Publications by authors named "Brenda Moura"

31 Publications

SGLT-2 inhibitors: A step forward in the treatment of heart failure with reduced ejection fraction.

Rev Port Cardiol (Engl Ed) 2021 May 31. Epub 2021 May 31.

CINTESIS - Centro de Investigação em Tecnologias e Serviços de Saúde, Porto, Portugal; Serviço de Cardiologia, Hospital das Forças Armadas - Pólo do Porto, Portugal.

Heart failure (HF) is a major health problem with a significant impact on morbidity, mortality, quality of life and healthcare costs. Despite the positive impact of disease-modifying therapies developed over the last four decades, HF mortality and hospitalization remain high. We aim at reviewing the evidence supporting the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors, as a novel strategy for HF with reduced ejection fraction (HFrEF) treatment. The consistent observation of a reduction in HF hospitalizations in type-2 diabetes cardiovascular safety trials EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS raised the hypothesis that SGLT-2 inhibitors could have an impact in HF treatment. This hypothesis was first confirmed in 2019 with the DAPA-HF publication showing that dapagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations and cardiovascular mortality. This was reinforced by the EMPEROR-Reduced publication in 2020 showing that empagliflozin on top of optimized HFrEF therapy, reduced HF-hospitalizations. Both studies established SGLT-2 inhibitors as a fourth pillar of HFrEF prognosis-modifying therapy, in addition to the gold standard triple neurohormonal modulation/blockade.
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http://dx.doi.org/10.1016/j.repc.2021.02.010DOI Listing
May 2021

Patient profiling in heart failure for tailoring medical therapy. A consensus document of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2021 Jun 20;23(6):872-881. Epub 2021 May 20.

Department Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naïve to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up-titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate (<60 bpm or >70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate (<30 or >30 mL/min/1.73 m ) or hyperkalaemia. The pre-discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline-directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next.
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http://dx.doi.org/10.1002/ejhf.2206DOI Listing
June 2021

The year in cardiovascular medicine 2020: heart failure and cardiomyopathies.

Eur Heart J 2021 02;42(6):657-670

Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehaa1061DOI Listing
February 2021

Heart Failure Association of the European Society of Cardiology update on sodium-glucose co-transporter 2 inhibitors in heart failure.

Eur J Heart Fail 2020 11 27;22(11):1984-1986. Epub 2020 Oct 27.

Centre for Heart Diseases, Faculty of Health Sciences, Wrocław Medical University, Wrocław, Poland.

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: • Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin are recommended for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk. • Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalization and cardiovascular death in symptomatic patients with HF and reduced ejection fraction already receiving guideline-directed medical therapy regardless of the presence of type 2 diabetes mellitus.
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http://dx.doi.org/10.1002/ejhf.2026DOI Listing
November 2020

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2021 01 20;23(1):157-174. Epub 2020 Oct 20.

Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.
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http://dx.doi.org/10.1002/ejhf.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048442PMC
January 2021

Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).

Eur J Heart Fail 2020 09 21;22(9):1504-1524. Epub 2020 Aug 21.

Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.
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http://dx.doi.org/10.1002/ejhf.1957DOI Listing
September 2020

Sodium-glucose co-transporter 2 inhibitors in heart failure: beyond glycaemic control. A position paper of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 09 5;22(9):1495-1503. Epub 2020 Aug 5.

Department of Internal Medicine, and Department of Research and Education, General Hospital Murska Sobota, Murska Sobota, Slovenia.

Heart failure (HF) is common and associated with a poor prognosis, despite advances in treatment. Over the last decade cardiovascular outcome trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus have demonstrated beneficial effects for three SGLT2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) in reducing hospitalisations for HF. More recently, dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in patients with chronic HF with reduced left ventricular ejection fraction, with or without type 2 diabetes mellitus. A number of additional trials in HF patients with reduced and/or preserved left ventricular ejection fraction are ongoing and/or about to be reported. The present position paper summarises recent clinical trial evidence and discusses the role of SGLT2 inhibitors in the treatment of HF, pending the results of ongoing trials in different populations of patients with HF.
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http://dx.doi.org/10.1002/ejhf.1954DOI Listing
September 2020

Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential.

Cardiovasc Drugs Ther 2020 06;34(3):419-436

Heart Failure Clinic, Hospital São Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new drug class designed to treat patients with type 2 diabetes (T2D). However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)-related events and cardiovascular mortality. These benefits appear to be independent of glycaemic control and have recently been demonstrated in the HF population with reduced ejection fraction (HFrEF), with or without T2D. This comprehensive, evidence-based review focuses on the published studies concerning HF outcomes with SGLT2i, discussing issues that may underlie the different results, along with the impact of these new drugs in clinical practice. The potential translational mechanisms behind SGLT2i cardio-renal benefits and the information that ongoing studies may add to the already existing body of evidence are also reviewed. Finally, we focus on practical management issues regarding SGLT2i use in association with other T2D and HFrEF common pharmacological therapies. Safety considerations are also highlighted. Considering the paradigm shift in T2D management, from a focus on glycaemic control to a broader approach on cardiovascular protection and event reduction, including the potential for wide SGLT2i implementation in HF patients, with or without T2D, we are facing a promising time for major changes in the global management of cardiovascular disease.
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http://dx.doi.org/10.1007/s10557-020-06973-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242490PMC
June 2020

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry.

Eur J Heart Fail 2020 08 1;22(8):1424-1437. Epub 2020 Apr 1.

Unit of Cardiology, Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.

Aims: Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes.

Methods And Results: We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25-80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363-419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12-2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96-1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33-1.07; P = 0.083) and cardiovascular mortality (HR 0.62, 95% CI 0.38-1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01-1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09-0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29-0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37-0.87; P = 0.008) were independently associated with successful decrease.

Conclusion: Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease.
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http://dx.doi.org/10.1002/ejhf.1796DOI Listing
August 2020

Sensory-Discriminative Three-Dimensional Body Pain Mobile App Measures Versus Traditional Pain Measurement With a Visual Analog Scale: Validation Study.

JMIR Mhealth Uhealth 2020 08 19;8(8):e17754. Epub 2020 Aug 19.

Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States.

Background: To quantify pain severity in patients and the efficacy treatments, researchers and clinicians apply tools such as the traditional visual analog scale (VAS) that leads to inaccurate interpretation of the main sensory pain.

Objective: This study aimed to validate the pain measurements of a neuroscience-based 3D body pain mobile app called GeoPain.

Methods: Patients with temporomandibular disorder (TMD) were assessed using GeoPain measures in comparison to VAS and positive and negative affect schedule (PANAS), pain and mood scales, respectively. Principal component analysis (PCA), scatter score analysis, Pearson methods, and effect size were used to determine the correlation between GeoPain and VAS measures.

Results: The PCA resulted in two main orthogonal components: first principal component (PC1) and second principal component (PC2). PC1 comprises a combination score of all GeoPain measures, which had a high internal consistency and clustered together in TMD pain. PC2 included VAS and PANAS. All loading coefficients for GeoPain measures in PC1 were above 0.70, with low loadings for VAS and PANAS. Meanwhile, PC2 was dominated by a VAS and PANAS coefficient >0.4. Repeated measure analysis revealed a strong correlation between the VAS and mood scores from PANAS over time, which might be related to the subjectivity of the VAS measure, whereas sensory-discriminative GeoPain measures, not VAS, demonstrated an association between chronicity and TMD pain in locations spread away from the most commonly reported area or pain epicenter (P=.01). Analysis using VAS did not detect an association at baseline between TMD and chronic pain. The long-term reliability (lag >1 day) was consistently high for the pain area and intensity number summation (PAINS) with lag autocorrelations averaging between 0.7 and 0.8, and greater than the autocorrelations for VAS averaging between 0.3 and 0.6. The combination of higher reliability for PAINS and its objectivity, displayed by the lack of association with PANAS as compared with VAS, indicated that PAINS has better sensitivity and reliability for measuring treatment effect over time for sensory-discriminative pain. The effect sizes for PAINS were larger than those for VAS, consequently requiring smaller sample sizes to assess the analgesic efficacy of treatment if PAINS was used versus VAS. The PAINS effect size was 0.51 SD for both facial sides and 0.60 SD for the right side versus 0.35 SD for VAS. Therefore, the sample size required to detect such effect sizes with 80% power would be n=125 per group for VAS, but as low as n=44 per group for PAINS, which is almost a third of the sample size needed by VAS.

Conclusions: GeoPain demonstrates precision and reliability as a 3D mobile interface for measuring and analyzing sensory-discriminative aspects of subregional pain in terms of its severity and response to treatment, without being influenced by mood variations from patients.
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http://dx.doi.org/10.2196/17754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468641PMC
August 2020

From left ventricular ejection fraction to cardiac hemodynamics: role of echocardiography in evaluating patients with heart failure.

Heart Fail Rev 2020 03;25(2):217-230

Cardiology Unit and LTTA Centre, University of Ferrara, Viale Aldo Moro 8, 44024 Cona, Ferrara, Italy.

In clinical practice heart failure (HF) patients are generally classified on the basis of left ventricular (LV) ejection fraction. This approach, however, has important limitations. According to the definition of HF as a clinical syndrome that results from any impairment of LV filling or ejection of blood, a more articulated hemodynamic categorization of HF patients taking into account both LV forward flow and filling pressure would be desirable. However, the reliability of hemodynamic measures using echocardiographic techniques, which are the most used in current clinical practice for evaluation of HF patients, needs to be clarified. The aim of this article, therefore, is to verify whether echocardiography has acceptable feasibility, accuracy and reproducibility for the noninvasive evaluation of LV hemodynamics. This evaluation is necessary to progress to a hemodynamic characterization of HF patients that would ultimately overcome the HF classification based on ejection fraction.
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http://dx.doi.org/10.1007/s10741-019-09826-wDOI Listing
March 2020

Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy.

Rev Port Cardiol (Engl Ed) 2019 Jun 11;38(6):441-447. Epub 2019 Jul 11.

Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Center for Research in Health Technologies and Services (Cintesis), Porto, Portugal; Department of Cardiology, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal.

Introduction And Objectives: Dilated cardiomyopathy (DCM) is a myocardial disease that can progress to a terminal stage, requiring heart transplantation. In this work we aim to contribute to knowledge of genetic variants in adult patients undergoing heart transplantation due to end-stage DCM, reporting the results obtained in our single-center tertiary hospital series using target next-generation sequencing (NGS).

Methods And Results: Genetic variants were screened in 15 genes, preselected based on variants previously identified in DCM patients. Thirteen unrelated patients were included, nine (69%) male, mean age at diagnosis 33±13 years, eight (62%) with familial DCM. Nine genetic variants were identified in six (46%) patients: five in LMNA, two in LBD3, one in TNNT2 and one in TCAP. These variants were new in most patients. The majority were classified as of uncertain significance. Two patients were double and triple heterozygotes in the LBD3 and LMNA genes, respectively.

Conclusion: Our results highlight the potential of NGS in the genetic characterization of DCM patients. LMNA is one of the most frequently mutated genes and should be included in all target gene assessments of end-stage DCM patients until more data are available.
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http://dx.doi.org/10.1016/j.repc.2019.02.006DOI Listing
June 2019

Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing?

Cardiol Res Pract 2019 24;2019:2743650. Epub 2019 Apr 24.

National Center for Data Collection in Cardiology, Rua de Olivença n° 11, 7° Piso, Sala 701, 3000-306 Coimbra, Portugal.

Background: Sudden cardiac death (SCD) risk stratification in dilated cardiomyopathy (DCM) has been based on left ventricular ejection fraction (LVEF), even though SCD may occur with LVEF > 35%. Family history of unexplained SCD, especially in the young, raises concern about potential inheritable risk factors. It remains largely unknown how genetic tests can be integrated into clinical practice, particularly in the selection of implantable cardioverter defibrillator (ICD) candidates. We aimed to assess the diagnostic yield of genetic testing in DCM patients with a class I recommendation for ICD implantation, based on current guidelines.

Methods: We included ambulatory stable adult patients with idiopathic or familial DCM with previously implanted ICD. Molecular analysis included 15 genes (, , , , , , , , , , , , , , and ) using next-generation sequencing.

Results: We evaluated 21 patients, 12 (57%) males and 9 (43%) with familial DCM, including 3 (14%) with a family history of premature unexplained SCD. Mean age at DCM diagnosis was 40 ± 2 years, and mean age at ICD implantation was 50 ± 12 years. LVEF was 27 ± 9%, and LV end-diastolic diameter was 65 ± 7 mm. Genetic variants were found in six (29%) patients, occurring in 5 genes: , , , , and . The majority were classified as variants of uncertain significance. Family history of SCD was present in both patients with variants.

Conclusion: In patients with DCM and ICD, genetic variants could be identified in a significant proportion of patients in several genes, highlighting the potential role of genetics in DCM SCD risk stratification.
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http://dx.doi.org/10.1155/2019/2743650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507268PMC
April 2019

Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2019 May 16;21(5):553-576. Epub 2019 Apr 16.

Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.
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http://dx.doi.org/10.1002/ejhf.1461DOI Listing
May 2019

Changes in the vibration sensitivity and pressure pain thresholds in patients with burning mouth syndrome.

PLoS One 2018 21;13(5):e0197834. Epub 2018 May 21.

Departamento de Patologia e Diagnóstico Oral, Faculdade de Odontologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Objective: To investigate the presence of changes in vibration detection and pressure pain threshold in patients with burning-mouth syndrome (BMS).

Design Of The Study: Case-control study. The sample was composed of 30 volunteers, 15 with BMS and 15 in the control group. The pressure-pain threshold (PPT) and vibration-detection threshold (VDT) were examined. The clinical evaluation was complemented with the McGill Pain Questionnaire (MPQ), Douleur Neuropathique 4 (DN4) and Beck Depression and Anxiety Inventories (BDI and BAI, respectively).

Results: BMS subjects showed a statistically significant higher PPT in the tongue (p = 0.002), right (p = 0.001) and left (p = 0.004) face, and a significant reduction of the VDT in the tongue (p = 0.013) and right face (p = 0.030). Significant differences were also found when comparing the PPT and the VDT of distinct anatomical areas. However, a significant interaction (group × location) was only for the PPT. BMS subjects also showed significantly higher levels of depression (p = 0.01), as measured by the BDI, compared to controls; and a significant inverse correlation between the VDT in the left face and anxiety levels was detected.

Conclusions: The study of somatosensory changes in BMS and its correlations with the clinical features as well as the levels of anxiety and depression expands current understanding of the neuropathic origin and the possible contribution of psychogenic factors related to this disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197834PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962090PMC
November 2018

Reward Circuitry Plasticity in Pain Perception and Modulation.

Front Pharmacol 2017 21;8:790. Epub 2017 Nov 21.

Headache and Orofacial Pain Effort, Department of Biologic and Materials Sciences, School of Dentistry, Center for Human Growth and Development, Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.

Although pain is a widely known phenomenon and an important clinical symptom that occurs in numerous diseases, its mechanisms are still barely understood. Owing to the scarce information concerning its pathophysiology, particularly what is involved in the transition from an acute state to a chronic condition, pain treatment is frequently unsatisfactory, therefore contributing to the amplification of the chronic pain burden. In fact, pain is an extremely complex experience that demands the recruitment of an intricate set of central nervous system components. This includes cortical and subcortical areas involved in interpretation of the general characteristics of noxious stimuli. It also comprises neural circuits that process the motivational-affective dimension of pain. Hence, the reward circuitry represents a vital element for pain experience and modulation. This review article focuses on the interpretation of the extensive data available connecting the major components of the reward circuitry to pain suffering, including the nucleus accumbens, ventral tegmental area, and the medial prefrontal cortex; with especial attention dedicated to the evaluation of neuroplastic changes affecting these structures found in chronic pain syndromes, such as migraine, trigeminal neuropathic pain, chronic back pain, and fibromyalgia.
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http://dx.doi.org/10.3389/fphar.2017.00790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702349PMC
November 2017

The role of biomarkers in dilated cardiomyopathy: Assessment of clinical severity and reverse remodeling.

Rev Port Cardiol 2017 Oct 6;36(10):709-716. Epub 2017 Oct 6.

Cardiology Department, Centro Hospitalar São João, Porto, Portugal; Porto Medical School, Porto, Portugal.

Introduction: Biomarkers in dilated cardiomyopathy (DCM) reflect various pathobiological processes, including neurohormonal activation, oxidative stress, matrix remodeling, myocyte injury and myocyte stretch. We assessed the role of biomarkers in clinical and echocardiographic parameters and in left ventricular (LV) reverse remodeling (LVRR).

Methods: In this prospective study of 50 DCM patients (28 men, aged 59±10 years) with LV ejection fraction (LVEF) <40%, LVRR was defined as an increase of >10 U in LVEF after optimal medical therapy.

Results: Baseline LVEF was 25.4±9.8% and LV end-diastolic diameter (LVEDD)/body surface area (BSA) was 34.2±4.5 mm/m. LVRR occurred in 34% of patients within 17.6±15.6 months. No correlation was found between B-type natriuretic peptide (BNP), 25-hydroxyvitamin D (25(OH)D), CA-125, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) [Lp(a)], noradrenaline, adrenaline, renin or aldosterone and LVRR. Patients in NYHA class III or IV, with pulmonary congestion or ankle edema, had higher CA-125, cystatin C, BNP and hs-CRP levels (p<0.05). CA-125 was correlated with BNP (r=0.61), hs-CRP (r=0.56) and uric acid (r=0.52) (all p=0.01). BNP correlated directly with LVEDD (r=0.49), LV volumes (r=0.51), pulmonary artery systolic pressure (PASP) (r=0.43) and E/e' (r=0.31), and was inversely correlated with LVEF (r=-0.50) and e' velocity (r=-0.32) (p<0.05). CA-125 was positively correlated with left atrial volume/BSA (r=0.46), E/A ratio (r=0.60) and PASP (r=0.49) (p<0.05).

Conclusions: No correlation was found between biomarkers and LVRR, but CA-125, BNP and hs-CRP were predictors of clinical severity and congestion. BNP correlated with parameters of systolic and diastolic dysfunction, while CA-125 correlated with measures of diastolic dysfunction.
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http://dx.doi.org/10.1016/j.repc.2017.02.015DOI Listing
October 2017

Keratocystic odontogenic tumor.

Rev Col Bras Cir 2016 Dec;43(6):466-471

Oral Surgery Service, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

Objective: to evaluate the frequency of keratocystic odontogenic tumor (KOT) in the Oral Surgery Service (OSS) of the University Hospital Clementino Fraga Filho of the Federal University of Rio de Janeiro (HUCFF / UFRJ), with respect to recurrence rate, gender, age of recurrence and location of the injury Methods: clinical records were reviewed and histopathological reports of KOT patients of the HUCFF/UFRJ between 2002 and 2012. Patients diagnosed with KOT were divided into two groups for the occurrence of relapse: positive (n=6) and negative (n=19) Results: regarding the location, there was a predilection for the mandible. In the average age of patients in the positive group was 40.5 and the negative group, 35.53. In the distribution by gender, positive group showed equal distribution, different from that observed in the negative group, which showed a predilection for males Conclusion: KOT was the second most frequent injury in our patients, recurrence was lower among males and had the jaw as most affected location.
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http://dx.doi.org/10.1590/0100-69912016006013DOI Listing
December 2016

Left ventricular reverse remodeling in dilated cardiomyopathy- maintained subclinical myocardial systolic and diastolic dysfunction.

Int J Cardiovasc Imaging 2017 May 24;33(5):605-613. Epub 2016 Dec 24.

Cardiology Department, Centro Hospitalar São João, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.

In idiopathic dilated cardiomyopathy (DCM), myocardial deformational parameters and their relationships remain incompletely characterized. We measured those parameters in patients with DCM, during left ventricular reverse remodeling (LVRR). Prospective study of 50 DCM patients (in sinus rhythm), with left ventricular ejection fraction (EF) <40%. LVRR was defined as an increase of ten units of EF and decrease of diastolic left ventricular diameter (LVDD) in the absence of resynchronization therapy. Performed morphological analysis, myocardial performance quantification (LV and RV Tei indexes) and LV averaged peak systolic longitudinal strain (SSR long) and circumferential strain (SSR circ). At baseline, mean EF was 25.4 ± 9.8%, LVDD was 62.4 ± 7.4 mm, LVDD/BSA of 34.2 ± 4.5 mm/m and 34% had MR grade >II/IV. LVRR occurred in 34% of patients within 17.6 ± 15.6 months and was associated with a reduced rate of death or heart failure hospitalization (5.9% vs. 33.3; p = 0.03). Patients with LVRR had a final EF of 48.9 ± 7.9% (Δ LV EF of 22.4%) and there was a significant decrease (p < 0.05) in: LVDD/BSA, LV systolic diameter/BSA, LV diastolic volume, LV systolic volume, LV mass; an increase (p < 0.05) in sphericity index. However, measures of diastolic function (LA volume/BSA, e'velocity and' E/e'ratio), final LV and RV Tei indexes were not significantly different from baseline. Additionally, final SSR circ and SSR long values were not different from basal. Patients who recovered EF >50% (n = 10), SSR circ and SSR long were inferior to normal. Improvement in EF occurred in one-third of DCM pts and was associated with a decrease of major cardiac events. There was an improvement of diastolic and systolic volumes and in sphericity index, confirming truly LV reverse reshaping. However, myocardial performance indexes, SSR long and SSR circ in reverse-remodeled DCM were still abnormal, suggesting a maintained myocardial systolic and diastolic dysfunction.
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http://dx.doi.org/10.1007/s10554-016-1042-6DOI Listing
May 2017

Prevalence, predictors and prognosis of ventricular reverse remodeling in idiopathic dilated cardiomyopathy.

Rev Port Cardiol 2016 May 23;35(5):253-60. Epub 2016 Apr 23.

Cardiology Department, Hospital de São João, Porto, Portugal.

Introduction: Cardiac remodeling is manifested as changes in size, shape and function of the heart. We studied the prevalence, prognosis and predictors of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM) after optimized medical therapy.

Methods: A total of 113 IDCM patients were followed for 7.1±5.6 years. LVRR was defined as an increase of 10 units in ejection fraction (EF) and decrease in left ventricular diastolic diameter (LVDD), in the absence of resynchronization therapy.

Results: Baseline EF was 27±8% and LVDD index was 37.1±6.3 mm/m(2). LVRR occurred in 34.5% within 22.6 months. Final EF was 47.5±10.1%, LVDD index was 30.2±3.9 mm/m(2). LVRR was associated with better NYHA class (I-II) and lower BNP (p<0.01) and all patients were alive. Univariate predictive factors of LVRR (p<0.05) were mild hypertension, atrial fibrillation, ventricular hypertrophy on ECG, absence of left bundle branch block, shorter QRS duration, higher hematocrit, lower LVDD index, higher peak oxygen uptake efficiency (VO2/log 10[VE]) and lower dVE/VCO2/VO2, treatment with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and use of maximal doses of ACEI/ARB and beta-blockers. Multivariate regression analysis showed that higher doses of ACEI/ARB (OR: 0.32, 95% CI 0.11-0.92) were independently associated with LVRR. Non-transmural late enhancement on cardiac MRI was not a predictor of LVRR.

Conclusions: LVRR occurred in one third of IDCM patients, especially in those with mild hypertension and with less advanced disease, who may have benefited from maximal drug titration.
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http://dx.doi.org/10.1016/j.repc.2015.11.014DOI Listing
May 2016

Iron deficiency status irrespective of anemia: a predictor of unfavorable outcome in chronic heart failure patients.

Cardiology 2014 7;128(4):320-6. Epub 2014 Jun 7.

Cardiology Department, Centro Hospitalar de S. João, Porto, Portugal.

Objective: To assess the prognostic significance of iron deficiency (ID) in a chronic heart failure (CHF) outpatient population.

Methods And Results: We prospectively evaluated 127 patients with stable CHF and left ventricular ejection fraction ≤45%. Clinical and analytical data as well as information regarding the occurrence of the composite endpoint of overall mortality and nonfatal cardiovascular events were assessed. Among the 127 patients enrolled [81% men, median age: 62 years (25th-75th percentile: 53-68)], 46 (36%) patients had ID. Women, patients with higher plasma brain natriuretic peptide levels (>400 pg/ml) and with right ventricular systolic dysfunction presented ID more frequently (p < 0.05 for all). At 225 ± 139 days of follow-up, the composite endpoint occurred in 15 (12%) patients. It was more frequent in ID (24 vs. 5%, p = 0.001) and anemic patients (25 vs. 8%, p = 0.014). In a Cox regression analysis, ID was associated with a higher likelihood of composite endpoint occurrence (HR 5.00, 95% CI 1.59-15.78, p = 0.006). In a multivariable analysis adjusted for clinical variables, including the presence of anemia, ID remained a significant predictor of the composite endpoint (HR 5.38, 95% CI 1.54-18.87, p = 0.009).

Conclusion: In a CHF outpatient population, ID carried a higher risk of unfavorable outcome, irrespectively of the presence of anemia.
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http://dx.doi.org/10.1159/000358377DOI Listing
February 2015

A randomized controlled clinical trial to evaluate blood pressure changes in patients undergoing extraction under local anesthesia with vasopressor use.

J Craniofac Surg 2014 May;25(3):1108-10

From the *Dentistry School, †Oral Surgery Department, Dentistry School, and ‡Statistics Department, Fluminense Federal University, Rio de Janeiro, Brazil.

The control of hypertensive patients' blood pressure and heart rate using vasoconstrictors during surgical procedures under anesthesia is still a major concern in everyday surgical practice. This clinical trial aimed to evaluate the variation of blood pressure and heart rate in nonhypertensive and controlled hypertensive voluntary subjects undergoing oral surgery under local anesthesia with lidocaine hydrochloride and epinephrine at 1:100,000 (Alphacaine; DFL, Brazil), performed in the Oral Surgery Department, Dentistry School, Fluminense Federal University. In total, 25 voluntary subjects were divided into 2 groups: nonhypertensive (n = 15) and controlled hypertensives (n = 10). Blood pressure and heart rate were measured at 4 different times: T0, in the waiting room; T1, after placement of the surgical drapes; T2, 10 minutes after anesthesia injection; and T3, at the end of the surgical procedure. A statistically significant difference (P < 0.05) between the groups was found at times T0 and T2 for the systolic pressure but only at time T0 for the diastolic pressure. The assessment of the heart rate of both groups showed a statistically significant difference (P < 0.05) at time T1. An analysis of the employed anesthetic volume indicated no statistically significant difference (P > 0.05) between the amount administered to nonhypertensive and hypertensive subjects. It was concluded that the local anesthetics studied could safely be used in controlled hypertensive and nonhypertensive patients in compliance with the maximum recommended doses.
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http://dx.doi.org/10.1097/SCS.0000000000000736DOI Listing
May 2014

[Heart failure with preserved ejection fraction: A moving target].

Authors:
Brenda Moura

Rev Port Cardiol 2013 Sep 6;32(9):653-5. Epub 2013 Sep 6.

Serviço de Cardiologia, Hospital Regional Militar n.° 1, Porto, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.repc.2013.07.004DOI Listing
September 2013

Organization of heart failure management in European Society of Cardiology member countries: survey of the Heart Failure Association of the European Society of Cardiology in collaboration with the Heart Failure National Societies/Working Groups.

Eur J Heart Fail 2013 Sep 19;15(9):947-59. Epub 2013 Jun 19.

Department of Cardiology, Clinical Center of Serbia and Belgrade University School of Medicine, Serbia.

Aims: The aim of this document was to obtain a real-life contemporary analysis of the demographics and heart failure (HF) statistics, as well as the organization and major activities of the Heart Failure National Societies (HFNS) in European Society of Cardiology (ESC) member countries.

Methods And Results: Data from 33 countries were collected from HFNS presidents/representatives during the first Heart Failure Association HFNS Summit (Belgrade, Serbia, 29 October 2011). Data on incidence and/or prevalence of HF were available for 22 countries, and the prevalence of HF ranged between 1% and 3%. In five European and one non-European ESC country, heart transplantation was reported as not available. Natriuretic peptides and echocardiography are routinely applied in the management of acute HF in the median of 80% and 90% of centres, respectively. Eastern European and Mediterranean countries have lower availability of natriuretic peptide testing for acute HF patients, compared with other European countries. Almost all countries have organizations dealing specifically with HF. HFNS societies for HF patients exist in only 12, while in 16 countries HF patient education programmes are active. Most HFNS reported that no national HF registry exists in their country. Fifteen HFNS produced national HF guidelines, while 19 have translated the ESC HF guidelines. Most HFNS (n = 23) participated in the organization of the European HF Awareness Day.

Conclusion: This document demonstrated significant heterogeneity in the organization of HF management, and activities of the national HF working groups/associations. High availability of natriuretic peptide and echocardiographic measurements was revealed, with differences between developed countries and countries in transition.
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http://dx.doi.org/10.1093/eurjhf/hft092DOI Listing
September 2013

[Anemia and prognosis in acute coronary syndromes].

Authors:
Brenda Moura

Rev Port Cardiol 2012 Feb 9;31(2):133-4. Epub 2012 Jan 9.

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http://dx.doi.org/10.1016/j.repc.2011.12.003DOI Listing
February 2012

Congenital complete atrioventricular block and dilated cardiomyopathy: new light for an old disease.

Case Rep Cardiol 2012 2;2012:451375. Epub 2012 Aug 2.

Cardiology Department, Centro Hospitalar São João, 4200-319 Porto, Portugal.

We present a case of a patient with known complete congenital atrioventricular block (CAVB) since the age of 7 years old that developed dilated cardiomyopathy ten years after VVI-R pacemaker implantation. He presented severe biventricular dysfunction and was symptomatic despite optimal medical therapy. Cardiac resynchronization therapy was used, and he showed clinical and electrocardiographic improvement a month later.
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http://dx.doi.org/10.1155/2012/451375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008351PMC
May 2014

Survival of patients with familial dilated cardiomyopathy on optimal heart failure therapy.

Rev Port Cardiol 2009 Mar;28(3):263-8

Serviço de Cardiologia, Hospital de São João, Porto, Portugal.

Background: Familial dilated cardiomyopathy (FDCM) is characterized by clinical and genetic heterogeneity. There are still few survival studies concerning this subgroup of patients.

Aim: To determine the prognosis of patients with FDCM on optimal medical therapy and attending a heart failure clinic.

Methods: This is a prospective study including patients with FDCM, defined according to the guidelines of the European Society of Cardiology. Cardiovascular morbidity and all-cause mortality were evaluated.

Results: Thirty-six patients, 23 (64%) men, were followed for 3.8 +/- 2.5 years. Age at baseline was 42 +/- 14 years and 67% were in NYHA class II. In 22% heart failure symptoms first occurred after a respiratory infection, and in 6%, after pregnancy/delivery. Most patients were in sinus rhythm (89%) and 33% had left bundle branch block (LBBB). Baseline left ventricular (LV) ejection fraction was 28 +/- 9%, LV end-diastolic diameter was 68 +/- 8 mm and left atrial dimension was 46 +/- 9 mm. Baseline serum sodium was 140 +/- 3 mEq/l. All patients were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), 81% beta-blockers and 47% spironolactone. During follow-up, 5 patients died, 4 underwent heart transplantation and one received an implantable cardioverter-defibrillator. Five-year survival was 68%.

Conclusions: Five-year survival of our patients with FDCM, under optimal medical therapy, was similar to that of other forms of nonischemic DCM reported in the literature.
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March 2009

I-123-MIBG cardiac uptake imaging, in familial dilated cardiomyopathy.

Rev Port Cardiol 2009 Jan;28(1):29-36

Faculdade de Medicina do Porto, Serviço de Cardiologia, Hospital de São João, Porto, Portugal.

Unlabelled: The pathological significance of myocardial adrenergic activity in patients with heart failure is well documented. No previous study has assessed the usefulness of I123-metaiodobenzylguanidine (123I-MIBG) cardiac uptake imaging for the evaluation of familial dilated cardiomyopathy (DCM).

Objective: To evaluate cardiac adrenergic activity, using 123I-MIBG cardiac uptake imaging, in members of a genotyped family with DCM.

Methods: Clinical evaluation, 12-lead ECG, 2D echocardiogram, heart rate variability analysis by 24h Holter, plasma B-type natriuretic peptide (BNP) measurements and 123I-MIBG cardiac imaging were performed in all participants. Anterior projection planar images and single photon emission computed tomographies of the thorax were obtained 20 min and 4 hours after the intravenous administration of 370 MBq of 123I-MIBG (early and late images). Heart/mediastinal (H/M) ratio and myocardial washout (MW) rate were obtained based on the anterior planar images. In polar maps, segmental uptake of 123I-MIBG was evaluated using a 4-grade visual score: grade 1 - uptake > 75% of maximum myocardial uptake (MMU); grade 2 - uptake 51-75% of MMU; grade 3 - uptake 26-50% of MMU; grade 4 - uptake < or = 25% of MMU.

Results: Eleven adults were included: 4 with DCM, 4 with isolated left ventricular enlargement (LVE), and 3 with normal echocardiogram. Patients with DCM and LVE presented higher MW rates, lower H/M ratios and higher visual score grades than those with normal 2D echocardiograms. One patient with a normal echocardiogram but carrying the disease locus also presented an abnormal MIBG cardiac scintigram.

Conclusion: Patients with the phenotypic expression of the disease (DCM and LVE) and even carriers of the DCM gene with normal echocardiograms may present an abnormal MIBG cardiac scintigram, probably reflecting cardiac adrenergic hyperactivity. If confirmed in larger numbers, this method may be useful for the evaluation of DCM families.
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January 2009

Portuguese study of familial dilated cardiomyopathy: the FATIMA study.

Rev Port Cardiol 2008 Sep;27(9):1029-42

Serviço de Cardiologia-Hospital de São João, Faculdade de Medicina do Porto, Porto, Portugal.

Dilated cardiomyopathy (DCM) is a myocardial disease, characterized by ventricular dilatation and impaired systolic function, that in more than 30% of cases has a familial or genetic origin. Given its age-dependent penetrance, DCM frequently manifests in adults by signs or symptoms of heart failure, arrhythmias or sudden death. The predominant mode of inheritance is autosomal dominant, and in these cases mutations are identified in genes coding for cytoskeletal, sarcomeric or nuclear envelope proteins. To date, most studies aimed at molecular diagnosis of DCM have been in selected families, or in larger groups of patients, but screening for mutations in a limited number of genes. Consequently, the epidemiology of mutations in familial DCM remains unknown. There is thus a need for multicenter studies, involving screening for a wide range of mutations in several families and in cases of idiopathic DCM. The present article describes the methodology of a multicenter study, aimed at clinical and molecular characterization of familial DCM patients in the Portuguese population.
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September 2008
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