**3.4.2 Safety**

376 Myocarditis

Adequate catheter contact should be confirmed by concordant catheter tip motion with the cardiac silhouettes on fluoroscopy and by adherence of voltage map to angiographic right ventricular shape. To avoid low voltage recordings due to poor contact, the following tools can be used: 1) the signal has to satisfy 3 stability criteria automatically detected by CARTO system in terms of cycle length, local activation time and beat-to-beat difference of the location of the catheter (<2%, <3 ms, and <4 mm, respectively); 2) both bipolar and unipolar signals are simultaneously acquired to confirm true catheter contact through the analysis of local electrogram (in particular the shape of the unipolar electrogram); 3) in the presence of a low voltage area, at least 3 additional points should be acquired in the same site to confirm the reproducibility of the voltage measurement. The anatomical distribution of the pathological areas is evaluated dividing the right ventricular voltage map into five segments: outflow tract, free (anterolateral) wall, inferior and posterior basal segments,

The main limitation of endomyocardial biopsy to provide a specific diagnosis in patients with ventricular arrhythmias caused by focal myocardial diseases, (i.e. myocarditis or initial forms of arrhythmogenic right ventricular cardiomyopathy), is represented by the sampling error due to the lack of an effective guide in selecting ventricular areas where to perform biopsies. In the last years, after the development of 3D-EAM systems, we introduced a new technique for the execution of endomyocardial biopsies in patients with ventricular

The new approach is aimed to perform endomyocardial biopsies in the ventricular segments presenting electrical abnormalities at electroanatomical mapping. When using the CARTO system, once the electroanatomical map is completed, the mapping catheter is placed in a region of interest of the ventricular wall and the preformed sheath is positioned closed to the catheter tip (Figure 4). Endomyocardial biopsy is then performed in the area with abnormal electrical properties as showed by the map. As previously mentioned, another approach we tested requires the electrical connection of the bioptome to the mapping system: the presence of the metallic jaws makes the bioptome similar to a mapping catheter and it is therefore visualized in the 3D electroanatomical map of the ventricle. In this case, the site of biopsy can be chosen "live", directly mapping the ventricular wall with the bioptome (Figure 4). The latter technique can be adopted when using the NavX mapping system. With both systems we usually performed ventricular angiography before the execution of ventricular mapping, in order to improve the anatomical accuracy of the map, as angiography still represents the gold standard to detect wall motion abnormalities and

Although no data on specificity and sensitivity of 3D-EAM-guided vs. conventional technique are currently available in literature, it is reasonable that obtaining myocardial samples from areas of the ventricular wall presenting electrical abnormalities will probably reduce the sampling error and the need for multiple biopsies from the same patient (See below). Moreover the combination of 3D-EAM with other imaging tools such as cardiac MRI would further improve our ability to obtain samples from selected regions that present

apex, and interventricular septum.

arrhythmias (Pieroni et al., 2009).

small aneurysms of the right venticle.

structural, functional and electrical abnormalities.

**3.4.1 Technique** 

**3.4 Electroanatomic mapping-guided endomyocardial biopsy** 

The execution of endomyocardial biopsies drawing myocardial samples from non conventional sites, including the right ventricular free-wall and outflow tract do not increase the risks of the procedure. Since 2006 we perfomed 3D-EAM-guided endomyocardial biopsy in more than sixty patients with about 400 samples obtained. In order to evaluate the safety of this new approach we prospectively analysed the rate of major and minor complications through continuous ECG monitoring during the procedure, ECG and 2D-echocardiography at the end the procedure and after 3 and 6 hours. Major complications included pericardial tamponade with need for pericardiocentesis, hemo- and pneumopericardium, permanent atrioventricular block requiring permanent pacemaker implantation, myocardial infarction, transient cerebral ischemic attack and stroke, severe valvular damage, and death, whereas minor complications included transient chest pain, transient ECG abnormalities, transient arrhythmias, transient hypotension, and small pericardial effusions. The major complication rate was 0% and the minor complication rate was 4.5%: minor complications were represented by small pericardial effusions in 2 patients and chest pain in 1. These rates are in line with those observed in a recent large two-centers study including 755 procedures (right, left and biventricular endomyocardial biopsy) and reporting a major and minor complication rate of 0.82% and 5.1% respectively for right ventricular endomyocardial biopsy (Yilmaz et al., 2010). In literature another study in which 3D-EAM-guided endomyocardial biopsy was performed in 22 patients, reported a higher rate of major complications (1.1%) and minor complications (5.7%), thus suggesting that the expertise of the operators besides the clinical condition and the underlying disorder may influence the safety of the procedure (Avella et al., 2008).

Myocarditis Presenting with Ventricular Arrhythmias:

events during the same time (Figure 6).

Role of Electroanatomical Mapping-Guided Endomyocardial Biopsy in Differential Diagnosis 379

On the basis of clinical and histological features, a cardioverter defibrillator was implanted in 13 patients with biopsy-proven ARVC and in 1 patient only with myocarditis. At a mean follow-up of 21±8 months, 7 (47%) patients with ARVC experienced recurrence of symptomatic sustained ventricular arrhythmias with appropriate defibrillator intervention in all cases. All patients with myocarditis remained asymptomatic and free from arrhythmic events. Our study was the first to demonstrate that 3D-EAM-guided EMB may allow obtaining a differential diagnosis in patients with otherwise undistiguishable clinical, arrhythmic and imaging features. In addition our study clearly showed that patients with similar arrhythmic presentation may have a dramatically different prognosis in terms of arrhythmias' recurrence according to the underlying disorders, as only 53% of biopsyproven ARVC patients remained free from arrhythmias at a mean follow-up of 21±8 months years, while no patients with biopsy-proven myocarditis experienced major arrhythmic

Fig. 6. Kaplan-Meier analysis of arrhythmic event-free survival depending on the

In a more recent study (Pieroni et al unpublished data) we performed 3D-EAM-guided EMB in a series of elite competitive athletes presenting with sustained ventricular arrhythmias. We studied 13 consecutive competitive athletes with evidence of sustained ventricular arrhythmias within the previous six months on 12-lead ECG, 24-hour Holter ECG or ECG exercise testing and who were judged as having a structurally normal heart after a thorough non-invasive evaluation, including signal-averaged electrocardiogram, transthoracic echocardiogram and CMR. Depending on the presumed site of arrhythmias origin according to 12-lead ECG criteria, patients underwent right or left ventricular 3D-EAM and 3D-EAM-guided endomyocardial biopsy. Twelve (92%) patients presented at least 1 lowvoltage region at 3D-EAM, while the histologic diagnosis was active myocarditis in 7 patients, and of arrhythmogenic RV cardiomyopathy in 5. In one patient the histological evidence of contraction-band necrosis allowed to unmask caffeine and ephedrine abuse. The identification of the underlying histological substrate in patients with ventricular arrhythmias may be relevant also when radiofrequency catheter ablation (RFCA) is

histological findings (Modified from Pieroni et al. 2009).
