PREventive left atrial appenDage resection for the predICtion of fuTure atrial fibrillation: design of the PREDICT AF study Background Atrial fibrillation is the most common cardiac arrhythmia, posing a heavy burden on patients’ wellbeing and healthcare budgets. Patients undergoing cardiac surgery are at risk of developing postoperative atrial fibrillation (POAF), new-onset atrial fibrillation and subsequent atrial fibrillation-related complications, including stroke. Sufficient clinical identification of patients at risk fails while the pathological substrate changes that precede atrial fibrillation remain unknown. Here, we describe the PREDICT AF study design, which will be the first study to associate tissue pathophysiology and blood biomarkers with clinical profiling and follow-up of cardiothoracic surgery patients for the prediction of future atrial fibrillation. Methods PREDICT AF will include 150 patients without atrial fibrillation and a CHA2DS2–VASc score of at least 2 undergoing cardiac surgery. The left atrial appendage will be excised during surgery and blood samples will be collected before surgery and at 6 and 12 months’ follow-up. Tissue and blood analysis will be used for the discovery of biomarkers including microRNAs and protein biomarkers. The primary study endpoint is atrial fibrillation, which will be objectified by 24 h Holters and ECGs after 30 days for POAF and after 6, 12 and 24 months for new-onset atrial fibrillation. Secondary endpoints include the dynamic changes of blood biomarkers over time and other atrial arrhythmias. PREDICT AF participants may benefit from extensive postoperative care with clinical phenotyping, rhythm monitoring and primary prevention of stroke. Conclusion We here describe the PREDICT AF trial design, which will enable the discovery of biomarkers that truly predict POAF and new-onset atrial fibrillation by combining tissue and plasma-derived biomarkers with comprehensive clinical follow-up data. Trial registration Retrospectively registered NCT03130985 27 April 2017. Correspondence to Joris R. de Groot, MD, PhD, FESC, Department of Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands Tel: +31 (020) 5664503; e-mail: j.r.degroot@amsterdamumc.nl Received 16 April, 2019 Revised 8 August, 2019 Accepted 22 August, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jcardiovascularmedicine.com). © 2019 Italian Federation of Cardiology. All rights reserved.

Platelet-to-lymphocyte ratio at the time of carotid endarterectomy is associated with acute coronary syndrome occurrence Aims Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are used in the clinical management of patients at cardiovascular (CV) risk. In this pilot study, we aimed at evaluating the predictive role of NLR and PLR toward the occurrence of acute coronary syndrome (ACS) across an 18-month follow-up period. Correlations involving NLR and PLR with regard to circulating and intraplaque biomarkers have been investigated, too. Methods 196 patients with severe carotid artery stenosis undergoing carotid endarterectomy (CEA) were enrolled at IRCCS Ospedale Policlinico San Martino (Genoa, Italy) from 2008 to 2011. Clinical information and blood samples were collected the day before CEA and patients were clinically followed up for 18 months. Results NLR positively correlated with fibrinogen and intraplaque M1 macrophages. PLR positively correlated with fibrinogen and inversely with triglycerides and CCL5. By a ROC curve analysis, PLR, but not NLR, has been found to predict ACS at 18-month follow-up (cutoff > 153.6). Kaplan-Meier analysis demonstrated that patients above the PLR cut-off experienced higher rates of ACS at 18 months. Cox proportional hazard regression analysis confirmed these results irrespective of potential confounders, such as previous coronary artery disease and CV preventive therapy. Conclusion PLR is a good predictor of ACS occurrence and a quick, inexpensive, and easy-to-use tool to better assess the CV risk in patients at high risk, such as those with severe carotid atherosclerosis. Correspondence to Aldo Bonaventura, MD, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, viale Benedetto XV 6, 16132 Genoa, Italy E-mail: aldo.bonaventura@edu.unige.it; aldo.bonaventura@vcuhealth.org Received 14 May, 2019 Revised 9 August, 2019 Accepted 23 August, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jcardiovascularmedicine.com). © 2019 Italian Federation of Cardiology. All rights reserved.

Neuro-arrhythmology: a challenging field of action and research: a review from the Task Force of Neuro-arrhythmology of Italian Association of Arrhythmias and Cardiac Pacing There is a growing interest in the study of the mechanisms of heart and brain interactions with the aim to improve the management of high-impact cardiac rhythm disorders, first of all atrial fibrillation. However, there are several topics to which the scientific interests of cardiologists and neurologists converge constituting the basis for enhancing the development of neuro-arrhythmology. This multidisciplinary field should cover a wide spectrum of diseases, even beyond the classical framework corresponding to stroke and atrial fibrillation and include the complex issues of seizures as well as loss of consciousness and syncope. The implications of a more focused interaction between neurologists and cardiologists in the field of neuro-arrhythmology should include in perspective the institution of research networks specifically devoted to investigate ‘from bench to bedside’ the complex pathophysiological links of the abovementioned diseases, with involvement of scientists in the field of biochemistry, genetics, molecular medicine, physiology, pathology and bioengineering. An investment in the field could have important implications in the perspectives of a more personalized approach to patients and diseases, in the context of ‘precision’medicine. Large datasets and electronic medical records, with the approach typical of ‘big data’ could enhance the possibility of new findings with potentially important clinical implications. Finally, the interaction between neurologists and cardiologists involved in arrythmia management should have some organizational implications, with new models of healthcare delivery based on multidisciplinary assistance, similarly to that applied in the case of syncope units. Correspondence to Giuseppe Boriani, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena University Hospital, Modena, Italy E-mail: giuseppe.boriani@unimore.it Received 28 March, 2019 Revised 9 July, 2019 Accepted 16 August, 2019 © 2019 Italian Federation of Cardiology. All rights reserved.

An unusual case of iatrogenic Twiddler's syndrome Twiddler's syndrome is an uncommon cause of cardiac implantable electronic device malfunction, usually due to manipulation of the pulse generator. A few spontaneous cases have already been described. We present the unique case of a 77-year-old woman who experienced iatrogenic Twiddler's syndrome. Correspondence to Aurora Sanniti, MD, Electrophysiology and Pacing Unit, Humanitas Mater Domini Clinical Institute, Via Gerenzano, 2, 21053 Castellanza (VA), ItalyTel: +39 0331 476267; fax: +39 0331 476201; E-mail: aurora.sanniti@libero.it Received 6 April, 2019 Revised 23 July, 2019 Accepted 8 August, 2019 © 2019 Italian Federation of Cardiology. All rights reserved.

A 10-year follow-up of a patient affected by myotonic dystrophy type 1 with implantable cardioverter–defibrillator implanted for secondary prevention Cardiac involvement in myotonic dystrophy type 1 (DM1) is frequent with an increased incidence of conduction disturbances and sudden cardiac death when compared with the general population. We described the case of a young man in whom the diagnosis of DM1 was made 8 years after the occurrence of cardiac arrest (CA) owing to ventricular fibrillation and ICD was implanted 4 years later (12 years after CA). During the subsequent 10 years, despite the deterioration of neuromuscular conditions, no appropriate or inappropriate shocks occurred. Correspondence to Luigi De Ambroggi, MD, NEMO Clinical Center - Neurorehabilitation Unit, University of Milan, Piazza Ospedale Maggiore 3, 20162 Milan, Italy E-mail: luigi.deambroggi@unimi.it Received 15 April, 2019 Revised 22 June, 2019 Accepted 22 July, 2019 © 2019 Italian Federation of Cardiology. All rights reserved.

Looking for the right way: right coronary artery originating from a left anterior descending acutely occluded just distally to the bifurcation We describe the case of a patient referred to our cathlab due to anterior ST segment elevation myocardial infarction. Through the right radial artery route, after multiple attempts to cannulate the right coronary artery (RCA), we proceeded to left coronary angiography, which showed an abnormal origin of RCA from the middle segment of the left anterior descending (LAD), that was occluded just distally to the bifurcation. We performed a primary angioplasty of the LAD throughout a direct stent implantation, with a good angiographical result and the evidence of a myocardial bridging below the implanted stent. The patient was discharged, asymptomatic, after 7 days. Correspondence to Marco Di Maio, MD, Department of Cardiology, University of Campania Luigi Vanvitelli, Naples, Italy Tel: +39 3454489003; e-mail: marcodimaio88@gmail.com Received 7 January, 2019 Revised 10 February, 2019 Accepted 4 May, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jcardiovascularmedicine.com). © 2019 Italian Federation of Cardiology. All rights reserved.

Mechanical atrial recovery after cardioversion in persistent atrial fibrillation evaluated by bidimensional speckle tracking echocardiography Background Atrial fibrillation induces reversible electrical and mechanical modifications (atrial remodeling). Atrial stunning is a mechanical dysfunction with preserved bioelectrical function, occurring after successful atrial fibrillation electrical cardioversion (ECV). Two-dimensional speckle tracking echocardiography is a new technology for evaluating atrial mechanical function. We assessed atrial mechanical function after ECV with serial two-dimensional speckle tracking echocardiography evaluations. The investigated outcome was left atrium mechanical recovery within 3 months. Methods A total of 36 patients [mean age 73 (7.9) years, 23 males] with persistent atrial fibrillation underwent conventional transthoracic and transesophageal echocardiography before ECV. Positive global atrial strain (GSA+) was assessed at 3 h, 1, 2, 3, 4 weeks and 3 months after ECV. Mechanical recovery was defined as the achievement of a GSA+ value of 21%. Results Independent predictors of GSA+ immediately after ECV (basal GSA+) were E/e′ ratio and left atrial appendage anterograde flow velocity. During the follow-up, 25% of patients suffered atrial fibrillation recurrence. In 12/36 patients (33%) left atrium mechanical recovery was detected (mechanical recovery group), while in 15/36 (42%) recovery did not occur (no atrial mechanical recovery group). At univariate analysis, the variables associated with recovery, were basal GSA+ (P = 0.015) and maximal velocity left atrial appendage (P = 0.022). Female sex (P = 0.038), N-terminal pro-B type natriuretic peptide (P = 0.013), E/e′ (P = 0.042) and the indexed left atrium volume (P = 0.019) were associated with the lack of left atrium mechanical recovery. Conclusion In almost half of the patients, the left atrium did not resume mechanical activity within the 3 months after ECV, despite sinus rhythm recovery. The left atrium of these patients was larger, stiffer and their E/E′ was higher, suggesting a higher endocavitary pressure compared with mechanical recovery patients. These findings might suggest an increased thromboembolic risk. Correspondence to Antonio Vincenti, MD, FESC, Ospedale San Giuseppe Multimedica IRCCS, Via San Vittore 12, 20123 Milano, Italy Tel: +00 39 330237357; e-mail: antonio.vincenti@multimedica.it Received 22 May, 2019 Revised 8 August, 2019 Accepted 8 August, 2019 © 2019 Italian Federation of Cardiology. All rights reserved.

Diagnostic ‘nightmares’ in an HIV patient with a cardiac mass and a previous history of tuberculosis No abstract available

When the bundle skips a beat… Intermittent bundle branch block is generally a functional phenomenon because of heart rate variation. It commonly depends by a dependent tachycardia or bradycardia bundle branch block. A rare alternative cause is the Wenckebach phenomenon in bundle branch. We show a singular case of concealed 3:2 Wenckebach phenomenon in the right bundle branch. Correspondence to Carmelo Buttà, MD, Cardiology Unit, Department of Clinical and Experimental Medicine, University of Messina, via Consolare Valeria, 98124 Messina, Italy Tel: +390902212341; fax: +390902212087; e-mail: carmelob147@tiscali.it Received 9 June, 2019 Revised 5 August, 2019 Accepted 8 August, 2019 © 2019 Italian Federation of Cardiology. All rights reserved.

In heart failure with reduced ejection fraction patients’ left ventricular global longitudinal strain is enhanced after 1-year therapy with sacubitril/valsartan compared with conventional therapy with angiotensin-converting enzyme-inhibitors or AT1 blockers: results from a retrospective cohort study No abstract available