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BACKGROUND Sex-related electrocardiographic differences are a well-known phenomenon, but not their expression in patients with atrial fibrillation (AF). In this study we aim to assess the presence of significant sex-related differences in ECG features, with particular attention to P-wave parameters, of a large cohort of patients affected by different types of AF. METHODS A 5-min resting 16-lead ECG was evaluated for 1119 AF patients in sinus rhythm. The durations of the main ECG waves and intervals were measured for both atrial and ventricular activity. Moreover, the beat-to-beat P-wave variability was computed for lead II and for the first principal component (PC1) computed across the 16 leads. The percentage of variance explained by PC1 was computed. RESULTS Males compared to females showed significantly longer RR interval (1.02 ± 0.16 s vs 0.97 ± 0.15 s, p

Backgrounds: Data on optimal antiplatelet therapy in patients undergoing stenting of the proximal left anterior descending artery (LAD) are limited. Methods: This is a post-hoc analysis of the GLOBAL LEADERS trial, a prospective, multi-center, randomized controlled trial, comparing the experimental strategy (1-month dual anti-platelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) with the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in relation to stenting of the proximal LAD. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction (MI) and key secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at two years. Results: Among 15,845 patients included in the analysis, 3823 (23.9%) patients underwent stenting of the proximal LAD, while 12,022 (75.2%) did not. In the proximal LAD stenting group, there was no significant difference in the risk of the primary endpoint between the two antiplatelet strategies (3.38% vs. 3.93%; hazard ratio [HR]:0.86; 95% CI:0.62–1.20; Pinteraction = 0.951). However, the risk of any MI (2.63% vs. 3.88%; HR:0.68; 95% CI:0.47–0.97; Pinteraction = 0.015) and any revascularization (7.84% vs. 9.94%; HR:0.78; 95% CI:0.63–0.97; Pinteraction = 0.058) was significantly lower in the experimental strategy group, while demonstrating a similar risk of BARC type 3 or 5 bleeding between the two antiplatelet strategies (1.93% vs. 1.99%; HR:0.98; 95% CI:0.62–1.54; Pinteraction = 0.981). Conclusions: The present study showed patients having stenting to the proximal LAD could potentially benefit from the experimental strategy with lower ischaemic events without a trade-off in major bleeding at two years.

Background: Left bundle branch block (LBBB) morphology is associated with improved outcome of cardiac resynchronisation therapy (CRT) and is an important criterion for patient selection. There are, however, multiple definitions for LBBB. Moreover, applying these definitions seems subjective. We investigated the inter- and intraobserver agreement in the determination of LBBB using available definitions, and clinicians' judgement of LBBB.Methods: Observers were provided with 12-lead ECGs of 100 randomly selected CRT patients. Four observers judged the ECGs based on different LBBB-definitions (ESC, AHA/ACC/HRS, MADIT, and Strauss). Additionally, four implanting cardiologists scored the same 100 ECGs based on their clinical judgement. Observer agreement was summarized through the proportion of agreement (P) and kappa coefficient (k).Results: Relative intra-observer agreement using different LBBB definitions, and within clinical judgement was moderate (range k 0.47-0.74 and k = 0.76 (0.14), respectively). The inter-observer agreement between observers using LBBB definitions as well as between clinical observers was minimal to weak (range k 0.19-0.44 and k = 0.35 (0.20), respectively). The probability of classifying an ECG as LBBB by available definitions varied considerably (range 0.20-0.76). The agreement between different definitions of LBBB ranged from good (P = 0.95 (0.07)) to weak (P = 0.40 (0.22)). Furthermore, correlation between the different LBBB definitions and clinical judgement was poor (range phi 0.30-0.55).Conclusion: Significant variation in the probability of classifying LBBB is present in using different definitions and clinical judgement. Considerable intra-and inter-observer variability adds to this variation. Interdefinition agreement varies significantly and correlation of clinical judgement with LBBB classification by definitions is modest at best. (C) 2019 Elsevier B.V. All rights reserved.

BACKGROUND: Unrecognized incomplete pulmonary vein isolation (PVI), as opposed to post-PVI pulmonary vein reconnection, may be responsible for clinical recurrences of atrial fibrillation (AF). To date, no data are available on the use of high-resolution mapping (HRM) during cryoballoon (CB) ablation for AF as the index procedure. The aims of this study were: - to assess the value of using a HRM system during CB ablation procedures in terms of ability in acutely detecting incomplete CB lesions; - to compare the 8-pole circular mapping catheter (CMC, Achieve) and the 64-pole mini-basket catheter (Orion) with respect to pulmonary vein (PV) signals detection at baseline and after CB ablation; - to characterize the extension of the lesion produced by CB ablation by means of high-density voltage mapping. METHODS: Consecutive patients with drug-resistant paroxysmal or early-persistent AF undergoing CB ablation as the index procedure, assisted by a HRM system, were retrospectively included in this study. RESULTS: Atotal of 33 patients (25 males; mean age: 59 ± 18 years, 28 paroxysmal AF) were included. At baseline, CMC catheter revealed PV activity in 102 PVs (77%), while the Orion documented PV signals in all veins (100%). Failure of complete CB-PVI was more frequently revealed by atrial re-mapping with the Orion as compared to the Achieve catheter (24% vs 0%, p 0.5 mV. A total of 29 patients (88%) remained free of symptomatic AF during a mean follow-up of 13.2 ± 3.7 months. CONCLUSION: Atrial re-mapping after CB ablation by means of a HRM system improves the detection of areas of incomplete ablation, characterizes the extension of the cryo-ablated tissue and can identify abolishment of potential non-PVI related sources of AF.

Background Remote monitoring (RM) technology embedded in cardiac rhythm devices permits continuous monitoring of device function, and recording of selected cardiac physiological parameters and cardiac arrhythmias and may be of utmost utility during Coronavirus (COVID-19) pandemic, when in-person office visit for regular follow-up were postponed. However, patients not alredy followed-up via RM represent a challenging group of patients to be managed during the lockdown. Methods We reviewed patient files scheduled for an outpatient visit between January 1, 2020 and May 11th, 2020 to assess the proportion of patients in whom RM activation was possible without office visit, and compared them to those scheduled for visit before the lockdown. Results During COVID-19 pandemic, RM activation was feasible in a minority of patients (7.8% of patients) expected at outpatient clinic for a follow-up visit and device check-up. This was possible in a good proportion of complex implantable devices such as cardiac resynchronization therapy and implantable cardioverter defibrillator but only in 3 patients with a pacemaker the RM function could be activated during the period of restricted access to hospital. Conclusions Our experience strongly suggest to consider the systematic activation of RM function at the time of implantation or – by default programming - in all cardiac rhythm management devices., Highlights • Remote Monitoring is associated with improved survival • patients not followed-up via RM represent a challenging group of patients to be managed, specially during pandemic • Our experience strongly suggest to consider the systematic activation of RM function at the time of implantation or – by default programming - in all cardiac rhythm management devices

Background We sought to assess and compare the prediction power of the PRECISE-DAPT and PARIS risk scores with regards to bleeding events in elderly patients suffering from acute coronary syndromes (ACS) and undergoing invasive management. Methods Our external validation cohort included 1883 patients older >74 years admitted for ACS and treated with PCI from 3 prospective, multicenter trials. Results After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3–5 bleedings (p = 0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (p = 0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all χ2 > 0.05), but PARIS risk score was associated to a greater overestimation of the risk (p = 0.02). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%. Conclusions In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance.

Background\ud Risk factors for further bleeding and ischemic events after acute coronary syndrome (ACS) often overlap. Little is known about sex-based differences in the management and outcomes of ACS patients according to their combined bleeding-ischemic risk.\ud \ud Methods\ud All ACS hospitalizations in the United Kingdom (2010-2017) were retrospectively analyzed, stratified by sex and bleeding-ischemic risk combination (using CRUSADE and GRACE scores). Multivariable logistic regression was performed to examine association between risk-groups and 1) receipt of guideline-recommended management and 2) in-hospital outcomes.\ud \ud Results\ud Of 584,360 patients, a third of males (32.3%) and females (32.6%) were in the dual high-risk group (High CRUSADE- High GRACE). In comparison to the dual low-risk group (Low CRUSADE-Low GRACE), the dual high-risk patients of both sexes were 59-83% less likely to receive coronary angiography (CA) or percutaneous coronary intervention (PCI), 31-34% less likely to receive dual antiplatelet therapy (DAPT) on discharge, with a significant increase in odds of MACE (8-fold), all-cause and cardiac mortality (30 to 40-fold), and bleeding (40-43%). The greatest difference in management and clinical outcomes between sexes was found in the dual-high risk group where females were less likely to receive guideline-recommended therapy (PCI and DAPT), compared to males, and were more likely to experience MACE, all-cause and cardiac mortality.\ud \ud Conclusion\ud ACS patients with dual high-risk for bleeding and recurrent ischemia, especially females, are less likely to receive guideline-recommended therapy and experience significantly worse outcomes. Novel strategies are needed to effectively manage this highly prevalent, complex patient group and address the under-treatment of females.

Background: CRT has been proven to achieve most benefit in patients with left bundle branch block morphology (LBBB). However, ECG criteria to define LBBB significantly differ from each other. Objective of the study was to evaluate the impact of different ECG criteria for LBBB definition on survival, hospitalization for heart failure and reverse remodelling in patients who received cardiac resynchronization therapy (CRT). Methods and results: Three-hundred-sixteen consecutive patients were included in the analysis. Six different classifications were assessed in baseline ECGs of patients who received a CRT device: a QRS duration of >= 150 ms and LBBB according to AHA/ACC/HRS, ESC 2006, ESC 2009, ESC 2013 and the classification proposed by Strauss and colleagues. In univariate analysis, the ESC 2009 and 2013 and the Strauss classifications were significantly associated with a reduction in cumulative probability for heart failure (HF) andmortality (HR 0.60, 95% CI 0.42-0.86, HR 0.61, 95% CI 0.43-0.87 and HR 0.57, 95% CI 0.40-0.80, respectively). Inmultivariate analysis, the association with the combined endpoint was confirmed only for ESC 2009 and 2013 classifications and for Strauss. Moreover, the cumulative probability of all-cause death and HF hospitalizations was higher in patients who were negative for all the 5 LBBB classifications. Conclusions: This study shows that the strength of the association of LBBB to outcome in CRT depends on the ECG classifications used to define LBBB, the simplest criteria (ESC 2009 and 2013) providing the best association with clinical endpoints in CRT. (c) 2018 Elsevier B.V. All rights reserved.

Acute coronary syndrome (ACS)-related morbidity and mortality remain substantial. Data on temporal trends in in-hospital complications of ACS patients are scarce. This study sought to investigate whether the incidence of in-hospital complications of ACS patients changed over time.Acute coronary syndrome patients prospectively enrolled in the National Registry of Acute Myocardial Infarction in Switzerland (AMIS Plus) between 2003 and 2018 and with available data on in-hospital complications were included in the analysis. Rates of in-hospital complications, including recurrent angina, recurrent myocardial infarction, cerebrovascular events, cardiogenic shock, bleeding, acute renal failure, sepsis/systemic inflammatory response syndrome (SIRS)/multiorgan dysfunction syndrome (MODS), AV block needing pacing and new-onset atrial fibrillation, were assessed for each 2-year period.Among 47,845 ACS patients, in-hospital complications significantly decreased from 22.0% in 2003/2004 to 18.9% in 2017/2018 (p for trend0.001). An initial decline in rates of in-hospital complications to 15.7% in 2009/2010 (p for trend0.001) was followed by a constant increase thereafter (p for trend = 0.002). While rates of recurrent angina, recurrent myocardial infarction, and cardiogenic shock decreased over time, rates of bleeding events, acute renal failure, sepsis/SIRS/MODS, and new-onset atrial fibrillation increased. Rates of in-hospital complications were higher in women, mainly due to a constantly increased risk of bleeding and AV block needing pacing.The decrease in ischemic complications was paralleled by a concomitant increase in non-ischemic events. These findings emphasize that advanced strategies targeting non-ischemic complications are warranted to further improve quality of care of ACS patients.

Objectives: The electrocardiogram (ECG) of patients with BrS in sinus rhythm might reflect intrinsic atrial electrical abnormalities independent from any previous atrial fibrillation (AF). Aim of this study is to investigate the presence of P-wave abnormalities in patients with BrS and no history of AF, and to compare them with those displayed by patients with documented paroxysmal AF and by healthy subjects. Methods: Continuous 5-min 16-lead ECG recordings in sinus rhythm were obtained from 72 participants: 32 patients with a type 1 Brugada ECG, 20 patients with a history of paroxysmal AF and 20 age-matched healthy subjects. Different ECG-based features were computed on the P-wave first principal component representing the predominant morphology across leads and containing the maximal information on atrial depolarization: duration, full width half maximum (FWHM), area under the curve and number of peaks in the wave. Results: Patients with BrS and no history of AF (mean age: 53 +/- 12 years; males: 28 pts., spontaneous type 1 ECG: 20 pts., SCN5A mutation: 10 pts) presented with longer P-wave duration, higher FWHM and wider area under the curve in comparison with the other two groups. Although P-wave features were abnormal in BrS patients, no significant difference was found between patients with spontaneous type 1 ECG and ajmaline-induced type 1 ECG, symptomatic and asymptomatic ones, and between patients with a pathogenic SCNA5 mutation and patients without a known gene mutation. Conclusions: Patients with BrS without previous occurrence of AF present with a concealed abnormal atrial phenotype. In these patients atrial electrical abnormalities can be detected even in the absence of an overt ECG ventricular phenotype, symptoms and a SCN5A mutation. (c) 2017 Elsevier B.V. All rights reserved.

Several studies suggested beneficial effects of perioperative levosimendan on postoperative outcome after cardiac surgery. However, three large randomized controlled trials (RCTs) have been recently published and presented neutral results. We performed a systematic review with meta-analysis and trial sequential analysis (TSA) to assess benefits and harms of perioperative levosimendan therapy in cardiac surgery.Electronic databases were searched up to September 2017 for RCTs on preoperative levosimendan versus any type of control. The Cochrane methodology was employed. We calculated odds ratio (OR) or Risk Ratio (OR) and 95% confidence interval (CI) using fixed-effects meta-analyses and we further performed TSA.We included data from 40 RCTs and 4246 patients. Pooled analysis of 5 low risk of bias trials (1910 patients) showed no association between levosimendan and mortality (OR 0.86 [95% CI, 0.62, 1.18], p=0.34, TSA inconclusive), acute kidney injury, need of renal replacement therapy, myocardial infarction, ventricular arrhythmias, and serious adverse events, but an association with higher incidence of supraventricular arrhythmias (RR 1.11 [95% CI, 1.00, 1.24], p=0.05, TSA inconclusive) and hypotension (RR 1.15 [95% CI, 1.01, 1.30], p=0.04, TSA inconclusive). Analysis including all 40 trials found that levosimendan was associated with lower postoperative mortality (OR 0.56 [95% CI, 0.44, 0.71], p0.00001, TSA conclusive), acute kidney injury, and renal replacement therapy, and higher incidence of hypotension.There is not enough high-quality evidence to neither support nor discourage the systematic use of levosimendan in cardiac surgery.

Background The European Association of Cardiology (ESC) Guidelines on the diagnosis and treatment of acute heart failure (AHF) indicate prompt therapy initiation and performance of relevant investigations as paramount. Specifically, echocardiography prior to treatment is advocated only with hemodynamic instability, and the evaluation of clinical signs of peripheral perfusion and congestion is suggested as guidance for early interventions. Given the growing body of evidence on the diagnostic/monitoring capabilities of bedside ultrasound (including focused cardiac ultrasound, comprehensive echocardiography, lung ultrasound), we discuss the potential benefit of an integrated clinical/ultrasound approach at the very early stages of acute heart failure. Methods and Results We proposed a narrative review of the current evidence on the clinical-ultrasound integrated approach to AHF, with special emphasis on the components of the early diagnostic-therapeutic workup where cardiac, inferior vena cava and lung ultrasound showed high diagnostic accuracy and the capability of substantially changing an exclusively clinically-oriented patient management. A proactive comment to the ESC guidelines is made, suggesting an integration of clinical and biochemical assessment, as defined by guidelines, with combined bedside ultrasound on may help in the definition of AHF pathophysiology and treatment. Conclusion A multi-organ integrated clinical-ultrasound approach should be advocated as part of the clinical-diagnostic workup at AHF very early phase. Whenever competence and technology available, bedside ultrasound, along with clinical and biochemical assessment, should target AHF profiling, identify the cause of AHF, and subsequently aid disease course and response to treatment monitoring.

Background: Both duration and morphology of the T-wave are regarded important parameters describing repolarization of the ventricles. Conventionally, T-wave concordance is explained by an inverse relation between the time of depolarization (TD) and repolarization (TR). Little is known about T-wave morphology and TD-TR relations in patients with heart failure.Methods: Electro-anatomic maps were obtained in the left (LV) and right ventricle (RV) and in the coronary sinus (CS) in patients with heart failure with narrow (nQRS, n = 8) and wide QRS complex with (LBBB, n = 15) and without left bundle branch block (non-LBBB, n = 7). TD and TR were determined from the thus acquired electrograms.Results: In nQRS and non-LBBB patients, TD-TR relations had a slope between 0 and +1, indicating that repolarization followed the sequence of depolarization. In LBBB patients, repolarization occurred significantly earlier in the RV than in the LV, fitting with the idea that the discordant T-waves in LBBB are secondary to the abnormal depolarization sequence. However, the slopes of the TD-TR relations in the LV and CS were not significantly different from zero, indicating no major spatial gradient in LV repolarization, despite a considerable gradient in depolarization. Remarkable was also the large (similar to 100ms) transseptal gradient in repolarization. Values of the slopes of the TD-TR relation overlapped between the three patient groups, despite a difference in T-wave morphology between LBBB (all discordant) and nQRS patients (all flat/biphasic).Conclusions: Discordant T-waves in LBBB patients are explained by interventricular dispersion in repolarization. T-wave morphology is determined by more factors than the TD-TR relation alone. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

Background To investigate the performance of the MI Sxscore in a multicentre randomised trial of patients undergoing primary percutaneous coronary intervention (PPCI). Methods and results The MI Sxscore was prospectively determined among 1132 STEMI patients enrolled into the COMFORTABLE AMI trial, which randomised patients to treatment with bare-metal (BMS) or biolimus-eluting (BES) stents. Patient- (death, myocardial infarction, any revascularisation) and device-oriented (cardiac death, target-vessel MI, target lesion revascularisation) major adverse cardiac events (MACEs) were compared across MI Sxscore tertiles and according to stent type. The median MI SXscore was 14 (IQR: 9–21). Patients were divided into tertiles of Sxscorelow (≤ 10), Sxscoreintermediate (11–18) and Sxscorehigh (≥ 19). At 1 year, patient-oriented MACE occurred in 15% of the Sxscorehigh, 9% of the Sxscoreintermediate and 5% of the Sxscorelow tertiles (p < 0.001), whereas device-oriented MACE occurred in 8% of the Sxscorehigh, 6% of the Sxscoreintermediate and 4% of the Sxscorelow tertiles (p = 0.03). Addition of the MI Sxscore to the TIMI risk score improved prediction of patient- (c-statistic value increase from 0.63 to 0.69) and device-oriented MACEs (c-statistic value increase from 0.65 to 0.70). Differences in the risk for device-oriented MACE between BMS and BES were evident among Sxscorehigh (13% vs. 4% HR 0.33 (0.15–0.74), p = 0.007 rather than those in Sxscorelow: 4% vs. 3% HR 0.68 (0.24–1.97), p = 0.48) tertiles. Conclusions The MI Sxscore allows risk stratification of patient- and device-oriented MACEs among patients undergoing PPCI. The addition of the MI Sxscore to the TIMI risk score is of incremental prognostic value among patients undergoing PPCI for treatment of STEMI.

Background Despite several clinical studies, efficacy of coronary artery bypass grafting (CABG) surgery versus percutaneous coronary intervention (PCI) in patients with left main (LM) disease remains controversial. The objective of this meta-analysis of randomized trials was to evaluate the clinical outcome of CABG versus PCI with drug-eluting stents in LM coronary disease. Methods We systematically searched online databases up to March 2017 for randomized trials comparing CABG to PCI with drug-eluting stents. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results We included data from 5 randomized trials and 4595 patients. At 30days, CABG was associated with higher stroke (OR 2.54 [95% CI, 1.02–6.31]) and periprocedural myocardial infarction (OR 1.45 [95% CI, 1.00–2.10]), with no other significant differences compared to PCI. At 1year, CABG reduced repeat revascularization (OR 0.56 [95% CI, 0.40–0.77]), but increased stroke (OR 5.11 [95% CI, 1.62–16.12]). At 3–5years, CABG reduced repeat revascularization (OR 0.55 [95% CI, 0.45–0.67]) and non-periprocedural myocardial infarction (OR 0.45 [95% CI, 0.29–0.70]), without significant differences on other outcomes. Conclusions From the present updated meta-analysis of available studies on LM coronary disease treatment, there were no differences in mortality, myocardial infarction, and stroke rate at 3–5years follow-up after CABG or PCI, but CABG decreased the rate of repeat revascularization and non-periprocedural infarction. However, at short-term follow-up, CABG showed higher rate of stroke and periprocedural myocardial infarction, but these effects attenuated over time. These findings merit further investigation at longer follow-up.

The aim of this study was to determine overall and aetiology-related incidence of secondary prevention ICD implantation over the last 15years in Canton Ticino and to assess clinical outcome according to time period of implantation.Consecutive patients treated by implantation of an ICD for secondary prevention from 2000 to 2015 were included in the current study and compared between 5-year cohorts (2000/2004; 2005/2009; 2010/2015). Yearly implantation rate, changing in clinical presentation over years and events during follow-up were evaluated. One-hundred fifty six patients were included. ICD implantation rate increased from 2.1 in 2000-2005 to 5.1 in 2010-2015, respectively (p 0.001). There was an increase in the proportion of non-ischaemic patients and of ventricular tachycardia (VT) as presenting rhythm. No differences in appropriate ICD interventions were observed according to aetiology, presenting arrhythmia or type of device. Reverse remodelling was observed more often in non-ischaemic patients, without any influence on the occurrence of appropriate interventions. Previous myocardial infarction (MI), atrial fibrillation (AF), NYHA class 2-3 and left ventricular ejection fraction (LVEF)35% were predictors of appropriate therapies during follow-up.Rate of implants for secondary prevention indication has almost doubled during the last 15years. Importantly, there has been a progressive increase of non-ischaemic patients receiving an ICD, and of VT as presenting rhythm. Patients had an overall good survival and a relatively low incidence of appropriate therapies. Improvement of ejection fraction did not correlate with risk reduction of ventricular arrhythmias.