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1.
Eur Heart J ; 45(32): 2968-2979, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39011630

RESUMEN

BACKGROUND AND AIMS: Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population. METHODS: Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86). RESULTS: In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%. CONCLUSIONS: The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach.


Asunto(s)
Desmoplaquinas , Humanos , Desmoplaquinas/genética , Femenino , Masculino , Medición de Riesgo/métodos , Adulto , Persona de Mediana Edad , Arritmias Cardíacas/genética , Heterocigoto , Taquicardia Ventricular/genética
2.
Eur Heart J ; 45(7): 538-548, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38195003

RESUMEN

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.


Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Desfibriladores Implantables , Humanos , Desfibriladores Implantables/efectos adversos , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/epidemiología , Displasia Ventricular Derecha Arritmogénica/terapia , Estudios Retrospectivos , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/terapia , Arritmias Cardíacas/etiología , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología , Factores de Riesgo , América del Norte/epidemiología , Europa (Continente)/epidemiología
3.
Value Health ; 27(7): 897-906, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38548178

RESUMEN

OBJECTIVES: This study aims to show the application of flexible statistical methods in real-world cost-effectiveness analyses applied in the cardiovascular field, focusing specifically on the use of proprotein convertase subtilisin-kexin type 9 inhibitors for hyperlipidemia. METHODS: The proposed method allowed us to use an electronic health database to emulate a target trial for cost-effectiveness analysis using multistate modeling and microsimulation. We formally established the study design and provided precise definitions of the causal measures of interest while also outlining the assumptions necessary for accurately estimating these measures using the available data. Additionally, we thoroughly considered goodness-of-fit assessments and sensitivity analyses of the decision model, which are crucial to capture the complexity of individuals' healthcare pathway and to enhance the validity of this type of health economic models. RESULTS: In the disease model, the Markov assumption was found to be inadequate, and a "time-reset" timescale was implemented together with the use of a time-dependent variable to incorporate past hospitalization history. Furthermore, the microsimulation decision model demonstrated a satisfying goodness of fit, as evidenced by the consistent results obtained in the short-term horizon compared with a nonmodel-based approach. Notably, proprotein convertase subtilisin-kexin type 9 inhibitors revealed their favorable cost-effectiveness only in the long-term follow-up, with a minimum willingness to pay of 39 000 Euro/life years gained. CONCLUSIONS: The approach demonstrated its significant utility in several ways. Unlike nonmodel-based or alternative model-based methods, it enabled to (1) investigate long-term cost-effectiveness comprehensively, (2) use an appropriate disease model that aligns with the specific problem under study, and (3) conduct subgroup-specific cost-effectiveness analyses to gain more targeted insights.


Asunto(s)
Análisis Costo-Beneficio , Modelos Económicos , Inhibidores de PCSK9 , Humanos , Años de Vida Ajustados por Calidad de Vida , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/economía , Simulación por Computador , Cadenas de Markov , Masculino , Femenino , Persona de Mediana Edad , Anciano , Proproteína Convertasa 9
4.
BMC Med Res Methodol ; 23(1): 169, 2023 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-37481514

RESUMEN

BACKGROUND: Machine learning (ML) methods to build prediction models starting from electrocardiogram (ECG) signals are an emerging research field. The aim of the present study is to investigate the performances of two ML approaches based on ECGs for the prediction of new-onset atrial fibrillation (AF), in terms of discrimination, calibration and sample size dependence. METHODS: We trained two models to predict new-onset AF: a convolutional neural network (CNN), that takes as input the raw ECG signals, and an eXtreme Gradient Boosting model (XGB), that uses the signal's extracted features. A penalized logistic regression model (LR) was used as a benchmark. Discrimination was evaluated with the area under the ROC curve, while calibration with the integrated calibration index. We investigated the dependence of models' performances on the sample size and on class imbalance corrections introduced with random under-sampling. RESULTS: CNN's discrimination was the most affected by the sample size, outperforming XGB and LR only around n = 10.000 observations. Calibration showed only a small dependence on the sample size for all the models considered. Balancing the training set with random undersampling did not improve discrimination in any of the models. Instead, the main effect of imbalance corrections was to worsen the models' calibration (for CNN, integrated calibration index from 0.014 [0.01, 0.018] to 0.17 [0.16, 0.19]). The sample size emerged as a fundamental point for developing the CNN model, especially in terms of discrimination (AUC = 0.75 [0.73, 0.77] when n = 10.000, AUC = 0.80 [0.79, 0.81] when n = 150.000). The effect of the sample size on the other two models was weaker. Imbalance corrections led to poorly calibrated models, for all the approaches considered, reducing the clinical utility of the models. CONCLUSIONS: Our results suggest that the choice of approach in the analysis of ECG should be based on the amount of data available, preferring more standard models for small datasets. Moreover, imbalance correction methods should be avoided when developing clinical prediction models, where calibration is crucial.


Asunto(s)
Fibrilación Atrial , Humanos , Fibrilación Atrial/diagnóstico , Calibración , Electrocardiografía , Benchmarking , Aprendizaje Automático
5.
Cardiology ; 148(3): 257-268, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37040728

RESUMEN

BACKGROUND: Psychoactive substances have toxic effects resulting different cardiovascular and non-cardiovascular organ damage. Through a variety of mechanisms, they can trigger the onset of various forms of cardiovascular disease: acute or chronic, transient or permanent, subclinical or symptomatic. Hence, a thorough knowledge of the patient's drug habits is essential for a more complete clinical-etiopathogenetic diagnosis and consequent therapeutic, preventive, and rehabilitative management. SUMMARY: The prime reason for taking a psychoactive substance use history in the cardiovascular context is to identify those people who use substances (whether habitual or occasional users, symptomatic or not) and adequately assess their overall cardiovascular risk profile in terms of "user status" and type of substance(s) used. A psychoactive substance history could also alert the physician to suspect, and eventually diagnose, cardiovascular disease related to the intake of psychoactive substances, so optimizing the medical management of users. This anamnesis could finally assess the likelihood of patients persisting in the habit as a user or relapse, while maintaining high their cardiovascular risk profile. Taking such a history should be mandatory when a causal connection is suspected between intake of psychoactive substances and the observed symptoms or pathology, regardless of whether the individual is a declared user or not. KEY MESSAGES: The purpose of this article was to provide practical information on when, how, and why to perform a psychoactive substance use history.


Asunto(s)
Enfermedades Cardiovasculares , Trastornos Relacionados con Sustancias , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Factores de Riesgo , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/diagnóstico , Psicotrópicos/efectos adversos , Factores de Riesgo de Enfermedad Cardiaca
6.
Eur Heart J Suppl ; 25(Suppl B): B69-B74, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37091642

RESUMEN

Left ventricular (LV) systolic function is an essential parameter for the evaluation of patients with ischaemic heart disease, and therapeutic choices are significantly driven by LV ejection fraction (LVEF) in the early stage of the disease and during follow-up. After an acute coronary syndrome, ventricular dysfunction may be reversible when caused by transient myocardial stunning. Therefore, the identification of clinical, laboratory, and instrumental predictors of improvement in LV systolic function (in addition to LVEF) is essential for an adequate prognostic stratification. In the setting of chronic ischaemic heart disease, there is no evidence that an improvement in LV systolic function is invariably associated with a better prognosis and LVEF is only one of many parameters that should be considered for the risk stratification. This state-of-the-art review will critically analyse the scientific evidence regarding known predictors of LVEF recovery, trying to elucidate their pathophysiological principles and clinical value.

7.
Eur Heart J ; 43(32): 3053-3067, 2022 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-35766183

RESUMEN

AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.


Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Arritmias Cardíacas , Displasia Ventricular Derecha Arritmogénica/genética , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Genotipo , Humanos , Medición de Riesgo , Factores de Riesgo
8.
Biom J ; 64(8): 1374-1388, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36058642

RESUMEN

In many clinical applications to evaluate the effect of a treatment, randomized control trials are difficult to carry out. On the other hand, clinical observational registries are often available and they contain longitudinal data regarding clinical parameters, drug therapies, and outcomes. In the past, much research has addressed causal methods to estimate treatment effects from observational studies. In the context of time-varying treatments, marginal structural models are often used. However, most analyses have focused on binary outcomes or time-to-the-first event analyses. The novelty of our approach is to combine the marginal structural methodology with the case where correlated recurrent events and survival are the outcomes of interest. Our work focuses on solving the nontrivial problem of defining the measures of effect, specifying the model for the time-dependent weights and the model to estimate the outcome, implementing them, and finally estimating the final treatment effects in this life-history setting. Our approach provides a strategy that allows obtaining treatment effect estimates both on the recurrent events and the survival with a clear causal and clinical interpretation. At the same time, the strategy we propose is based on flexible modeling choices such as the use of joint models to capture the correlation within events from the same subject and the specification of time-dependent treatment effects. The clinical problem which motivated our work is the evaluation of the treatment effect of beta-blockers in arrhythmogenic right ventricular cardiomyopathy (ARVC/D), and the dataset comes from the Trieste Heart Muscle Disease Registry.


Asunto(s)
Cardiomiopatías , Sistema de Registros
9.
Heart Fail Clin ; 18(1): 101-113, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34776072

RESUMEN

In the wide phenotypic spectrum of cardiomyopathies, sudden cardiac death (SCD) has always been the most visible and devastating disease complication. The introduction of implantable cardioverter-defibrillators for SCD prevention by the late 1980s has moved the question from how to whom we should protect from SCD, leaving clinicians with a measure of uncertainty regarding the most reliable option to guide identification of the highest-risk patients. In this review, we will go through all the available evidence in the field of arrhythmic expression and arrhythmic risk stratification in the different phenotypes of cardiomyopathies to provide practical suggestions in daily clinical management.


Asunto(s)
Cardiomiopatías , Desfibriladores Implantables , Cardiomiopatías/genética , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Humanos , Fenotipo
10.
Eur Heart J Suppl ; 22(Suppl L): L129-L135, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33239987

RESUMEN

Arrhythmogenic right ventricular cardiomyopathy is a myocardial disease generally caused by desmosomal mutations and characterized by progressive replacement of cardiomyocites with fibro-adipose tissue. In the classic form of the disease right ventricle is predominantly affected. However, biventricular and left-dominant variants have been recently recognized, leading to the new nosological definition of arrhythmogenic cardiomyopathy. The condition affects mostly young adults and athletes and is clinically characterized by ventricular arrhythmias, heart failure and sudden cardiac death. The diagnosis is based on clinical-instrumental criteria, including family history, morpho-functional and electrocardiographic abnormalities, ventricular arrhythmias and genetic defects (Task Force Criteria, 2010). The main goal in the management of patients is the prevention of sudden cardiac death, where implantable cardioverter-defibrillator is the only effective therapeutic strategy. Many arrhythmic risk factors have been described. Recently, an on-line calculator has been proposed, but it needs further validation.

11.
Curr Cardiol Rep ; 22(12): 169, 2020 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-33040219

RESUMEN

PURPOSE OF REVIEW: Cardiac masses frequently present significant diagnostic and therapeutic clinical challenges and encompass a broad set of lesions that can be either neoplastic or non-neoplastic. We sought to provide an overview of cardiac tumors using a cardiac chamber prevalence approach and providing epidemiology, imaging, histopathology, diagnostic workup, treatment, and prognoses of cardiac tumors. RECENT FINDINGS: Cardiac tumors are rare but remain an important component of cardio-oncology practice. Over the past decade, the advances in imaging techniques have enabled a noninvasive diagnosis in many cases. Indeed, imaging modalities such as cardiac magnetic resonance, computed tomography, and positron emission tomography are important tools for diagnosing and characterizing the lesions. Although an epidemiological and multimodality imaging approach is useful, the definite diagnosis requires histologic examination in challenging scenarios, and histopathological characterization remains the diagnostic gold standard. A comprehensive clinical and multimodality imaging evaluation of cardiac tumors is fundamental to obtain a proper differential diagnosis, but histopathology is necessary to reach the final diagnosis and subsequent clinical management.


Asunto(s)
Neoplasias Cardíacas , Imagen por Resonancia Magnética , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/epidemiología , Humanos , Imagen Multimodal , Tomografía de Emisión de Positrones , Pronóstico
12.
Europace ; 21(2): 332-338, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30169617

RESUMEN

AIMS: To characterize the most common electrocardiographic (ECG) abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), including anterior T-wave inversion (TWI) and to compare the characteristics of TWI in patients with ARVC and in a cohort of young healthy athletes and sedentary individuals. METHODS AND RESULTS: The study population consisted of 162 patients with a definite diagnosis of ARVC and 129 young controls with anterior TWI. Cardiac disease was excluded in all controls after a comprehensive diagnostic work-up. The ECG was abnormal in 131 patients with ARVC (81%). Abnormalities included anterior TWI (n = 82, 51%), QRS duration ratio V2:V5 >1.2 (n = 51, 31%), prolonged terminal S wave activation duration in V2 >55 ms (n = 42, 26%), inferior TWI (n = 30, 18%), and lateral TWI (n = 26, 16%). The J-point preceding anterior TWI was <0.1 mV in 80/82 (98%) patients with ARVC and in 98 (76%) controls. Among the ARVC patients with anterior TWI, 62 (77%) showed at least one additional abnormal feature, most commonly QRS duration ratio V2:V5 > 1.2 (52%) and inferior or lateral TWI (47%). CONCLUSION: The ECG is frequently abnormal in patients with ARVC and anterior TWI is the most common feature. Anterior TWI is usually accompanied by other abnormalities in ARVC, which are uncommon in healthy individuals. J point <0.1 mV preceding anterior TWI is not specific to ARVC and is observed in the majority of healthy individuals, including athletes, indicating a limited role for differentiating physiology or normal variants from ARVC.


Asunto(s)
Potenciales de Acción , Arritmias Cardíacas/diagnóstico , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Adulto , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/fisiopatología , Displasia Ventricular Derecha Arritmogénica/epidemiología , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Atletas , Estudios de Casos y Controles , Estudios Transversales , Diagnóstico Diferencial , Femenino , Frecuencia Cardíaca , Humanos , Italia/epidemiología , Londres/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Conducta Sedentaria
13.
Europace ; 20(FI1): f20-f29, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28633348

RESUMEN

Aims: The arrhythmic risk stratification of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains controversial. We evaluated the long-term distribution of life-threatening arrhythmic events assessing the impact of periodical risk reassessment. Methods and results: Ninety-eight ARVC patients with no previous major ventricular arrhythmias were retrospectively analysed. Patients were assessed at baseline, at 22 [inter-quartile range (IQR) 16-26], 49 (IQR 41-55) and 97 months (IQR 90-108). The primary endpoint was a composite of sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or appropriate implanted cardioverter-defibrillator intervention. During a median follow-up of 91 months (IQR 34-222) 28 patients (29%) experienced the composite endpoint. The median time for the primary event was 35 months (IQR 18-86 months), and 39% of events occurred beyond 49 months of follow-up. History of syncope (HR 4.034; 95% CI, 1.488 to 10.932; P-value = 0.006), non-sustained ventricular tachycardia (NSVT; HR 3.534; 95% CI 1.265-9.877; P-value = 0.016), premature ventricular contractions (PVC) >1000/24h (HR 2.761; 95% CI 1.120-6.807; P-value = 0.027), and right ventricular fractional area change (RVFAC; HR 0.945; 95% CI 0.906-0.985; P-value = 0.008) were found as independent predictors at baseline multivariate analysis. Nevertheless, when the prognostic impact of each variable was reassessed overtime only NSVT (HR 3.282; 95% CI, 1.122 to 9.598, P-value = 0.023) and RVFAC (HR 0.351, 95% CI, 0.157 to 0.780; P-value = 0.010) remained independent predictors throughout the whole follow-up. Conclusion: In our cohort of ARVC patients only NSVT and RVFAC maintained their independent prognostic impact in predicting arrhythmic events during the long-term follow-up. Periodical re-assessment of risk in these patients is strongly recommended.


Asunto(s)
Potenciales de Acción , Displasia Ventricular Derecha Arritmogénica/complicaciones , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatología , Taquicardia Ventricular/etiología , Fibrilación Ventricular/etiología , Potenciales de Acción/efectos de los fármacos , Adulto , Antiarrítmicos/uso terapéutico , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Displasia Ventricular Derecha Arritmogénica/terapia , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Cardioversión Eléctrica/instrumentación , Electrocardiografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/prevención & control , Factores de Tiempo , Resultado del Tratamiento , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/prevención & control , Adulto Joven
14.
PLoS One ; 19(8): e0309470, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39173034

RESUMEN

Low-Density Lipoprotein (LDL) cholesterol is one of the main target for cardiovascular (CV) prevention and therapy. In the last years, Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9-i) has emerged as a key therapeutic target to lower LDL and were introduced for prevention of CV events. Recently (June 2022) the Italian Medicines Agency (AIFA) modified the eligibility criteria for the use of PCSK9-i. We designed an observational study to estimate the prevalence of eligible subjects and evaluate the effectiveness of PCSK9-i applying a Target Trial Emulation (TTE) approach based on Electronic Health Records (EHR). Subjects meeting the eligibility criteria were identified from July 2017 (when PCSK9-i became available) to December 2020. Outcomes were all-cause death and the first hospitalization. Among eligible subjects, we identified those treated at date of the first prescription. Inverse Probability of Treatment Weights (IPTW) were estimated including demographic and clinical covariates, history of treatment with statins and the month/year eligibility date. Competing risk models on weighted cohorts were used to derive the Average Treatment Effect (ATE) and the Conditional Average Treatment Effect (CATE) in subgroups of interest. Out of 1976 eligible subjects, 161 (8%) received treatment with PCSK9-i. Treated individuals were slightly younger, predominantly male, had more severe CV conditions, and were more often treated with statin compared to the untreated subjects. The latter exhibited a higher prevalence of non-CV comorbidities. A significant absolute and relative risk reduction of death and a lower relative risk for the first hospitalization was observed. The risk reduction for death was confirmed in CATE analysis. PCSk9-i were prescribed to a minority of eligible subjects. Within the TTE framework, the analysis confirmed the association between PCSK9-i and lower risk of events, aligning with findings from randomized clinical trials (RCTs). In our study, PCSK9-i provided protection specifically against all-cause death, expanding upon the evidence from RCTs that had primarily focused on composite CV outcomes.


Asunto(s)
Registros Electrónicos de Salud , Inhibidores de PCSK9 , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , LDL-Colesterol/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Resultado del Tratamiento , Proproteína Convertasa 9/metabolismo
15.
G Ital Cardiol (Rome) ; 25(8): 557-566, 2024 Aug.
Artículo en Italiano | MEDLINE | ID: mdl-39072594

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) has been for decades a nosological entity lacking specific therapy, with some even questioning its existence. Recently, targeted therapies have been introduced for specific, albeit rare, phenotypes such as Fabry disease, hypertrophic cardiomyopathy and amyloidosis. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally developed as anti-diabetic drugs, have fortuitously emerged as effective molecules in improving the prognosis for both patients with heart failure with reduced ejection fraction (HFrEF) and those with HFpEF, reducing heart failure exacerbations by almost a third. Although there are some epidemiological differences, depending on the country and the context analyzed, it is generally agreed that HFpEF is the most represented phenotype of heart failure, and its prevalence has been increasing in recent years due to the increase in life expectancy, improved diagnostic sensitivity and accuracy, and an exponential increase in risk factors such as diabetes, hypertension, renal failure, chronic obstructive pulmonary disease and obesity. These are often associated, turning out to be an epiphenomenon of a more complex cardio-nephro-metabolic disease. However, data and characteristics from major trials are not always aligned with the features and needs of these patients in real-world settings.The Cardiovascular Observatory of Friuli-Venezia Giulia is a powerful clinical governance tool that allows us to specifically characterize these patients, identifying and directing them towards the most appropriate diagnostic and therapeutic pathways, contributing significantly to improved prognosis and reduced expenditure paid by the National Health System.The use of SGLT2i in HFrEF patients is poised to match that of historic neurohormonal treatments, while, being the only class of drugs currently recommended by the international guidelines, they should even surpass them in HFpEF patients. However, given the high prevalence of HFpEF, it is unlikely for its treatment to be a prerogative of cardiologists alone. In this regard, it will be crucial in the near future to implement shared and integrated pathways with other medical specialists (internists, diabetologists, and nephrologists), and especially with general practitioners, who most frequently encounter these patients, to select the cases with greater complexity and potential for effective therapeutic intervention.


Asunto(s)
Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Pronóstico , Factores de Riesgo , Italia , Prevalencia
16.
Int J Cardiovasc Imaging ; 40(6): 1341-1351, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38676849

RESUMEN

PURPOSE: The difference between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an afterload-independent index of left ventricular (LV) contractility. We assessed the independent prognostic value of ΔESPVR index by dipyridamole stress-cardiovascular magnetic resonance (CMR) in patients with known/suspected coronary artery disease (CAD). METHODS: We considered 196 consecutive patients (62.74 ± 10.66 years, 49 females). Wall motion and perfusion abnormalities at rest and peak stress were analysed. Replacement myocardial fibrosis was detected by late gadolinium enhancement (LGE) technique. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson's method. RESULTS: A reduced ΔESPVR index (≤ 0.02 mmHg/mL/m2) was found in 88 (44.9%) patients and it was associated with a lower LV ejection fraction (EF) and with a higher frequency of abnormal stress CMR and myocardial fibrosis. During a mean follow-up of 53.17 ± 28.21 months, 50 (25.5%) cardiac events were recorded: 5 cardiac deaths, 17 revascularizations, one myocardial infarction, 23 hospitalisations for heart failure or unstable angina, and 4 ventricular arrhythmias. According to Cox regression analysis, diabetes, family history, LVEF, abnormal stress CMR, myocardial fibrosis, and reduced ΔESPVR were significant univariate prognosticators. In the multivariate analysis the independent predictors were ΔESPVR index ≤ 0.02 mmHg/mL/m2 (hazard ratio-HR = 2.58, P = 0.007), myocardial fibrosis (HR = 2.13, P = 0.036), and diabetes (HR = 2.33, P = 0.012). CONCLUSION: ΔESPVR index by stress-CMR was independently associated with cardiac outcomes in patients with known/suspected CAD, in addition to replacement myocardial fibrosis and diabetes. Thus, the assessment of ΔESPVR index may be included into the standard stress-CMR exam to further stratify the patients.


Asunto(s)
Enfermedad de la Arteria Coronaria , Fibrosis , Imagen por Resonancia Cinemagnética , Contracción Miocárdica , Valor Predictivo de las Pruebas , Volumen Sistólico , Vasodilatadores , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Anciano , Pronóstico , Factores de Tiempo , Factores de Riesgo , Dipiridamol , Miocardio/patología , Medios de Contraste , Imagen de Perfusión Miocárdica/métodos , Presión Arterial , Estudios Retrospectivos
17.
G Ital Cardiol (Rome) ; 25(8): 546-556, 2024 Aug.
Artículo en Italiano | MEDLINE | ID: mdl-39072593

RESUMEN

The consumption of energy drinks (ED) has become a growing public health issue, since potentially ED-related serious adverse cardiovascular events, including arrhythmias, myocardial infarction, cardiomyopathies, and sudden cardiac death, have been reported in recent years. The substances contained in ED include caffeine, taurine, sugars, B group vitamins and phyto-derivatives, which, especially if taken in large quantities and in a short amount of time, could cause serious side effects through various mechanisms of action, such as increased blood pressure and QT interval prolongation. Although there are still many open questions on ED that require further specific investigations, there is an urgent need for information and educational plans to the population, as well as for regulatory actions, particularly regarding transparency of substances and possible adverse effects.


Asunto(s)
Enfermedades Cardiovasculares , Bebidas Energéticas , Trastornos Relacionados con Sustancias , Humanos , Bebidas Energéticas/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Cafeína/efectos adversos , Cafeína/administración & dosificación , Taurina/efectos adversos , Factores de Riesgo de Enfermedad Cardiaca
18.
JACC Adv ; 3(3): 100832, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38938828

RESUMEN

Background: Patients with likely pathogenic/pathogenic desmoplakin (DSP) variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting. Objectives: The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with DSP likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (DSP-TFC+). Methods: DSP-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics. Results: Among 252 DSP-TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank P = 0.0239). History of nonsustained VT (aHR 2.097; P = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age (P = 0.723) nor male sex (P = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]). Conclusions: DSP-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in DSP-TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, DSP-TFC+ patients with nonsustained VT should be considered as high-risk.

19.
PLoS One ; 18(2): e0281878, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36809251

RESUMEN

Patients with type 2 diabetes mellitus (T2DM) have more than twice the risk of developing heart failure (HF) compared to patients without diabetes. The present study is aimed to build an artificial intelligence (AI) prognostic model that takes in account a large and heterogeneous set of clinical factors and investigates the risk of developing HF in diabetic patients. We carried out an electronic health records- (EHR-) based retrospective cohort study that included patients with cardiological clinical evaluation and no previous diagnosis of HF. Information consists of features extracted from clinical and administrative data obtained as part of routine medical care. The primary endpoint was diagnosis of HF (during out-of-hospital clinical examination or hospitalization). We developed two prognostic models using (1) elastic net regularization for Cox proportional hazard model (COX) and (2) a deep neural network survival method (PHNN), in which a neural network was used to represent a non-linear hazard function and explainability strategies are applied to estimate the influence of predictors on the risk function. Over a median follow-up of 65 months, 17.3% of the 10,614 patients developed HF. The PHNN model outperformed COX both in terms of discrimination (c-index 0.768 vs 0.734) and calibration (2-year integrated calibration index 0.008 vs 0.018). The AI approach led to the identification of 20 predictors of different domains (age, body mass index, echocardiographic and electrocardiographic features, laboratory measurements, comorbidities, therapies) whose relationship with the predicted risk correspond to known trends in the clinical practice. Our results suggest that prognostic models for HF in diabetic patients may improve using EHRs in combination with AI techniques for survival analysis, which provide high flexibility and better performance with respect to standard approaches.


Asunto(s)
Aprendizaje Profundo , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Humanos , Pronóstico , Registros Electrónicos de Salud , Estudios Retrospectivos , Inteligencia Artificial , Factores de Riesgo
20.
Eur J Heart Fail ; 25(5): 698-710, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36781199

RESUMEN

AIMS: To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index ≥30 kg/m2 ) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. CONCLUSION: Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk.


Asunto(s)
Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Suecia/epidemiología , Volumen Sistólico , Antagonistas de Receptores de Angiotensina , Antagonistas Adrenérgicos beta/uso terapéutico , Obesidad/complicaciones , Obesidad/epidemiología , Sistema de Registros
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