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Sacchi L.,University of Pavia | Rubrichi S.,University of Pavia | Rognoni C.,University of Pavia | Rognoni C.,Bocconi University | And 7 more authors.
Artificial Intelligence in Medicine | Year: 2015

Objective: Taking into account patients' preferences has become an essential requirement in health decision-making. Even in evidence-based settings where directions are summarized into clinical practice guidelines, there might exist situations where it is important for the care provider to involve the patient in the decision. In this paper we propose a unified framework to promote the shift from a traditional, physician-centered, clinical decision process to a more personalized, patient-oriented shared decision-making (SDM) environment. Methods: We present the theoretical, technological and architectural aspects of a framework that encapsulates decision models and instruments to elicit patients' preferences into a single tool, thus enabling physicians to exploit evidence-based medicine and shared decision-making in the same encounter. Results: We show the implementation of the framework in a specific case study related to the prevention and management of the risk of thromboembolism in atrial fibrillation. We describe the underlying decision model and how this can be personalized according to patients' preferences. The application of the framework is tested through a pilot clinical evaluation study carried out on 20 patients at the Rehabilitation Cardiology Unit at the IRCCS Fondazione Salvatore Maugeri hospital (Pavia, Italy). The results point out the importance of running personalized decision models, which can substantially differ from models quantified with population coefficients. Conclusions: This study shows that the tool is potentially able to overcome some of the main barriers perceived by physicians in the adoption of SDM. In parallel, the development of the framework increases the involvement of patients in the process of care focusing on the centrality of individual patients. © 2014 Elsevier B.V.


Monteforte N.,Molecular Cardiology Laboratories | Cerrone M.,New York University
Cardiac Electrophysiology Clinics | Year: 2010

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease characterized by a structurally normal heart and high lethality beginning in early childhood. The identification of its genetic bases made possible the discovery that arrhythmias are caused by intracellular calcium dysregulation. In the 9 years since the description of the genetic substrate of the disease, we have witnessed remarkable progress in the unraveling of the molecular mechanisms underlying its arrhythmogenesis. The impact of these discoveries extends beyond the field of inherited arrhythmias and sheds new light on the arrhythmogenic mechanisms in some more prevalent diseases characterized by abnormal calcium regulation, such as heart failure. Additionally, basic research studies led to the exploration of new therapeutic strategies with potential clinical impact in the near future in reducing the still high incidence of sudden death associated with these conditions. In the current review, the authors discuss the clinical and genetic features of CPVT, highlighting pathophysiologic insights derived from experimental research and future therapeutic targets. © 2010 Elsevier Inc.


Corona-Rivera J.R.,Dr Juan I Menchaca Civil Hospital Of Guadalajara | Corona-Rivera J.R.,University of Guadalajara | Barrios-Prieto E.,Dr Juan I Menchaca Civil Hospital Of Guadalajara | Nieto-Garcia R.,Dr Juan I Menchaca Civil Hospital Of Guadalajara | And 11 more authors.
European Journal of Medical Genetics | Year: 2015

Timothy syndrome 1 (TS1) is a multisystem disorder characterized by severe QT prolongation and potentially lethal ventricular arrhythmias in the first years of life, plus other cardiac and extracardiac manifestations caused by mutation in the CACNA1C gene, a CaV1.2 L-type calcium channel. Here, we report retrospectively an unusual fetal presentation on a second patient with TS1 with fetal hydrops due to a congenital AV block and its postnatal diagnosis by a marked prolongation of the corrected QTc interval of 570 ms and a missense mutation, p.Gly406Arg, in exon 8A of CACNA1C gene. The observed manifestations in our patient during fetal period indicate a severe form and they were probably exacerbated by the maternal use of amitriptyline during the first 4 months of pregnancy. Unfortunately, he died at 3 months-old due a ventricular tachycardia and fibrillation related to a septic event. Although difficult to diagnose, possibly most fetuses with TS1 have symptoms of long QT syndrome. Despite the fatal outcome for our patient, an early diagnosis of TS may help to prevent life-threatening events or early death in future patients, especially in developing countries where availability of therapies such as cardioverter defibrillator are very limited, or require time for its funding. © 2015 Elsevier Masson SAS.


Napolitano C.,Molecular Cardiology Laboratories | Napolitano C.,New York University
Pediatric Cardiology | Year: 2012

Syncope and risk of sudden death due to ventricular tachyarrhythmia are the common manifestations of several inherited disorders. Abnormalities of the genetic makeup may directly affect proteins controlling cardiac excitability in a structurally normal heart. Other diseases manifest primarily with ventricular arrhythmias even though the genetic mutations cause structural abnormalities of the myocardium. This is the case of arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy. Groundbreaking discoveries, starting from the 1990s until the beginning of the current decade, have provided fundamental knowledge on the major genes that confer an increased risk of arrhythmias and sudden death. Stems of such knowledge are the availability of genetic diagnosis, genotype-phenotype correlation, and genotypebased risk stratification schemes currently used in the clinical practice. This review provides a concise description of the known genes and key mechanisms involved in the pathogenesis of inherited arrhythmias. In addition, we outline possibilities, limitations, advantages, and potential threats of genetically screening for these genes. © Springer Science+Business Media, LLC 2012.


Napolitano C.,Molecular Cardiology Laboratories | Novelli V.,Molecular Cardiology Laboratories | Francis M.D.,Molecular Cardiology Laboratories | Priori S.G.,University of Pavia
Current Opinion in Genetics and Development | Year: 2015

Long QT syndrome (LQTS) is one the best characterized disorders among all inherited arrhythmogenic syndromes. A multi-parametric risk stratification scheme, which includes clinical variables (QTc, gender) and the main LQTS genotypes, was defined in the early 2000s and is currently used in clinical practice. However, the evidence of a marked phenotypic variability, even in the presence of the same genetic mutation has puzzled many investigators since the discovery of LQTS genes. Practically, variable expression in LQTS often limits the predictive accuracy of risk stratification markers. Therefore, in a subset of cases, the identification of subjects at a high risk of life-threatening arrhythmias and sudden death is difficult. The discovery of common genetic variants that explain the heritable components of the human electrocardiogram, including QT interval, generated the hypothesis that genetic modifiers may account for phenotypical variability in LQTS. Despite the fact that multiple SNPs have been linked to QT interval duration, clinical applications of any findings are limited by the small effect sizes conferred by single SNPs and incomplete knowledge on their functional consequences. Nevertheless, the possibility of introducing SNP genotyping in risk stratification schemes to improve patient-specificity is an attractive goal. Here we review the currently available evidence and future perspectives for the inclusion of genetic modifiers in the clinical management of LQTS. © 2015 Elsevier Ltd.


PubMed | Molecular Cardiology Laboratories
Type: Journal Article | Journal: Pediatric cardiology | Year: 2012

Syncope and risk of sudden death due to ventricular tachyarrhythmia are the common manifestations of several inherited disorders. Abnormalities of the genetic makeup may directly affect proteins controlling cardiac excitability in a structurally normal heart. Other diseases manifest primarily with ventricular arrhythmias even though the genetic mutations cause structural abnormalities of the myocardium. This is the case of arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy. Groundbreaking discoveries, starting from the 1990s until the beginning of the current decade, have provided fundamental knowledge on the major genes that confer an increased risk of arrhythmias and sudden death. Stems of such knowledge are the availability of genetic diagnosis, genotype-phenotype correlation, and genotype-based risk stratification schemes currently used in the clinical practice. This review provides a concise description of the known genes and key mechanisms involved in the pathogenesis of inherited arrhythmias. In addition, we outline possibilities, limitations, advantages, and potential threats of genetically screening for these genes.


PubMed | Molecular Cardiology Laboratories and University of Pavia
Type: Journal Article | Journal: Artificial intelligence in medicine | Year: 2015

Taking into account patients preferences has become an essential requirement in health decision-making. Even in evidence-based settings where directions are summarized into clinical practice guidelines, there might exist situations where it is important for the care provider to involve the patient in the decision. In this paper we propose a unified framework to promote the shift from a traditional, physician-centered, clinical decision process to a more personalized, patient-oriented shared decision-making (SDM) environment.We present the theoretical, technological and architectural aspects of a framework that encapsulates decision models and instruments to elicit patients preferences into a single tool, thus enabling physicians to exploit evidence-based medicine and shared decision-making in the same encounter.We show the implementation of the framework in a specific case study related to the prevention and management of the risk of thromboembolism in atrial fibrillation. We describe the underlying decision model and how this can be personalized according to patients preferences. The application of the framework is tested through a pilot clinical evaluation study carried out on 20 patients at the Rehabilitation Cardiology Unit at the IRCCS Fondazione Salvatore Maugeri hospital (Pavia, Italy). The results point out the importance of running personalized decision models, which can substantially differ from models quantified with population coefficients.This study shows that the tool is potentially able to overcome some of the main barriers perceived by physicians in the adoption of SDM. In parallel, the development of the framework increases the involvement of patients in the process of care focusing on the centrality of individual patients.


PubMed | University of Pavia and Molecular Cardiology Laboratories
Type: | Journal: Current opinion in genetics & development | Year: 2015

Long QT syndrome (LQTS) is one the best characterized disorders among all inherited arrhythmogenic syndromes. A multi-parametric risk stratification scheme, which includes clinical variables (QTc, gender) and the main LQTS genotypes, was defined in the early 2000s and is currently used in clinical practice. However, the evidence of a marked phenotypic variability, even in the presence of the same genetic mutation has puzzled many investigators since the discovery of LQTS genes. Practically, variable expression in LQTS often limits the predictive accuracy of risk stratification markers. Therefore, in a subset of cases, the identification of subjects at a high risk of life-threatening arrhythmias and sudden death is difficult. The discovery of common genetic variants that explain the heritable components of the human electrocardiogram, including QT interval, generated the hypothesis that genetic modifiers may account for phenotypical variability in LQTS. Despite the fact that multiple SNPs have been linked to QT interval duration, clinical applications of any findings are limited by the small effect sizes conferred by single SNPs and incomplete knowledge on their functional consequences. Nevertheless, the possibility of introducing SNP genotyping in risk stratification schemes to improve patient-specificity is an attractive goal. Here we review the currently available evidence and future perspectives for the inclusion of genetic modifiers in the clinical management of LQTS.


PubMed | Molecular Cardiology Laboratories
Type: Journal Article | Journal: Circulation research | Year: 2011

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease occurring in patients with a structurally normal heart: the disease is characterized by life-threatening arrhythmias elicited by stress and emotion. In 2001, the ryanodine receptor was identified as the gene that is linked to CPVT; shortly thereafter, cardiac calsequestrin was implicated in the recessive form of the same disease. It became clear that abnormalities in intracellular Ca(2+) regulation could profoundly disrupt the electrophysiological properties of the heart. In this article, we discuss the molecular basis of the disease and the pathophysiological mechanisms that are impacting clinical diagnosis and management of affected individuals. As of today, the interaction between basic scientists and clinicians to understand CPVT and identify new therapeutic strategies is one of the most compelling examples of the importance of translational research in cardiology.


PubMed | Dr Juan I Menchaca Civil Hospital Of Guadalajara, Molecular Cardiology Laboratories and University of Guadalajara
Type: Case Reports | Journal: European journal of medical genetics | Year: 2015

Timothy syndrome 1 (TS1) is a multisystem disorder characterized by severe QT prolongation and potentially lethal ventricular arrhythmias in the first years of life, plus other cardiac and extracardiac manifestations caused by mutation in the CACNA1C gene, a CaV1.2L-type calcium channel. Here, we report retrospectively an unusual fetal presentation on a second patient with TS1 with fetal hydrops due to a congenital AV block and its postnatal diagnosis by a marked prolongation of the corrected QTc interval of 570ms and a missense mutation, p.Gly406Arg, in exon 8A of CACNA1C gene. The observed manifestations in our patient during fetal period indicate a severe form and they were probably exacerbated by the maternal use of amitriptyline during the first 4 months of pregnancy. Unfortunately, he died at 3 months-old due a ventricular tachycardia and fibrillation related to a septic event. Although difficult to diagnose, possibly most fetuses with TS1 have symptoms of long QT syndrome. Despite the fatal outcome for our patient, an early diagnosis of TS may help to prevent life-threatening events or early death in future patients, especially in developing countries where availability of therapies such as cardioverter defibrillator are very limited, or require time for its funding.

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