Publications by authors named "Carmen Adduci"

28 Publications

  • Page 1 of 1

Left Ventricular Remodeling in Hypertrophic Cardiomyopathy: An Overview of Current Knowledge.

J Clin Med 2021 Apr 7;10(8). Epub 2021 Apr 7.

Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy.

While most patients with hypertrophic cardiomyopathy (HCM) show a relatively stable morphologic and clinical phenotype, in some others, progressive changes in the left ventricular (LV) wall thickness, cavity size, and function, defined, overall, as "LV remodeling", may occur. The interplay of multiple pathophysiologic mechanisms, from genetic background to myocardial ischemia and fibrosis, is implicated in this process. Different patterns of LV remodeling have been recognized and are associated with a specific impact on the clinical course and management of the disease. These findings underline the need for and the importance of serial multimodal clinical and instrumental evaluations to identify and further characterize the LV remodeling phenomenon. A more complete definition of the stages of the disease may present a chance to improve the management of HCM patients.
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http://dx.doi.org/10.3390/jcm10081547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067545PMC
April 2021

Home delivery of the communicator for remote monitoring of cardiac implantable devices: a multicenter experience during the COVID-19 lockdown.

Pacing Clin Electrophysiol 2021 Apr 27. Epub 2021 Apr 27.

Department of Cardiovascular, Respiratory, Nephrology, Anaesthesiology and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.

Background: During the COVID-19 pandemic in-person visits for patients with cardiac implantable electronic devices should be replaced by remote monitoring (RM), in order to prevent viral transmission. A direct home-delivery service of the RM communicator has been implemented at 49 Italian arrhythmia centers.

Methods: According to individual patient preference or the organizational decision of the center, patients were assigned to the home-delivery group or the standard in-clinic delivery group. In the former case, patients received telephone training on the activation process and use of the communicator. In June 2020, the centers were asked to reply to an ad hoc questionnaire to describe and evaluate their experience in the previous three months.

Results: RM was activated in 1324 patients: 821 (62%) received the communicator at home and the communicator was activated remotely. Activation required one additional call in 49% of cases, and the median time needed to complete the activation process was 15 minutes [25 -75 percentile: 10-20]. 753 (92%) patients were able to complete the correct activation of the system. At the time when the questionnaire was completed, 743 (90%) communicators were regularly transmitting data. The service was generally deemed useful (96% of respondents) in facilitating the activation of RM during the COVID-19 pandemic and possibly beyond.

Conclusions: Home delivery of the communicator proved to be a successful approach to system activation, and received positive feedback from clinicians. The increased use of a RM protocol will reduce risks for both providers and patients, while maintaining high-quality care. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/pace.14251DOI Listing
April 2021

Multi-Modality Imaging Approach in a Challenging Case of Surgically Corrected Partial Anomalous Pulmonary Venous Return and Atrial Tachycardia Treated With Radiofrequency Ablation.

Cureus 2021 Jan 30;13(1):e13009. Epub 2021 Jan 30.

Radiology, Sant'Andrea Hospital - Sapienza University of Rome, Roma, ITA.

Pulmonary anomalous venous return (PAPVR) is defined as a congenital anomaly in which at least one but not all of the pulmonary veins abnormally drain into a systemic vein or directly into the right atrium. Signs and symptoms related to this condition are due to the hemodynamic abnormalities secondary to left-to-right shunt and the possible presence of other associated cardiac anomalies (e.g., sinus venous atrial septal defect). Therefore, depending on the extent of the shunt, the clinical presentation of PAPVR is variable, ranging from asymptomatic patients to patients affected by severe heart failure with right-sided volume overload. PAPVR with a clinically significant shunt should be referred for surgical correction with different techniques depending on the presence of associated cardiac anomalies. We are presenting a case of partial anomalous venous return (PAPVR) in a 66-year-old man who underwent surgery 26 years ago to correct an anomalous venous connection between the right superior pulmonary vein (RSPV) and the superior vena cava (SVC) through a veno-atrial baffle. The patient was admitted to the emergency department due to atrial tachycardia. Trans-thoracic echocardiography (TTE) showed a dilated right ventricle (RV) with mild RV systolic dysfunction and pulmonary hypertension. Cardiac magnetic resonance (CMR) further confirmed the findings described by TTE and also demonstrated areas of fibrosis replacement in the hinge points. Cardiac computed tomography (CCT) was able to accurately depict and evaluate the surgically created veno-atrial baffle and also showed an anomalous connection between the left superior pulmonary vein (LSPV) and the brachiocephalic vein (BCV) through a vertical vein. The patient was successfully treated with radiofrequency ablation for his arrhythmia.
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http://dx.doi.org/10.7759/cureus.13009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920218PMC
January 2021

Implantation technique and optimal subcutaneous defibrillator chest position: a PRAETORIAN score-based study.

Europace 2020 12;22(12):1822-1829

Department of Experimental, Diagnostic and Specialty Medicine, Institute of Cardiology, University of Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy.

Aims: The traditional technique for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation involves three incisions and a subcutaneous pocket. Recently, a two-incision and intermuscular (IM) technique has been adopted. The PRAETORIAN score is a chest radiograph-based tool that predicts S-ICD conversion testing. We assessed whether the S-ICD implantation technique affects optimal position of the defibrillation system according to the PRAETORIAN score.

Methods And Results: We analysed consecutive patients undergoing S-ICD implantation. The χ2 test and regression analysis were used to determine the association between the PRAETORIAN score and implantation technique. Two hundred and thirteen patients were enrolled. The S-ICD generator was positioned in an IM pocket in 174 patients (81.7%) and the two-incision approach was adopted in 199 (93.4%). According to the PRAETORIAN score, the risk of conversion failure was classified as low in 198 patients (93.0%), intermediate in 13 (6.1%), and high in 2 (0.9%). Patients undergoing the two-incision and IM technique were more likely to have a low (<90) PRAETORIAN score than those undergoing the three-incision and subcutaneous technique (two-incision: 94.0% vs. three-incision: 78.6%; P = 0.004 and IM: 96.0% vs. subcutaneous: 79.5%; P = 0.001). Intermuscular plus two-incision technique was associated with a low-risk PRAETORIAN score (hazard ratio 3.76; 95% confidence interval 1.01-14.02; P = 0.04). Shock impedance was lower in PRAETORIAN low-risk patients than in intermediate-/high-risk categories (66 vs. 96 Ohm; P = 0.001). The PRAETORIAN score did not predict shock failure at 65 J.

Conclusion: In this cohort of S-ICD recipients, combining the two-incision technique and IM generator implantation yielded the lowest PRAETORIAN score values, indicating optimal defibrillation system position.

Clinical Trial Registration: http://clinicaltrials.gov/ Identifier: NCT02275637.
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http://dx.doi.org/10.1093/europace/euaa231DOI Listing
December 2020

Prevention of Sudden Cardiac Death: Focus on the Subcutaneous Implantable Cardioverter-Defibrillator.

High Blood Press Cardiovasc Prev 2020 Aug 9;27(4):291-297. Epub 2020 Jun 9.

Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035, 00189, Rome, Italy.

The implantable cardioverter-defibrillator (ICD) is the most effective therapy to prevent sudden cardiac death (SCD) in high-risk patients. To overcome infections and failure of transvenous leads, the most frightening complications of conventional ICDs, a completely subcutaneous ICD (S-ICD) has been developed and is currently adopted in routine clinical practice. In view of their long life-expectancy, low competitive risk of dying from non-arrhythmic causes, and high lifetime risk of lead-related complications requiring surgical revisions, young patients with cardiomyopathies and inherited arrhythmia syndromes have traditionally been considered ideal candidates for the S-ICD. However, as growing evidence supported S-ICD safety and efficacy, initial niche implant indications were abandoned in favor of a widespread use of this technology, that is currently adopted in common ICD candidates with severe left ventricular dysfunction. Indeed, guidelines recommend S-ICD implantation as an alternative to TV-ICDs in all ICD candidates, unless pacing is required. This review focuses on the contemporary experience with the S-ICD and explores future scenarios in which device-to-device communication will enable to combine leadless therapies.
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http://dx.doi.org/10.1007/s40292-020-00394-xDOI Listing
August 2020

Assessing Atrial Fibrillation Substrates by P Wave Analysis: A Comprehensive Review.

High Blood Press Cardiovasc Prev 2020 Oct 25;27(5):341-347. Epub 2020 May 25.

Division of Cardiology, Department of Clinical and Molecular Medicine, Sapienza University, Rome, Via di Grottarossa 1035, 00189, Rome, Italy.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Pharmacologic and non-pharmacologic rhythm control strategies impact on AF-related symptoms, while leaving largely unaffected the risk of stroke. Moreover, up to 20% of AF patients are asymptomatic during paroxysmal relapses of arrhythmia, thus underlying the need for early markers to identify at-risk patients and prevent cerebrovascular accidents. Indeed, non-invasive assessment of pre-clinical substrate changes that predispose to AF could provide early identification of at-risk patients and allow for tailored care paths. ECG-derived P wave analysis is a simple-to-use and inexpensive tool that has been successfully employed to detect AF-associated structural and functional atrial changes. Beyond standard electrocardiographic techniques, high resolution signal averaged electrocardiography (SAECG), by recording microvolt amplitude atrial signals, allows more accurate analysis of the P wave and possibly AF risk stratification. This review focuses on the evidence that support P wave analysis to assess AF substrates, predict arrhythmia relapses and guide rhythm-control interventions.
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http://dx.doi.org/10.1007/s40292-020-00390-1DOI Listing
October 2020

Prognostic implications of nonsustained ventricular tachycardia morphology in high-risk patients with hypertrophic cardiomyopathy.

J Cardiovasc Electrophysiol 2020 08 9;31(8):2093-2098. Epub 2020 Jun 9.

Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Introduction: The prognostic impact of nonsustained ventricular tachycardia (NSVT) morphology has never been explored in hypertrophic cardiomyopathy (HCM). In a single-center cohort of consecutive HCM patients implanted with an implanted cardioverter-defibrillator (ICD), we assessed NSVT morphology patterns and their prognostic implications.

Methods: A cohort of consecutive HCM patients implanted with an ICD was followed from ICD implantation to last follow-up visit. Patients were assessed for NSVT as stored events in ICD memory. Ventricular tachycardias (VTs) were classified as monomorphic (MM) or polymorphic according to intracardiac electrogram morphology.

Results: One hundred nine consecutive HCM patients (68 males; mean age: 45 ± 17 years) composed the study population. During follow-up (71 ± 48 months), 7 polymorphic NSVT in 4 patients and 370 MM NSVT in 42 patients were retrieved from ICD memory. Among patients with only MM NSVT, 19 (45%) had one morphology, 17 (41%) had two morphologies, 3 (7%) had three morphologies, and 3 (7%) had four morphologies. Patients with polymorphic NSVT had the highest risk of ICD interventions (HR, 5.04; 95% CI, 1.26-20.19; P = .02). A stepwise increase of the risk of ICD interventions in patients with two, three, and four NSVT morphologies was observed. Out of 16 patients with both NSVT and ICD-treated VTs, 13 (81%) had at least one ICD-treated VT with the same morphology of a previous long-lasting NSVT.

Conclusions: In high-risk HCM patients, the occurrence of polymorphic NSVT and of NSVT with multiple morphologies carries a high risk for ICD interventions. Sustained VTs tend to recur with the same morphology of previous long-lasting NSVTs.
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http://dx.doi.org/10.1111/jce.14571DOI Listing
August 2020

Ventricular fibrillation undersensing due to air entrapment in a patient implanted with a subcutaneous cardioverter defibrillator.

J Cardiovasc Electrophysiol 2019 Aug 20;30(8):1373-1374. Epub 2019 Jun 20.

Division of Cardiology, Department of Clinical and Molecular Medicine, St Andrea Hospital, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.1111/jce.14005DOI Listing
August 2019

The subcutaneous implantable cardioverter-defibrillator: Current trends in clinical practice between guidelines and technology progress.

Eur J Intern Med 2019 Jul 17;65:6-11. Epub 2019 Apr 17.

Arrhythmia & EP Research Center, IRCCS Humanitas Research & University Hospital, Rozzano, Milan, Italy.

The subcutaneous implantable cardioverter defibrillator (S-ICD) is a valuable alternative to the conventional trans-venous ICD (TV-ICD) for the prevention of sudden cardiac death (SCD). Prospective registries showed that the S-ICD is safe and effective in treating ventricular tachyarrhythmias in high-risk patients without pacing indications. While in earlier studies patients implanted with S-ICDs were young and mostly affected by channelopathies, contemporary S-ICD cohorts include patients with severely impaired left ventricular function and significant comorbidities. This review focuses on S-ICD evidence-based use and highlights current gaps between guidelines recommendations and real-world clinical practice.
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http://dx.doi.org/10.1016/j.ejim.2019.04.003DOI Listing
July 2019

Safety and efficacy of anti-tachycardia pacing in patients with hypertrophic cardiomyopathy implanted with an ICD.

Pacing Clin Electrophysiol 2019 06 5;42(6):610-616. Epub 2019 Apr 5.

Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Background: In hypertrophic cardiomyopathy (HCM) patients implanted with an implantable cardioverter defibrillator (ICD), clinical outcomes of antitachycardia pacing (ATP) have been poorly explored. In a retrospective analysis of a cohort of consecutive HCM patients implanted with an ICD, we aimed to assess the efficacy, safety, and clinical value of ATP.

Methods: The cohort of HCM patients implanted with a transvenous ICD and followed in our center was assessed for device intervention from implantation to last clinical follow-up.

Results: Overall 77 patients (45 males; mean age: 46 ± 16 years) were analyzed. After 67 ± 41 months, 24 patients had 49 ventricular tachycardia/fibrillation (VT/VF) appropriately treated (5.8% per year). Among 39 monomorphic VTs, ATP was effective in 27 (success rate: 69%). Mean time from VT onset to ATP delivery was 9.1 ± 4.9 s. The only clinical variable improving ATP success was use of beta-blockers (81% vs 50%; P = .04). Out of 12 ineffectively treated VTs, one was immediately shocked, four self-terminated after 18 ± 12 s, and seven (18%) were accelerated to a new VT. ATP was also delivered for 27 of 42 inappropriately detected episodes and induced two de novo VTs (7%). In the per patient analysis, 14 out 77 (18%) patients had one or more appropriate and effective ATP (3.4% per year), and only six (8%; 1.4% per year) received more than one ATP.

Conclusion: ATP is moderately effective for the treatment of monomorphic VTs in HCM patients. However, the rate of appropriate ATP therapies is low, ATP is often prematurely delivered, and ATP-induced arrhythmia degeneration is of concern.
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http://dx.doi.org/10.1111/pace.13665DOI Listing
June 2019

Long-Term Left Ventricular Remodeling of Patients With Hypertrophic Cardiomyopathy.

Am J Cardiol 2018 12 8;122(11):1924-1931. Epub 2018 Sep 8.

Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. Electronic address:

In hypertrophic cardiomyopathy (HC), a process of left ventricular (LV) remodeling carrying an adverse prognosis has been described. Conversely, a gradual and benign LV wall thinning has been suggested but never investigated. Therefore, we studied a HC cohort over a long period of time to evaluate the occurrence of a LV remodeling with a benign clinical course. Data of HC patients aged 18 to 65 years and without any condition known to influence LV remodeling were analyzed over a mean follow-up of 7.6 ± 5.7 years. Of 231 HC patients (65% males, mean age 46 ± 12 years), 47 (20%) developed LV remodeling, of whom 23 (10%) had a thinning ≥15% of LV maximal wall thickness from baseline without systolic dysfunction (MWT thinning); 13 (6%) progressed to a LV ejection fraction <50% (end-stage HC) and 11 (5%) developed an apical aneurysm. Follow-up length (odds ratio 1.07, 95% confidence interval 1.00 to 1.15, p = 0.06) and maximal LV wall thickness at baseline (odds ratio 1.14, 95% confidence interval 1.04 to 1.25, p = 0.004) were the main predictors of MWT thinning. Compared with patients with end-stage HC and apical aneurysm, those with MWT thinning showed lower HC-related morbidity (92% and 36% vs 22%, p = 0.003) and mortality (31% and 27% vs 4%, p = 0.02). Furthermore, they showed a combined HC-related morbidity and mortality similar to patients without LV remodeling (incidence 29/1000 vs 26/1000 patient-year, p = 0.77). In conclusion, a process of LV wall thinning with a benign outcome can occur over the long term in patients with HC. The prognostic importance of LV remodeling varies in relation to the different changes in LV morphology and function.
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http://dx.doi.org/10.1016/j.amjcard.2018.08.041DOI Listing
December 2018

Supraventricular arrhythmia with discordant electrocardiographic features: What is the arrhythmia mechanism?

Ann Noninvasive Electrocardiol 2019 03 28;24(2):e12595. Epub 2018 Sep 28.

Arrhythmia & EP Research Center, IRCCS Humanitas Research & University Hospital, Rozzano, Milan, Italy.

Junctional and AV nodal reentrant tachycardia share common electrocardiographic features, but they differ in their management and outcomes after catheter ablation. This case concerns a 60-year-old female who presented with recurrent episodes of a relatively slow, regular supraventricular arrhythmia. Electrocardiographic features of the arrhythmia were discordant regarding its underlying mechanism. However, careful analysis of 12-lead electrocardiograms, with focus on the effect of spontaneous premature beats, pointed out the arrhythmia etiology. Electrophysiological study and pacing maneuvers defined the arrhythmic substrate that was successfully treated by catheter ablation.
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http://dx.doi.org/10.1111/anec.12595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931579PMC
March 2019

An unusual pattern of Para-Hisian pacing: The role of infra-Hisian conduction delay.

J Cardiovasc Electrophysiol 2018 10 22;29(10):1444-1445. Epub 2018 Jun 22.

Arrhythmia and EP Research Center, IRCCS Humanitas Research and University Hospital, Rozzano (Milan), Italy.

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http://dx.doi.org/10.1111/jce.13665DOI Listing
October 2018

Premature ventricular extrastimulus without His or ventricular capture: An unexpected response during AV nodal reentrant tachycardia.

J Cardiovasc Electrophysiol 2018 08 18;29(8):1167-1168. Epub 2018 May 18.

Arrhythmia & EP Research Center, IRCCS Humanitas Research & University Hospital, Rozzano, Milan, Italy.

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http://dx.doi.org/10.1111/jce.13614DOI Listing
August 2018

Autonomic cardiovascular control and cardiac arrhythmia in two pregnant women with hypertrophic cardiomyopathy: Insights from ICD monitoring.

Rev Port Cardiol 2018 04 17;37(4):351.e1-351.e4. Epub 2018 Apr 17.

Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

In women with hypertrophic cardiomyopathy (HCM), pregnancy prompts major changes in hemodynamic and cardiac autonomic function that may precipitate heart failure (HF) or increase the risk of cardiac arrhythmia. We report the clinical follow-up of two patients with non-obstructive HCM implanted with a cardioverter defibrillator (ICD) allowing for continuous analysis of heart rate (HR), heart rate variability (HRV) and cardiac arrhythmia throughout the entire course of pregnancy. Both patients experienced increased HR and decreased HRV from the early stages of pregnancy, which persisted until delivery. Premature ventricular contractions (PVCs) and runs of non-sustained ventricular tachycardia (NSVT) reached a peak in the second and third trimesters, concurrent with sympathetic hyperactivity. In one patient with baseline NYHA class II HF symptoms, increased PVCs and NSVT were consistent with the deterioration of HF, supporting the decision to bring the delivery forward. While both patients experienced a persistent increase in sympathetic tone and ventricular ectopic activity, no life-threatening arrhythmias were documented. During pregnancy, patients with hypertrophic cardiomyopathy develop progressive neuroautonomic imbalance, prompting an increase in non-sustained ventricular arrhythmia. This enhanced arrhythmia burden warrants close follow-up and rhythm assessment during the third trimester, especially in women who have heart failure symptoms before pregnancy. Implantable cardioverter defibrillators provide a continuous analysis of heart rate variability and arrhythmia burden that supports therapeutic decision-making during follow-up.
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http://dx.doi.org/10.1016/j.repc.2017.09.019DOI Listing
April 2018

Safety, Efficacy and Evidence Base for Use of the Subcutaneous Implantable Cardioverter Defibrillator.

J Clin Med 2018 Mar 11;7(3). Epub 2018 Mar 11.

Division of Cardiology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, St. Andrea Hospital, Via di Grottarossa 1035, 00189, Rome, Italy.

The trans-venous implantable cardioverter defibrillator (TV-ICD) is effective in treating life-threatening ventricular arrhythmia and reduces mortality in high-risk patients. However, there are significant short- and long-term complications that are associated with intravascular leads. These shortcomings are mostly relevant in young patients with long life expectancy and low risk of death from non-arrhythmic causes. Drawbacks of trans-venous leads recently led to the development of the entirely subcutaneous implantable cardioverter defibrillator (S-ICD). The S-ICD does not require vascular access or permanent intravascular defibrillation leads. Therefore, it is expected to overcome many complications associated with conventional ICDs. This review highlights data on safety and efficacy of the S-ICD and is envisioned to help in identifying the role of this device in clinical practice.
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http://dx.doi.org/10.3390/jcm7030053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867579PMC
March 2018

Subcutaneous implantable cardioverter defibrillator eligibility according to a novel automated screening tool and agreement with the standard manual electrocardiographic morphology tool.

J Interv Card Electrophysiol 2018 Jun 3;52(1):61-67. Epub 2018 Mar 3.

University Hospital of Pisa, Pisa, Italy.

Purpose: Since subcutaneous implantable cardioverter defibrillator (S-ICD) introduction, the pre-implant screening based on a dedicated manual ECG tool (MST) was required to assure adequate sensing by the S-ICD. A novel automated screening tool (AST) has been recently developed. We assessed and compared the pass rate with AST and MST, and we measured the agreement between screening tools.

Methods: Three electrodes were positioned at locations mimicking the placement of the S-ICD, and ECG recordings were collected in the supine and standing postures at rest. The three sensing vectors were analyzed with the MST and the AST. Eligibility was defined by the presence of at least one or two appropriate vectors in both postures.

Results: A total of 235 patients with an indication to ICD and no need for permanent pacing were enrolled. At least one suitable vector was identified in 214 (91%) patients with MST and 221 (94%) patients with AST (p = 0.219). At least two vectors were appropriate in 162 (69%) patients with MST and 187 (80%) patients with AST (p = 0.008). Overall, out of 1587 ECG analyzed, 1035 (65%) qualifying leads were identified with MST and 1111 (70%) with AST (p = 0.004). The agreement between the results of MST and AST ECG analysis was moderate (Kappa = 0.570; standard error = 0.022; CI = 0.526-0.613). The results were consistent regardless of the underlying cardiomyopathy. The most frequent reason for screening failure with MST was a high-amplitude T-wave (31% of failures). With AST, 23% of recordings that failed with MST for high-amplitude T-wave were classified as acceptable.

Conclusion: The AST is associated with higher pass rate than the standard MST. It seems more tolerant of high-amplitude T-waves. Consequently, the agreement between MST and AST findings was only moderate.
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http://dx.doi.org/10.1007/s10840-018-0326-2DOI Listing
June 2018

Pulmonary hypertension and clinical correlates in hypertrophic cardiomyopathy.

Int J Cardiol 2017 Dec 14;248:326-332. Epub 2017 Jul 14.

Cardiology Division, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy.

Background: Pulmonary hypertension (PH) in patients with hypertrophic cardiomyopathy (HCM) has been investigated in a small number of studies. Purpose of this study was to assess the prevalence and its association with outcome in a population of consecutive HCM outpatients.

Methods: We retrospectively analyzed data of 361 consecutive HCM outpatients in whom echocardiographic measurements of pulmonary artery systolic pressure (PASP) were available at initial and most recent evaluation. Four different clinical groups were specifically investigated: patients without left ventricular outflow tract obstruction (group A, 165), with obstruction (group B, 126), patients diagnosed at the age≥65 (group C, 50) and patients with end stage (ES) HCM (group D, 20).

Results: PH was identified in 41 (11.4%) of the 361 patients at initial evaluation while it has been recognized in 25 (7,8% [1.1%/year]) during a median follow-up of 3.4years. Analysis of subgroups showed that prevalence of PH increased from patient group A to D (8%, group A, 19%, group B, 28% group C, 70%, group D, respectively, p<0,01). During follow-up, patients with PH showed a significant higher HCM-related mortality (p=0.01) and morbidity (p<0.001) as compared with those without PH, but in multivariable analysis, PH resulted an independent risk factor only for HCM-related morbidity (HR=2.50, 95% CI 1.08-5.79, p=0.03).

Conclusion: PH affects a significant proportion of patients with HCM. Its prevalence varies according to different clinical profiles. It is associated with an unfavorable clinical outcome and is an independent predictor of morbidity.
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http://dx.doi.org/10.1016/j.ijcard.2017.07.010DOI Listing
December 2017

Prognostic Implications of Defibrillation Threshold Testing in Patients With Hypertrophic Cardiomyopathy.

J Cardiovasc Electrophysiol 2017 01 14;28(1):103-108. Epub 2016 Dec 14.

Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Introduction: In hypertrophic cardiomyopathy (HCM) patients the need for defibrillation threshold (DFT) testing at the time of ICD implantation is debated. Moreover, its prognostic implications have never been explored. In a cohort of HCM patients we sought to (a) investigate factors prompting DFT testing, (b) evaluate ICD efficacy by testing DFT, (c) compare DFT in patients with and without massive LVH, and (d) assess whether DFT testing predicts shock efficacy for spontaneous VT/VF.

Methods And Results: We retrospectively analyzed a cohort of HCM patients implanted with an ICD. DFT was tested at the discretion of the implanting physician with a 10 J safety margin. During follow-up, ICD interventions were evaluated. The study population included 66 patients. DFT was determined in 25 (38%) patients. Age (HR: 0.95; 95%CI: 0.92-0.98; P = 0.004) and massive LVH (HR: 6.0; 95%CI: 2.03-18.8; P = 0.001) affected the decision to test DFT. DFT was at least 10 J less than maximal ICD output in 25/25. Safety margin was similar among patients with and without massive LVH (15 ± 3 J vs. 14 ± 2 J; P = 0.42). During follow-up (median 53 months) 15 shocks were delivered for 12 VT/VF in 7 patients. One VF ended spontaneously after a failed shock. Of 4 unsuccessful shocks, 2 occurred in 1 patient with DFT testing and 2 were delivered in 2 patients without. All unsuccessful shocks were ≤35 J.

Conclusion: Young age and massive LVH prompt DFT testing. Contemporary ICDs are safe and effective in HCM patients independently from the magnitude of LVH. DFT testing does not predict shock efficacy for spontaneous VT/VF.
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http://dx.doi.org/10.1111/jce.13121DOI Listing
January 2017

Eligibility for the Subcutaneous Implantable Cardioverter-Defibrillator in Patients With Hypertrophic Cardiomyopathy.

J Cardiovasc Electrophysiol 2015 Aug;26(8):893-899

Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Background: High-risk hypertrophic cardiomyopathy (HCM) patients benefit from the implantable cardioverter defibrillator (ICD). The subcutaneous ICD (S-ICD) may provide comparable protection while avoiding the shortcomings of transvenous (TV) leads. We assessed S-ICD eligibility according to surface ECG screening test in a cohort of high-risk HCM patients.

Methods And Results: 47 HCM patients (3 S-ICD candidates; 41 TV-ICD patients without pacing indication; and 3 pacemaker-dependent TV-ICD patients) underwent 4 screening protocols: standard (n = 44); exercise (n = 33); continuous pacing (n = 44); alternating paced/spontaneous QRS (n = 41). Of the 44 patients in the standard screening group, 41 (93%) were eligible. Max LV thickness was inversely related to the number of qualifying leads (3 leads: 21 ± 4 mm; 2 leads: 22 ± 6 mm; 1 lead: 25 ± 6 mm; no leads: 28 ± 11 mm; P = 0.07). Of the 33 patients in the exercise group, 5 were ineligible (3 after exercise). Of these, 2 became eligible after moving sternal electrodes from the left to the right parasternal line (eligibility rate: 30/33; 91%). Of the 44 patients in the continuous pacing group, 28 (64%) were eligible, 8 of which with right parasternal electrodes. In the paced/spontaneous QRS group (n = 41), 21 patients (51%) had at least 1 eligible lead during pacing and retained compatibility on the same lead during spontaneous rhythm, 5 of which with right parasternal electrodes.

Conclusions: S-ICD screening failure is low in HCM, provided that patients with severe hypertrophy are carefully evaluated. Exercise test should be performed and right parasternal leads tested. Pacemaker patients display lower eligibility rate.
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http://dx.doi.org/10.1111/jce.12714DOI Listing
August 2015

RyR2 Common Gene Variant G1886S and the Risk of Ventricular Arrhythmias in ICD Patients with Heart Failure.

J Cardiovasc Electrophysiol 2015 Jun 1;26(6):656-61. Epub 2015 May 1.

Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.

Background: Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel destabilization and enhanced intracellular Ca(2+) oscillation, thus promoting cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is associated with aborted sudden cardiac death or ICD therapy for ventricular tachycardia (VT)/fibrillation (VF) in heart failure (HF) patients implanted with a cardioverter defibrillator (ICD).

Methods And Results: A total of 183 HF patients with primary or secondary prevention ICD were divided in 2 groups. A VT/VF group was composed of secondary prevention patients and primary prevention patients with appropriate ICD intervention for VT/VF. An ICD control group was composed of primary prevention patients free from any appropriate ICD intervention after 43 ± 25 months follow-up. Study subjects were genotyped with respect to the rs3766871 RyR2 gene variant. Hazard ratios (HRs) were derived from Cox proportional-hazards regression analysis. In all, 56 patients constituted the VT/VF group and 127 patients the ICD control group. Male sex (HR: 3.02; 95% CI: 0.99-9.18; P = 0.05), atrial fibrillation (AF; HR: 2.33; 95% CI: 0.89-6.10; P = 0.08), and underuse of β-blockers (HR: 2.08; 95% CI: 0.84-5.15; P = 0.11) were associated with the VT/VF phenotype. Prevalence of the rs3766871 minor allele was 2.8% in ICD control patients and 8.0% in the VT/VF group (P = 0.02). After adjustment for age, sex, AF, and use of β-blockers, the rs3766871 minor allele was associated with increased risk of VT/VF (HR: 3.49; 95% CI: 1.14-10.62; P = 0.02).

Conclusions: Our study identifies a significant role of RyR2 rs3766871 minor allele for increased susceptibility to VT/VF in a population of ICD patients with HF.
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http://dx.doi.org/10.1111/jce.12658DOI Listing
June 2015

P-wave duration in lead aVR and the risk of atrial fibrillation in hypertension.

Ann Noninvasive Electrocardiol 2015 Mar 9;20(2):167-74. Epub 2014 Sep 9.

Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Background: Hypertension entails atrial remodeling that affect P-wave (PW) duration on electrocardiogram (ECG). PW indices (e.g., variance, dispersion, and terminal force) are associated with a higher risk for atrial fibrillation (AF), but their calculation requires multiple measurements of PW duration, limiting their use in clinical practice. We evaluated whether PW duration in specific ECG leads may identify patients with increased susceptibility to AF in a population of hypertensive patients.

Methods: In a case-control study, AF and control subjects were matched for age, sex, and left atrial (LA) dimensions. PW duration was measured from digitally stored ECGs. Logistic regression was used to assess the association of PW duration and indices with AF.

Results: We enrolled 44 hypertensive AF patients (16 paroxysmal and 28 persistent) and 44 hypertensive controls. AF and control subjects were matched for sex (males, n = 27), age (67 ± 8 years), LA diameter (40 ± 5 mm), and were comparable for left ventricular mass (45 ± 11 g/m(2.7) vs 48 ± 12 g/m(2.7) , P = 0.19), ejection fraction (58 ± 7% in both groups), and prevalence of mild valvular heart disease (7% vs 5%; P = 0.64). PW duration in lead aVR was significantly higher in AF patients as compared with controls (115 ± 18 ms vs 101 ± 14 ms; P < 0.0001) and was the best independent predictor of AF in multivariable logistic regression (PW ≥ 100 ms: RR = 3.7; 95% CI: 1.3-10.3; P = 0.02).

Conclusions: Simple measurement of PW duration in lead aVR allows effective identification of AF patients in a population of hypertensives. Confirmation of this finding in a larger population would provide a simple and effective risk marker of AF in hypertensive patients.
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http://dx.doi.org/10.1111/anec.12197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931737PMC
March 2015

Clinical impact of nonsustained ventricular tachycardia recorded by the implantable cardioverter-defibrillator in patients with hypertrophic cardiomyopathy.

J Cardiovasc Electrophysiol 2014 Nov 27;25(11):1180-7. Epub 2014 Aug 27.

Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Background: Nonsustained ventricular tachycardia (NSVT) is a risk factor for sudden death (SD) in hypertrophic cardiomyopathy (HCM). Implantable cardioverter-defibrillators (ICDs) enable accurate assessment of NSVT burden and characteristics. In a cohort of HCM patients with ICD, we characterized Holter- and ICD-retrieved NSVT and evaluated their relationship with prognosis.

Methods And Results: We studied a cohort of consecutive HCM patients who underwent Holter ECG before receiving a primary prevention ICD. Patients were followed from ICD implantation to the first appropriate ICD therapy. We evaluated the association of NSVT characteristics with ICD interventions. Study cohort included 51 HCM patients (28 males, mean age: 48 ± 15 years). Thirty-four patients (66%) had NSVT at pre-ICD Holter ECG. Out of 17 patients with negative baseline Holter, 7 (41%) showed ICD-NSVT. In patients with both Holter- and ICD-NSVT, these latter were faster (199 ± 27 bpm vs. 146 ± 24 bpm; P < 0.001) and longer (16 ± 8 beats vs. 10 ± 11 beats; P = 0.008) than Holter-NSVT. During follow-up (38 ± 24 months), 11 patients (22%) experienced appropriate ICD therapy. NSVT length in beats (hazard ratio [HR]: 1.05; 95% CI: 1.00-1.10; P = 0.02) but not heart rate (HR: 1.00; 95% CI: 0.98-1.02; P = 0.86) predicted ICD intervention. A simple index of NSVT severity (heart rate × length in beats/100 >28) predicted ICD intervention (HR: 5.45; 95% CI: 1.10-27.32; P = 0.03).

Conclusions: Long-lasting and rapid NSVT recorded during continuous rhythm monitoring predict appropriate ICD intervention in high-risk HCM patients. Further studies should assess whether prolonged rhythm monitoring may assist in evaluating patients at intermediate risk of SD, in which the decision to implant an ICD needs to be individualized.
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http://dx.doi.org/10.1111/jce.12492DOI Listing
November 2014

Angiotensin receptor antagonists to prevent sudden death in heart failure: does the dose matter?

ISRN Cardiol 2014 6;2014:652421. Epub 2014 Feb 6.

Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Via di Grottarossa 1035-39, 00189 Rome, Italy ; I.R.C.C.S. Neuromed, Pozzilli, Italy.

International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.
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http://dx.doi.org/10.1155/2014/652421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933036PMC
June 2014

Osteopontin and galectin-3 predict the risk of ventricular tachycardia and fibrillation in heart failure patients with implantable defibrillators.

J Cardiovasc Electrophysiol 2014 Jun 30;25(6):609-16. Epub 2014 Jan 30.

Cardiology, Department of Clinical and Molecular Medicine, University Sapienza, Rome, Italy.

Background: Myocardial extracellular matrix remodelling provides electrical heterogeneity entailing ventricular tachycardia/fibrillation (VT/VF) in heart failure (HF) patients. Osteopontin (OPN) and Galectin-3 (Gal-3) are fibrosis markers and may reflect the extension of the arrhythmogenic substrate. We assessed whether plasma OPN and Gal-3 predict the risk of sustained VT/VF in a cohort of HF patients with implantable cardioverter-defibrillator (ICD).

Methods: A total of 75 HF patients underwent pre-ICD implantation clinical evaluation and assessment of plasma OPN and Gal-3. The primary endpoint was the time to the occurrence of the first sustained VT/VF. Hazard ratios (HR) were derived from Cox proportional-hazards analysis.

Results: Patients with coronary artery disease (CAD) had higher plasma OPN (79.8 ± 44.0 ng/mL vs. 66.0 ± 31.8 ng/mL; P = 0.04). Both Gal-3 (r = -0.38; P = 0.01) and OPN (r = -0.27; p = 0.01) were negatively related to estimated glomerular filtration rate. After 29 ± 17 months, 20 patients (27%) reached the primary endpoint. Patients with VT/VF had higher plasma OPN and Gal-3 (97.4 ± 51.7 ng/mL vs. 65.9 ± 31.3 ng/mL; P = 0.002 and 19.7 ± 8.5 ng/mL vs. 16.2 ± 6.2 ng/mL; P = 0.05). In univariate analysis, OPN (log-OPN, HR: 32.4; 95%CI: 3.9-264.7; P = 0.001) and Gal-3 (HR: 1.05; 95%CI: 1.00-1.11; P = 0.04) predicted sustained VT/VF. In multivariable analysis, both OPN (HR: 41.4; 95%CI: 3.8-441.9; P = 0.002) and Gal-3 (HR: 1.06; 95%CI: 1.00-1.12; P = 0.03) retained their prognostic power after correction for age, sex, history of MI, EF, NYHA class, eGFR, use of ACE-I, and amiodarone.

Conclusions: Plasma OPN and Gal-3 predict sustained VT/VF in HF patients at high risk for SCD. Larger prospective studies should outline the role of these biomarkers in predicting SCD on top of conventional risk stratification.
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http://dx.doi.org/10.1111/jce.12364DOI Listing
June 2014

Atrial natriuretic Peptide single nucleotide polymorphisms in patients with nonfamilial structural atrial fibrillation.

Clin Med Insights Cardiol 2013 15;7:153-9. Epub 2013 Sep 15.

Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Background: Atrial natriuretic peptide (ANP) has antihypertrophic and antifibrotic properties that are relevant to AF substrates. The -G664C and rs5065 ANP single nucleotide polymorphisms (SNP) have been described in association with clinical phenotypes, including hypertension and left ventricular hypertrophy. A recent study assessed the association of early AF and rs5065 SNPs in low-risk subjects. In a Caucasian population with moderate-to-high cardiovascular risk profile and structural AF, we conducted a case-control study to assess whether the ANP -G664C and rs5065 SNP associate with nonfamilial structural AF.

Methods: 168 patients with nonfamilial structural AF and 168 age- and sex-matched controls were recruited. The rs5065 and -G664C ANP SNPs were genotyped.

Results: The study population had a moderate-to-high cardiovascular risk profile with 86% having hypertension, 23% diabetes, 26% previous myocardial infarction, and 23% left ventricular systolic dysfunction. Patients with AF had greater left atrial diameter (44 ± 7 vs. 39 ± 5 mm; P < 0.001) and higher plasma NTproANP levels (6240 ± 5317 vs. 3649 ± 2946 pmol/mL; P < 0.01). Odds ratios (ORs) for rs5065 and -G664C gene variants were 1.1 (95% confidence interval [CI], 0.7-1.8; P = 0.71) and 1.2 (95% CI, 0.3-3.2; P = 0.79), respectively, indicating no association with AF. There were no differences in baseline clinical characteristics among carriers and noncarriers of the -664C and rs5065 minor allele variants.

Conclusions: We report lack of association between the rs5065 and -G664C ANP gene SNPs and AF in a Caucasian population of patients with structural AF. Further studies will clarify whether these or other ANP gene variants affect the risk of different subphenotypes of AF driven by distinct pathophysiological mechanisms.
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http://dx.doi.org/10.4137/CMC.S12239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782394PMC
October 2013

Common genetic variants in selected Ca²⁺ signaling genes and the risk of appropriate ICD interventions in patients with heart failure.

J Interv Card Electrophysiol 2013 Dec 19;38(3):169-77. Epub 2013 Sep 19.

Division of Cardiology, Department of Clinical and Molecular Medicine, Sapienza University of Rome Sant'Andrea Hospital, Via di Grottarossa, 00189, Rome, Italy,

Purpose: Defective Ca²⁺ handling in failing cardiomyocites predisposes patients with heart failure (HF) to ventricular arrhythmia. We investigated whether gene variants of Ca²⁺ handling proteins are associated with the occurrence of ventricular tachycardia/fibrillation (VT/VF) in HF patients implanted with a primary prevention implantable cardioverter-defibrillator (ICD).

Methods: One hundred thirty-six patients with HF were followed from ICD implantation to the time of first appropriate ICD intervention for VT > 170 bpm. The following polymorphisms were genotyped: ATP2A2 rs1860561 and rs56243033; RYR2 rs4142933; CASQ2 rs4074536; SLC8A1 g.-23449C > A; PLN rs12198461; FKBP1B rs7568163. Hazard ratios (HR) were derived from Cox proportional-hazards regression analysis.

Results: After a mean follow-up of 879 days (IQ range, 327 to 1,459), 34 patients (25%) had appropriate ICD intervention. Non-sustained VT (HR, 2.12; 95%CI, 0.87-5.19; p = 0.09) and atrial fibrillation (AF) at ICD implantation (HR, 2.33; 95%CI, 0.89-6.10; p = 0.08) predicted appropriate ICD interventions with borderline statistical significance. Prevalence of ATP2A2 rs1860561 variant was 17% in patients without VT/VF and 4% in those with ventricular arrhythmia (p = 0.009). After adjustment for AF and NSVT, the rs1860561 A mutant allele independently predicted lower incidence of VT/VF (HR, 0.29; 95%CI, 0.09-0.98; p = 0.04).

Conclusions: The observation that ATP2A2 rs1860561 gene variant associated with lower risk of life-threatening arrhythmia in HF patients suggests that selected calcium gene variants may modify the risk of SD even within the complex and polygenic pathological condition of HF. Combining traditional risk factors and genetic profiling could reveal helpful to identify HF patients who will benefit most from ICD implantation.
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http://dx.doi.org/10.1007/s10840-013-9827-1DOI Listing
December 2013

New oral anticoagulants in non-valvular atrial fibrillation.

High Blood Press Cardiovasc Prev 2013 Jun 8;20(2):53-60. Epub 2013 May 8.

Division of Cardiology, Department of Clinical and Molecular Medicine, University of Rome Sapienza, Sant'Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy.

Atrial fibrillation (AF) is associated with an increased risk of embolic stroke. Dose-adjusted vitamin K antagonists (VKAs) to a target international normalized ratio (INR) range of 2.0-3.0 reduce the risk of ischemic stroke and are currently recommended in all patients with AF at moderate-high risk for stroke or systemic embolism. However, VKAs have several drawbacks, including unpredictable anticoagulant response, food and drug interactions, need for regular laboratory monitoring and dose adjustment. These limitations prompted the introduction of new oral anticoagulants (NOA) that target thrombin and factor Xa, key-enzymes in the coagulation pathway. NOA have predictable pharmacodynamics, allowing fixed dosing without the need of laboratory monitoring, and have few drug and food interactions. The present review focuses on pharmacological properties, safety, and appropriate clinical use of dabigatran, rivaroxaban and apixaban.
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http://dx.doi.org/10.1007/s40292-013-0011-6DOI Listing
June 2013