rate and organization features, where rapid organized and rapid fragmented activities characterize respectively localized sources and critical substrates. In this paper we introduce the logical operator map, a novel mapping tool for a point-by-point identification and localization of AF critical sites. Based on advanced signal and image processing techniques, the approach combines in a single map electrogram-derived rate and organization features with tomographic anatomical detail. The construction of the anatomically-detailed logical operator map is based on the time-domain estimation of atrial rate and organization in terms of cycle length and wave-similarity, the logical combination of these indexes to obtain suitable markers of critical sites, and the multimodal integration of electrophysiological and anatomical information by segmentation and registration techniques. Logical operator maps were constructed in 14 patients with persistent AF, showing the capability of the combined rate and organization markers to identify with high selectivity the subset of electrograms associated with localized sources and critical substrates. The precise anatomical localization of these critical sites revealed the confinement of rapid organized sources in the left atrium with organization and rate gradients towards the surrounding tissue, and the presence of rapid fragmented electrograms in proximity of the sources. By merging in a single map the most relevant electrophysiological and anatomical features of the AF process, the logical operator map may have significant clinical impact as a direct, comprehensive tool to understand arrhythmia mechanisms in the single patient and guide more conservative, step-wise ablation.