Roberto De Ponti

Atrial tachycardias in patients with congenital heart disease: a minimally invasive simplified approach in the use of three-dimensional electroanatomic mapping.

AIMSnAtrial tachycardia (AT) is a common complication after repair of congenital heart disease (CHD). This two-centre prospective study evaluated the ability of three-dimensional electroanatomic mapping (EAM) to guide ablation of ATs in this particular population with a minimally invasive simplified approach.nnnMETHODS AND RESULTSnThirty-one consecutive patients (mean age 26 ± 17 years) with AT after repair of CHD were treated with a very limited number of intracavitary catheters and a specific setting of the Window of Interest (WoI) for the ablation of post-surgical ATs. A single-intracavitary catheter approach was performed in 22 patients, whereas an overall use of two intracavitary catheters in the other nine patients. Thirty-one patients exhibited 41 ATs. Seventy-six per cent of these were macro-reentrant ATs (MRATs), and 24% were focal ATs (FAT). The mid-diastolic isthmus (MDI) was located in the right atrial free wall (RAFW) in 82.8% of MRATs. Also in FATs, the RAFW was the most common site (77.8%) of the ectopic focus. Fifty-eight per cent of MRATs showed a double-loop reentry, with both loops sharing the same MDI in all cases. In 87% of cases, the abolition of the MRAT was obtained by applying radiofrequency energy to the MDI. Ninety per cent of FATs were successfully ablated. Mean conduction velocity and voltage amplitude had significantly lower values in successfully treated than in unsuccessfully treated MRATs.nnnCONCLUSIONnThree-dimensional EAM, performed with a minimally invasive simplified approach and by using a specific parameter setting of the WoI, showed to be very effective to guide ablation of ATs in CHD patients.

Transient atriovenous reconnection induced by adenosine after successful pulmonary vein isolation with the cryothermal energy balloon

AIMSnCryothermal energy balloon ablation (CBA), using cryogenic ablative energy, has proven very effective in producing pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). Adenosine testing after PV isolation has demonstrated to be able to unmask incomplete lesion after radiofrequency (RF) ablation. The aim of our study was to assess the rate of transient atriovenous reconnection induced by adenosine after successful PV isolation with the CBA in a group of patients with paroxysmal AF.nnnMETHODS AND RESULTSnWe prospectively enrolled 39 patients (31 male; age 59 +/- 11 years) elected to circumferential PV isolation with CBA for highly symptomatic paroxysmal AF. A total of 149 PVs were evidenced. Adenosine testing after CBA induced a left atrium-PV reconnection only in 7 (4.6%) of PV.nnnCONCLUSIONnOur study showed a low rate of transient PV reconnection after adenosine infusion following successful PV isolation with CBA. However, larger studies will be needed in order to confirm our findings and the prognostic value of adenosine testing after successful PV isolation obtained with CBA.

Iterative atrial tachycardia originating from the coronary sinus musculature.

Coronary Sinus Atrial Tachycardia. A case of iterative atrial tachycardia leading to dilated cardiomyopathy is reported. During electrophysiologic study, the tachycardia showed a markedly irregular cycle length associated with changes in atrial activation breakthrough as demonstrated by coronary sinus (CS) recordings and frequently degenerated into self‐terminating atrial fibrillation. Left atrial transseptal mapping demonstrated the earliest endocardial atrial activation close to the posterolateral mitral annulus, but this was invariably later than that recorded within the CS, where low‐energy radiofrequency applications eliminated the tachycardia. No acute vessel damage was observed at postablation CS angiography. In accordance with previously published experimental data, we hypothesized that the muscular sleeves surrounding the CS might be involved in the genesis of this tachycardia. During 6‐month follow‐up, the patient remained asymptomatic without tachycardia recurrences and with complete recovery of left ventricular function, confirming the reversible nature of the tachycardia‐induced cardiomyopathy.

Prospective European Survey on Atrial Fibrillation Ablation: Clinical Characteristics of Patients and Ablation Strategies Used in Different Countries

Atrial fibrillation (AF) ablation is widely adopted. Our aim was to conduct a prospective multicenter survey to verify patients’ characteristics, approaches, and technologies adopted across Europe.

Risk–Benefit Profile of Direct-Acting Oral Anticoagulants in Established Therapeutic Indications: An Overview of Systematic Reviews and Observational Studies

Since 2008, the direct-acting oral anticoagulants (DOACs) have expanded the therapeutic options of cardiovascular diseases with recognized clinical and epidemiological impact, such as non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE), and also in the preventive setting of orthopedic surgical patients. The large body of evidence, not only from pivotal clinical trials but also from ‘real-world’ postmarketing observational findings (e.g. analytical epidemiological studies and registry data) gathered to date allow for a first attempt at verifying a posteriori whether or not the pharmacological advantages of the DOACs actually translate into therapeutic innovation, with relevant implications for clinicians, regulators and patients. This review aims to synthesize the risk–benefit profile of DOACs in the aforementioned consolidated indications through an ‘evidence summary’ approach gathering the existent evidence-based data, particularly systematic reviews with meta-analyses of randomized controlled trials, as well as observational studies, comparing DOACs with vitamin K antagonists. Clinical evidence will be discussed and compared with major international guidelines to identify whether an update is needed. Controversial clinically relevant safety issues will be also examined in order to highlight current challenges and unsettled questions (e.g. actual bleeding risk in susceptible populations). It is anticipated that the large number of publications on NVAF or VTE (44 systematic reviews with meta-analyses and 12 observational studies retained in our analysis) suggests the potential existence of overlapping studies and calls for common criteria to qualitatively and quantitatively assess discordances, thus guiding future research.

Adverse events associated with the use of direct-acting oral anticoagulants in clinical practice: Beyond bleeding complications

Non-vitamin K oral anticoagulants, also known as direct oral anticoagulants (DOACs), have entered thexa0market in 2008 with the expected breakthrough potential of circumventing limitations related to treatmentxa0with vitamin K antagonists (eg, warfarin) by virtue of their pharmacological properties. Although dataxa0derived from premarketing randomized clinical trials have largely demonstrated the clinical benefit ofxa0DOACs, especially in terms of reduced risk of intracranial bleeding, it is important to monitor the safetyxa0in the postmarketing phase, which better reflects real-world patients with comorbidities and polypharmacotherapy,xa0in order to assess the actual risk-benefit profile. In this critical review, we aimed to evaluatexa0the evidence on the latest debated safety issues. In the first section, we will discuss: 1) the need forxa0pharmacovigilance (ie, the science and activities relating to the detection, assessment, understanding,xa0and prevention of adverse effects or any other drug-related problems in the real-world setting), and 2) thexa0importance of properly interpreting postmarketing data to avoid unnecessary alarm. In the second section,xa0emerging and debated safety issues potentially associated with the use of DOACs in the postmarketingxa0setting will be assessed: 1) the potential coronary risk (which emerged during the preapproval period);xa02) the occurrence of liver injury (a risk undetected in clinical trials and highlighted by case reports orxa0series); and 3) the potential for renal damage (a still unclear safety issue). It is anticipated that hepaticxa0and renal issues still require dedicated postauthorization safety studies to ultimately assess causality.

Emerging therapeutic uses of direct-acting oral anticoagulants: An evidence-based perspective

&NA; Direct‐acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short‐ and long‐term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre‐approval pivotal trials to real‐world post‐marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin‐K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non‐valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk‐benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin‐induced thrombocytopenia, anti‐phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories. Graphical abstract Figure. No caption available.

Left atrial appendage thrombi relate to easily accessible clinical parameters in patients undergoing atrial fibrillation transcatheter ablation: A multicenter study

BACKGROUNDnTransesophageal echocardiography (TEE) is routinely performed before atrial fibrillation (AF) transcatheter ablation to exclude the presence of left atrial (LA) or LA appendage (LAA) thrombi. The aim of the study is to evaluate if easily accessible clinical parameters may relate to the presence of LA or LAA thrombi to identify patients who could potentially avoid TEE.nnnMETHODS AND RESULTSnBetween January 2012 and September 2014, data from 1539 consecutive patients undergoing TEE, as a work-up before AF transcatheter ablation, in six large volume centers were collected. Baseline clinical features, CHA2DS2-VASc score, transthoracic echocardiography and presence of thrombi at TEE were recorded. Exclusion criteria were valvular, hypertrophic or dilated cardiomyopathy, previous heart surgery or an ejection fraction ≤35%. Mean age was 59.6±10.4years, 1215 (78.9%) were males; 951 (62.9%) presented in sinus rhythm (SR) on admission, 324 (21.1%) had undergone at least one previous ablation and 900 (58.5%) had CHA2DS2-VASc score 0-1. Thrombi were encountered in 12 patients (0.8%). SR at TEE independently related to the absence of thrombi (OR 5.15, 95% CI 1.38-19.02, p=0.015); in addition to this, no patient with a CHA2DS2-VASc score 0-1 and SR on admission presented thrombi at TEE (specificity 100%, p=0.011).nnnCONCLUSIONnIn a selected population of patients referred for AF ablation, LA/LAA thrombi prevalence is low. No patients in SR with CHA2DS2-VASc score 0-1 presented LAA thrombi at TEE, identifying a significant subset of patients who could potentially safely be spared from pre-procedural TEE.

Perioperative Safety and Efficacy of Different Anticoagulation Strategies With Direct Oral Anticoagulants in Pulmonary Vein Isolation: A Meta-Analysis

OBJECTIVESnThe purpose of this study was to evaluate the safety and efficacy of uninterrupted and interrupted direct oral anticoagulant (DOAC) administration in patients undergoing pulmonary vein isolation (PVI).nnnBACKGROUNDnThe optimal periprocedural management of DOACs in patients undergoing PVI is not well defined, and different strategies are used.nnnMETHODSnA systematic search of PubMed/MEDLINE, Ovid/MEDLINE, and EMBASE was performed. Three strategies for periprocedural DOAC administration were considered: uninterrupted, mildly interrupted (<12 h), and interrupted (≥12 h). Primary endpoints were major bleeding (MB) and thromboembolic (TE) complications; pooled weighted mean incidence (WMI) was calculated using a random-effects model. A secondary endpoint was the WMI of overall bleeding (OB).nnnRESULTSnThe analysis included 43 studies for a total of 8,362 patients. DOACs showed similar safety and efficacy in the 3 subgroups. The WMI of MB was 1.02%, 1.49%, and 1.17% for the uninterrupted, mildly interrupted, and interrupted strategy, respectively; the WMI of TE complications was 0.16%, 0.46%, and 0.49% for the uninterrupted, mildly interrupted, and interrupted strategy, respectively, with no heterogeneity. OB appeared to be higher in uninterrupted (6.33%) and mildly interrupted (8.62%) groups compared with the interrupted (3.53%), with substantial heterogeneity among studies. No interaction was found between the incidence of MB and TE complications and different DOACs.nnnCONCLUSIONSnIn patients undergoing PVI, these 3 anticoagulation strategies may have similar safety and efficacy in terms of MB and TE complications. OB appears to be higher in uninterrupted and mildly interrupted strategies compared with the interrupted strategy. No substantial differences were observed among DOACs regarding the incidence of MB and TE complications.

Evolving cardiovascular uses of direct-acting oral anticoagulants: a paradigm shift on the horizon?

Direct-acting oral anticoagulants (DOACs), by virtue of pharmacological properties perceived as innovative, are changing the therapeutic scenario of patients requiring short- and long-term anticoagulation. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirms that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy, effectiveness and unequivocally documents a clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (AF) and venous thromboembolism. The following issues are attracting considerable clinical interest: (a) identifying specific subpopulations of patients with AF most likely to benefit from one of these agents (the so-called tailored therapy), and (b) expanding therapeutic indications in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk–benefit profile of DOACs, as compared to VKAs or heparins, is still incompletely characterized. In cardiology, the challenging task of selecting a suitable or even the most appropriate DOAC for patients with AF and a particular phenotype prompted experts to provide suggestions based on careful review of subgroups of patients from pivotal RCTs. However, in the past few months, variegated multicenter trials have been published (RE-CIRCUIT, PIONEER-AF-PCI, GEMINI-ACS-1), with potential influence on clinical practice. Therefore, this review aims to update the latest evidence on the evolving therapeutic uses of DOACs in the cardiovascular area, addressing potential impact for clinicians.