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The prediction and prevention of sudden cardiac death is the philosopher’s stone of clinical cardiac electrophysiology. Sports can act as triggers of fatal arrhythmias and therefore it is essential to promptly frame the athlete at risk and to carefully evaluate the suitability for both competitive and recreational sports activity. A history of syncope or palpitations, the presence of premature ventricular complexes or more complex arrhythmias, a reduced left ventricular systolic function, or the presence of known or familiar heart disease should prompt a thorough evaluation with second level examinations. In this regard, cardiac magnetic resonance and electrophysiological study play important roles in the diagnostic work-up. The role of genetics is increasing both in cardiomyopathies and in channelopathies, and a careful evaluation must be focused on genotype positive/phenotype negative subjects. In addition to being a trigger for fatal arrhythmias in certain cardiomyopathies, sports also play a role in the progression of the disease itself, especially in the case arrhythmogenic right ventricular cardiomyopathy. In this paper, we review the latest European guidelines on sport cardiology in patients with cardiovascular diseases, focusing on arrhythmic risk stratification and the management of cardiomyopathies and channelopathies.

Background ventricular Arrhythmias (VAs) are a common clinical problem and a critical issue with regards to sports" eligibility in athletes. Although VAs can be considered a benign feature of the athlete’s heart adaptive phenotype, they may also be the only clinical manifestation of a concealed cardiomyopathy, potentially heralding sudden cardiac death (SCD) during sports activity. Purpose to evaluate the diagnostic contribution and the implications for sports eligibility assessment of a thorough non-invasive and invasive work-up including electrophysiology study (EPS), electroanatomical mapping (EAM) and endomyocardial biopsy (EMB) in athletes with complex VAs and to derive a multiparametric risk score in order to easily predict structural heart diseases’ diagnosis. Methods we conducted a prospective, single-arm, open-label single center, observational study. All consecutive athletes presenting for evaluation at our institution after being disqualified from participating in sports due to complex VAs were enrolled. The athletes underwent a baseline non-invasive diagnostic protocol with transthoracic echocardiogram and gadolinium enhanced cardiac magnetic resonance imaging (cMRI). Subsequently EPS, EAM and EAM-guided EMB were performed if deemed necessary. Sports eligibility status was re-assessed at 6 months’ follow-up. A multivariable logistic regression model was built, considering cMRI as the gold standard exam. Results after diagnostic evaluation, 55 subjects (26.4%) had a diagnosis of heart disease, most commonly myocarditis (n = 27) and arrhythmogenic right ventricular cardiomyopathy (ARVC, n = 16). After 6 months, 100 athletes (48.1%) were judged eligible to participate in competitive sports and 46 subjects (22.1%) were deemed eligible to participate in non-competitive sports. On multivariable logistic-regression analysis, abnormalities on ECG (OR 5.3) or on echocardiogram (OR 3.7), sustained VA inducibility on EPS (OR 17.7) and low-voltage areas on EAM (OR 7.7) proved all predictive of concealed structural heart diseases’ diagnosis. We derived two simple risk scores: a 40-points risk score and an 8-points risk score (obtained by weighing each variable according to the regression model’s ORs). Both these risk scores’ performance proved very good (AUC = 0.856 for the 40-points score and AUC = 0.852 for the 8-points score, figure 1). Conclusions approximately 1/4 of athletes presenting with complex VAs have a concealed heart disease, most commonly myocarditis or ARVC. ECG, echocardiogram and EAM abnormalities and sustained VAs inducibility on EPS are predictive of structural heart diseases’ detection. Therefore, these diagnostic tests should be routinely included in the evaluation of athletes with complex VAs. A risk score including the results of these tests can greatly help in the prediction of concealed structural heart diseases’ diagnosis. More than 2/3 of subjects were judged eligible to participate in sports at 6 months’ follow-up. Abstract Figure 1. ROC curves for diagnosis

To provide a brief overview of some relevant technological advances in the field of three-dimensional electroanatomical mapping (3D-EAM) that have recently entered the clinical arena and their role in guiding catheter ablation (CA) of complex atrial and ventricular arrhythmias. In this technical report, we describe the general features of three novel algorithms featured in the updated CARTO PRIME™ mapping module for CARTO®3 version 7 3D-EAM system (Biosense Webster Inc., Diamond Bar, CA, USA): local activation time (LAT) hybrid, coherent mapping and map replay modules. We also report three challenging arrhythmia cases in which CA was successfully guided by these softwares. The LAT hybrid module was used in a case of premature ventricular complex originating from the right coronary cusp. This algorithm facilitated safe positioning of the ablation catheter away from the right coronary ostium, avoiding potential harm to this vital structure. The coherent mapping module helped to identify the critical as well as a bystander isthmus of an atrial macro-re-entrant tachycardia in a grown-up patient with congenital heart disease. The map replay module allowed rapid retrospective activation mapping of two unstable ventricular tachycardias in a case of nonischemic cocaine-associated cardiomyopathy. 3D-EAM systems offer significant advantages in the management of challenging arrhythmias, and the introduction of novel algorithms underpins improvements in patients’ outcomes. Given the increasing sophistication of these systems, however, a close collaboration among cardiac electrophysiologists, engineers and technicians is highly needed in order to get the best from the available technology.

Aims Recently, voltage gradient mapping of Koch's triangle to find low-voltage connections, or 'voltage bridges', corresponding to the anatomic position of the slow pathway, has been introduced as a method to ablate atrioventricular nodal reentry tachycardia (AVNRT) in children. Thus, we aimed to assess the effectiveness of voltage mapping of Koch's triangle, combined with the search for the slow potential signal in 'low-voltage bridges', to guide cryoablation of AVNRT in children. Methods and results From June 2015 to May 2016, 35 consecutive paediatric patients (mean age 12.1 ± 4.5 years) underwent 3D-guided cryoablation of AVNRT at our Institution. Fifteen children were enrolled as control group (mean age 14 ± 4 years). A voltage gradient mapping of Koch's triangle was obtained in all patients, showing low-voltage connections in all children with AVNRT but not in controls. Prior to performing cryoablation, we looked for the typical 'hump and spike' electrogram, generally considered to be representative of slow pathway potential within a low-voltage bridge. In all patients the 'hump and spike' electrogram was found inside bridges of low voltage. Focal or high-density linear lesions, extended or not, were delivered guided by low-voltage bridge visualization. Acute success rate was 100%, and no recurrence was reported at a mean follow-up of 8 ± 3 months. Conclusions Voltage gradient mapping of Koch's triangle, combined with the search for the slow potential signal in low-voltage bridges, is effective in guiding cryoablation of AVNRT in paediatric patients, with a complete acute success rate and no AVNRT recurrences at mid-term follow-up.

Background Transcatheter cryoablation is a well-established technique for the treatment of atrioventricular nodal reentry tachycardia (AVNRT) in children. Nevertheless, atrioventricular nodal slow-pathway conduction may recur after an acutely successful procedure. The aim of this study was to evaluate the long-term outcome of acutely successful AVNRT cryoablations in pediatric patients in case of focal cryolesion and in case of need for High-Density Linear Lesion (HDLL) cryoablation due to focal failure. Methods Sixty-nine consecutive pediatric patients (30 males, mean age 12.4 ± 3.2 years; range: 5.4-18.0 years) underwent 3D-guided cryoablation for AVNRT at our institution from July 2013 to November 2014. When a focal cryoablation was acutely unsuccessful, a 3D-guided HDLL was created delivering multiple overlapping cryolesions/cryoenergy applications from the ventricular side of the tricuspid annulus to the atrial side, including the site of focal cryoablation if transiently successful. Results No permanent cryoablation-related complications occurred. Acute success rate was 98.5% (68 out of 69): in 55.9% (38 out of 68) with focal-lesion and in 44.1% (30 out of 68) with HDLL. Mean follow-up was 25.3 months and AVNRT recurrence rate was 13.2% (nine out of 68): 5.2% (two out of 38) with focal lesion and 23.3% (seven out of 30) with HDLL (P = 0.036). Conclusions In cryoablation of AVNRT in children, the need for a more aggressive protocol (HDLL), due to the failure of focal ablation, is strictly related to higher recurrence rates. Indeed, AVNRT recurrences after cryoablation in children seem to be due to a larger and deeper substrate rather than due to the type of energy used.

BACKGROUND SonR sensor signal correlates well with myocardial contractility expressed in terms of left ventricular (LV) dP/dt max. The aim of our study was to evaluate the changes in myocardial contractility during isometric effort in heart failure patients undergoing cardiac resynchronization therapy (CRT) with right atrial SonR sensor. METHODS Thirty-one patients (19 men, 65 ± 7 years, LV ejection fraction [LVEF] 28% ± 5%, in sinus rhythm) were implanted with a CRT-defibrillator (CRT-D) device equipped with SonR sensor, which was programmed in VVI mode at 40 beats/min. Twenty-four hours after implantation, each patient underwent a noninvasive hemodynamic evaluation at rest and during isometric effort, including: (1) measurement of beat-to-beat endocavitary SonR signal; (2) echocardiographic assessment; and (3) continuous measurement of blood pressure with Nexfin method (BMEYE, Amsterdam, the Netherlands). The following contractility parameters were considered: (1) mean value of beat-to-beat SonR signal; (2) mean value of LV dP/dt by Nexfin system; and (3) fractional shortening (FS) by echocardiography. RESULTS At the third minute of the isometric effort, mean value of SonR signal significantly increased from baseline (P < 0.001). Similarly, mean value of both LV dP/dt by Nexfin and FS significantly increased compared to the resting condition (P < 0.001; P < 0.001). While in 27 (88%) patients SonR signal increased at the third minute of the isometric effort, in four (12%) patients SonR signal decreased. In these patients, both LV dP/dt by Nexfin and FS consensually decreased. CONCLUSIONS In CRT patients, SonR sensor is able to detect changes in myocardial contractility in a consensual way like noninvasive methods such as Nexfin system and echocardiography.

Background Cardiac resynchronization therapy (CRT) nonresponse remains a major clinical problem. Autoantibodies specific for the β1-adrenergic (β1-AAbs) and muscarinic (M2-AAbs) receptors are found in patients with chronic heart failure (HF) of various etiologies. Materials and Methods We retrospectively analyzed 73 HF patients (median age 67 years, 84% males, New York Heart Association II–IV, in sinus rhythm, left ventricular ejection fraction 15% in left ventricular end-systolic volume at 6 months follow-up). Renal function (RF) parameters (creatinine [Cr], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR Modified Diet in Renal Disease], cystatin C [Cys-C], and neutrophil gelatinase-associated lipocalin [NGAL]) were also evaluated. Results A significantly higher percentage of patients positive for β1-AAbs (OD sample/OD reference ratio >2.1) in nonresponders than in responder patients was observed (57% vs 27%, P = 0.004). No influence of M2-AAbs on CRT-D response was demonstrated. β1-AAbs were predictive of a poor CRT-D response (odds ratio [OR] [95% confidence interval (CI)] 3.64 [1.49–8.88], P = 0.005), also after adjustment for RF parameters (OR [95% CI] 4.95 [1.51–16.26], P = 0.008) observed to influence CRT-D response (Cr P = 0.03, BUN P = 0.009, Cys-C P = 0.02). The positive rates of β1-AABs in patients with abnormal blood level of Cr, eGFR, Cys-C, and NGAL were significantly higher than those with normal levels (P = 0.03, P = 0.02, P = 0.001, P = 0.007, respectively). Conclusions Our study suggests that (1) the evaluation of β1-AAb is useful to identify responders to CRT-D; (2) the presence of β1-AAbs is in relationship with elevated renal function parameters.

Background— The gut-derived hormone ghrelin, especially its acylated form, plays a major role in the regulation of systemic metabolism and exerts also relevant cardioprotective effects; hence, it has been proposed for the treatment of heart failure (HF). We tested the hypothesis that ghrelin can directly modulate cardiac energy substrate metabolism. Methods and Results— We used chronically instrumented dogs, 8 with pacing-induced HF and 6 normal controls. Human des-acyl ghrelin [1.2 nmol/kg per hour] was infused intravenously for 15 minutes, followed by washout (rebaseline) and infusion of acyl ghrelin at the same dose. 3 H-oleate and 14 C-glucose were coinfused and arterial and coronary sinus blood sampled to measure cardiac free fatty acid and glucose oxidation and lactate uptake. As expected, cardiac substrate metabolism was profoundly altered in HF because baseline oxidation levels of free fatty acids and glucose were, respectively, >70% lower and >160% higher compared with control. Neither des-acyl ghrelin nor acyl ghrelin significantly affected function and metabolism in normal hearts. However, in HF, des-acyl and acyl ghrelin enhanced myocardial oxygen consumption by 10.2±3.5% and 9.9±3.7%, respectively ( P P Conclusions— Acute increases in des-acyl or acyl ghrelin do not interfere with cardiac metabolism in normal dogs, whereas they enhance free fatty acid oxidation and reduce glucose oxidation in HF dogs, thus partially correcting metabolic alterations in HF. This novel mechanism might contribute to the cardioprotective effects of ghrelin in HF.

Background Previous studies have reported that the left ventricular (LV) pacing site is a major determinant of the hemodynamic response to cardiac resynchronization therapy (CRT). However, lead positioning in a lateral or posterolateral cardiac vein may not be optimal for every patient. The objective of this study was to assess the relationship between the right ventricular (RV)-to-LV conduction time and the systolic function during CRT on the basis of changes to LV pressure-volume loops. Methods Left ventricular pressure and volume data were determined using a conductance catheter during CRT device implantation in 10 patients. Four endocardial LV sites were systematically assessed at four atrioventricular delays. The RV-to-LV conduction time was measured as the time interval between spontaneous peak R waves, recorded through the RV lead and the LV catheter. Results The optimal pacing site varied among patients. However, the pacing site associated with the maximum RV-to-LV conduction time resulted in a stroke volume improvement comparable to the pacing site identified through individual hemodynamic optimization (41 ± 17 mL vs 44 ± 18 mL, P = 0.266). Moreover, the RV-to-LV conduction time recorded at each endocardial pacing site correlated positively with the increase in stroke volume (r = 0.537; P < 0.001), stroke work (r = 0.642; P < 0.001), and the pressure-derivative maximum (r = 0.646; P < 0.001) obtained with CRT. Conclusions An optimal acute response to CRT can be obtained by positioning the LV lead at the site associated with the maximum RV-to-LV conduction time. A significant correlation appears to exist between RV-to-LV conduction time and the improvement in systolic function with CRT.

Aims The haemodynamic SonR sensor is able to measure myocardial contractility. The isometric effort is useful in quantifying left ventricular (LV) performance. We investigated the amplitude changes in SonR signal over time and during static exercise according to the recovery of the left ventricle. Methods and results Twenty five patients [18 male, 70 ± 8 years, LV ejection fraction (LVEF) 29 ± 5%, in sinus rhythm] underwent biventricular SonR implantable cardioverter defibrillator implant. After procedure and at 6 months, each patient underwent detection of SonR signal and continuous measurement of blood pressure, at rest and during isometric effort. During evaluation at baseline device was programmed in VVI at 40 bpm while in DDD at 60 bpm at follow-up. At 6 months, LV reverse remodelling was investigated. Cardiac resynchronization therapy patients were considered responders when an absolute improvement in LV ejection fraction ≥ 5% occurred. At 6 months, 14 (56%) patients were responders and 11 (44%) non-responders (mean LVEF 40 ± 10% vs. 27 ± 6%, respectively). In responders, SonR value did not significantly change at follow-up compared to baseline ( P = 0.894). At follow-up, SonR value was not significantly different between two groups ( P = 0.651). SonR signal significantly increased during isometric effort in responders ( P = 0.002) while it slightly decreased in non-responders at follow-up ( P = 0.572). No differences were observed in response to isometric effort between two groups at baseline ( P = 0.182, P = 0.069, respectively). Conclusions The absolute SonR amplitude provides limited information on the status of LV performance. The variation in SonR signal during static exercise is more likely to identify responders at follow-up.

Introduction Advances in 3D electroanatomic-mapping technologies have resulted in a safe and effective profile of radiofrequency (RF) catheter ablation. The aim of this study was to evaluate a different catheter ablation approach in patients with left-sided accessory pathways (APs). Methods and results From January 2015 to December 2015, 30 patients (median age 11 years, median weight 45 kg) with manifest or concealed left-sided APs underwent RF catheter ablation with a new protocol. All procedures were performed with the CARTO UNIVU™ system, integrating electroanatomic maps with fluoroscopic views. A 7 Fr ablation catheter was inserted into the right femoral vein and advanced into the right atrium. Geometrical reconstruction and activation map of the right atrium, tricuspid annulus, and coronary sinus were acquired. The ablation catheter was then inserted into the left femoral artery and advanced through the aorta and aortic valve, creating an activation map of the mitral annulus. Catheter ablation was targeted to the site of the earliest activation. No complications occurred. The median procedure and fluoroscopy times were 130 min and 6 s, with a median fluoroscopy dose 0.5 mGy. An average of two catheters was used. Long-term success rate was 97% (29/30) at a median follow-up of 9.6 months. This approach reduced fluoroscopy time, dose and number of catheters used compared with manifest or concealed left-sided AP ablation using CARTO 3™ (P < 0.05). Conclusions This new ablation protocol seems to be promising in reducing fluoroscopy exposure and number of catheters used during left-sided AP ablation in children.

In 1628, William Harvey described the importance of the auricle during the motion of the heart: “First the auricle contracts, and this force the abundant blood it contains as the cistern and reservoir of the veins, into the ventricle. This being filled, the heart raises itself, makes its fibers tense, contracts, and beats. By this beat it at once ejects into the arteries the blood received from the auricle.” Three centuries later, Gesell described the association between atrial fibrillation and a drop in the arterial pressure, further describing that the blood pressure effects were reversed with restoration of sinus rhythm [1] (Fig. 2.1).

Luigi Padeletti1, Giosuè Mascioli2, Alessandro Paoletti Perini1, Gino Grifoni1, Laura Perrotta1, Procolo Marchese3, Luca Bontempi3, Antonio Curnis31Istituto di Clinica Medica e Cardiologia, Università degli Studi di Firenze, Italia; 2Elettrofisiologia, Istituto Humanitas Gavazzeni, Bergamo, Italia; 3Elettrofisiologia, Spedali Civili, Brescia, ItaliaAbstract: Population aging and broader indications for the implant of cardiac implantable electronic devices (CIEDs) are the main reasons for the continuous increase in the use of pacemakers (PMs), implantable cardioverter-defibrillators (ICDs) and devices for cardiac resynchronization therapy (CRT-P, CRT-D). The growing burden of comorbidities in CIED patients, the greater complexity of the devices, and the increased duration of procedures have led to an augmented risk of infections, which is out of proportion to the increase in implantation rate. CIED infections are an ominous condition, which often implies the necessity of hospitalization and carries an augmented risk of in-hospital death. Their clinical presentation may be either at pocket or at endocardial level, but they can also manifest themselves with lone bacteremia. The management of these infections requires the complete removal of the device and subsequent, specific, antibiotic therapy. CIED failures are monitored by competent public authorities, that require physicians to alert them to any failures, and that suggest the opportune strategies for their management. Although the replacement of all potentially affected devices is often suggested, common practice indicates the replacement of only a minority of devices, as close follow-up of the patients involved may be a safer strategy. Implantation of a PM or an ICD may cause problems in the patients' psychosocial adaptation and quality of life, and may contribute to the development of affective disorders. Clinicians are usually unaware of the psychosocial impact of implanted PMs and ICDs. The main difference between PM and ICD patients is the latter's dramatic experience of receiving a shock. Technological improvements and new clinical evidences may help reduce the total burden of shocks. A specific supporting team, providing psychosocial help, may contribute to improving patient quality of life.Keywords: pacemaker, cardiac cardioverter-defibrillator, cardiac implantable electronic devices, infection, recall, quality of life&nbsp

Background During radiofrequency ablation, effective contact is crucial in determining lesions efficacy. Objective The purpose of this study was to compare operators' ability to assess contact pressure using visual and tactile feedbacks together or alone in an experimental model. Methods In a in vitro experimental setup replicating manual catheter manipulation and recording the applied force, evaluators were asked to identify three levels of force (first, ablation, and maximum contact) as the catheter contacted the tissue model using (1) visual feedback only by fluoroscopy, "blinded" to touch; (2) tactile feedback only, blinded to fluoroscopy; and (3) both tactile and visual feedback together. The latter was regarded as reference. The experiment was repeated using a catheter force sensing technology during robotic navigation. Results During manual navigation, tighter association was shown for the visual method than for the tactile method: median difference with reference: first contact –1 ( P = .97) vs –2 ( P = .90); ablation contact 2 ( P = .1) vs –7 ( P = .03); maximum contact 2 ( P = .06) vs –28 ( P = .02). Bland-Altman plot and Deming regression confirmed for the visual method the good agreement with reference and the absence of bias at any level and showed for the tactile higher values and proportional bias that reached statistical significance at ablation and maximum contact. During robotic navigation, agreement was higher for the tactile than for the visual only method. Conclusion During manual navigation, visual feedback alone is in better agreement with the reference compared to the tactile only approach. During robotic navigation, agreement is looser for the visual only approach. More objective feedback of contact pressure during ablation procedures is desirable.

Background— During cardiac resynchronization therapy (CRT) device implantation, the pacing lead is usually positioned in the coronary sinus (CS) to stimulate the left ventricular (LV) epicardium. Transvenous LV endocardial pacing via transseptal puncture has been proposed as an alternative method. In the present study, we evaluated the acute hemodynamic effects of CRT through LV endocardial pacing in heart failure patients by analyzing LV pressure–volume relationships. Methods and Results— LV pressure and volume data were determined via conductance catheter during CRT device implantation in 10 patients. In addition to the standard epicardial CS pacing, the following endocardial LV sites were systematically assessed: the site transmural to the CS lead, the LV apex, the septal midwall, the basal lateral free wall, and the midlateral free wall. Four atrioventricular delays were tested. There was a significant improvement of systolic function with CRT in all LV pacing configurations, whereas no differences in systolic or diastolic function were detected between LV epicardial and endocardial transmural sites. The optimal pacing site varied among patients but was rarely related to relatively longer activation delays, as assessed by analyzing endocardial electric activation maps. Nonetheless, positioning the pacing lead at the optimal endocardial LV site in each patient significantly improved LV performance in comparison with conventional CS site stimulation (stroke volume, 83 [79–112] mL versus 73 [62–89] mL; P =0.034). Conclusions— Pacing at the optimal individual LV endocardial site yields enhanced LV performance in comparison with conventional CS site stimulation. Endocardial LV pacing might constitute an alternative approach to CRT, when CS pacing is not viable.