Search

Introduction and objectives: Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals. Methods: The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials. Results: Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1 612 851.54 up to EUR 6 587 360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data. Conclusions: In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals. Resumo: Introdução e objetivos: A insuficiência cardíaca (IC) é uma síndrome clínica associada a uma elevada morbidade, mortalidade e despesa com custos de saúde. A dapagliflozina demonstrou ser eficaz na redução do risco de morte e hospitalização em doentes com IC, independentemente da fração de ejeção do ventrículo esquerdo. Este artigo visa projetar o potencial impacto da dapagliflozina na redução dos custos relacionados com hospitalizações subsequentes por IC em hospitais portugueses. Métodos: Foi recolhido, e posteriormente analisado de forma agregada em clusters, o número total de hospitalizações por IC, hospitalizações subsequentes por IC e duração média de internamento dos doentes com diagnóstico primário de IC em seis hospitais portugueses, entre janeiro de 2019 e dezembro de 2021. Os custos relacionados com hospitalizações subsequentes por IC foram calculados de acordo com a legislação portuguesa e tendo em consideração três abordagens – conservadora, média e complexa. A projeção da redução de custos teve por base as reduções do risco relativo (RRR) de hospitalizações por IC (hIC) reportadas nos ensaios clínicos com dapagliflozina. Resultados: Considerando uma RRR de 26% do risco de hospitalização subsequente por IC, com base no valor reportado na análise agregada dos estudos DAPA-HF e DELIVER relativa à RRR de hIC, a nossa projeção indica que a utilização da dapagliflozina resulta numa redução de custos. De acordo com a nossa projeção a redução de custos oscila entre €1,612,851.54 e €6,587,360.09, entre 2019 e 2021, ao considerar todos os hospitais envolvidos e as diferentes abordagens metodológicas. A projeção aponta para um resultado similar tendo por base uma RRR de 24%, resultante da ponderação das subanálises de DAPA-HF e DELIVER, juntamente com dados epidemiológicos do estudo PORTHOS. Conclusões: Nesta projeção, a utilização de dapagliflozina, em todos os doentes hospitalizados por IC que sejam elegíveis, está associada a uma redução direta significativa nos custos hospitalares. Estes dados reforçam a ideia de que, para além da melhoria nos resultados de saúde relacionados com a IC, a dapagliflozina pode ter um impacto significativo nos hospitais portugueses ao nível dos custos de saúde.

Familial hypertrophic cardiomyopathy (HCM) stands as a predominant heart condition, characterised by left ventricle hypertrophy in the absence of any associated loading conditions, with affected individuals having an increased risk of developing heart failure and sudden cardiac death (SCD). Two induced pluripotent stem cell (iPSC) lines were derived from peripheral blood mononuclear cells obtained from two unrelated individuals with previously reported nonsense mutations in the MYBPC3 gene. The first individual is a 48-year-old male (F26) with the MYBPC3 c.1731G > A HCM mutation, whereas the second individual is a 43-year-old female (F82) carrying the MYBPC3 c.2670G > A HCM mutation. The generated iPSCs exhibit appropriate expression of pluripotency markers, trilineage differentiation capacity and a normal karyotype. This resource contributes to gaining deeper insights into the pathophysiological mechanisms that underlie HCM.

Introduction and objectives: Current epidemiological data on heart failure (HF) in Portugal derives from studies conducted two decades ago. The main aim of this study is to determine HF prevalence in the Portuguese population. Using current standards, this manuscript aims to describe the methodology and research protocol applied. Methods: The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) is a large, three-stage, population-based, nationwide, cross-sectional study. Community-dwelling citizens aged 50 years and older will be randomly selected via stratified multistage sampling. Eligible participants will be invited to attend a screening visit at a mobile clinic for HF symptom assessment, anthropomorphic assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, one-lead electrocardiogram (ECG) and a sociodemographic and health-related quality of life questionnaire (EQ-5D). All subjects with NT-proBNP ≥125 pg/mL or with a prior history of HF will undergo a diagnostic confirmatory assessment at the mobile clinic composed of a 12-lead ECG, comprehensive echocardiography, HF questionnaire (KCCQ) and blood sampling. To validate the screening procedure, a control group will undergo the same diagnostic assessment. Echocardiography results will be centrally validated, and HF diagnosis will be established according to the European Society of Cardiology HF guidelines. A random subsample of patients with an equivocal HF with preserved ejection fraction diagnosis based on the application of the Heart Failure Association preserved ejection fraction diagnostic algorithm will be invited to undergo an exercise echocardiography. Conclusions: Through the application of current standards, appropriate methodologies, and a strong research protocol, the PORTHOS study will determine the prevalence of HF in mainland Portugal and enable a comprehensive characterization of HF patients, leading to a better understanding of their clinical profile and health-related quality of life. Resumo: Introdução e objetivos: Os dados epidemiológicos atuais sobre insuficiência cardíaca (IC) em Portugal provêm de estudos realizados há mais de duas décadas. O objetivo principal deste estudo é determinar a prevalência da síndrome de IC na população portuguesa com 50 ou mais anos, sendo, especificamente, objetivo deste artigo descrever as abordagens metodológicas e o protocolo de investigação aplicados. Métodos: O Estudo de Prevalência de Insuficiência Cardíaca em Portugal (PORTHOS) é um estudo observacional transversal de grande dimensão, de base populacional, nacional, constituído por três fases. Serão selecionados aleatoriamente por amostragem estratificada multietapas cidadãos com 50 ou mais anos residentes na comunidade em Portugal. Os participantes elegíveis serão convidados a participar numa visita de triagem, que decorrerá numa clínica móvel, durante a qual serão submetidos a avaliação de sintomas de IC, avaliação antropomórfica, um teste de N-terminal pró-peptídeo natriurético tipo B (NT-proBNP), eletrocardiograma de 1 derivação, questionários sociodemográficos e questionário de qualidade de vida relacionada à saúde (EQ-5D). Todos os participantes com NT-proBNP ≥125 pg/mL ou história prévia de IC serão submetidos a uma avaliação diagnóstica confirmatória composta por eletrocardiograma de 12 derivações, ecocardiografia completa, questionário de IC (KCCQ) e colheita de sangue. Para validar o procedimento de triagem, um grupo controlo passará pela mesma avaliação diagnóstica. Os resultados dos ecocardiogramas realizados serão validados centralmente e o diagnóstico de IC será confirmado de acordo com as recomendações de IC da Sociedade Europeia de Cardiologia. Uma subamostra aleatória de participantes com diagnóstico questionável de IC com fração de ejeção preservada (ICFEp), após a aplicação do algoritmo de diagnóstico de fração de ejeção preservada da Heart Failure Association (HFA-PEFF) será convidada a realizar ecocardiografia de esforço. Conclusão: Através da aplicação das recomendações atuais e abordagens metodológicas adequadas, o estudo PORTHOS irá determinar a prevalência da IC em Portugal Continental e permitir uma caracterização abrangente dos doentes com IC, para melhor compreensão do seu perfil clínico e qualidade de vida relacionada com a saúde.

Abstract Aims Multiple prediction score models have been validated to predict major adverse events in patients with heart failure. However, these scores do not include variables related to the type of follow‐up. This study aimed to evaluate the impact of a protocol‐based follow‐up programme of patients with heart failure regarding scores accuracy for predicting hospitalizations and mortality occurring during the first year after hospital discharge. Methods and results Data from two heart failure populations were collected: one composed of patients included in a protocol‐based follow‐up programme after an index hospitalization for acute heart failure and a second one—the control group—composed of patients not included in a multidisciplinary HF management programme after discharge. For each patient, the risk of hospitalization and/or mortality within a period of 12 months after discharge was calculated using four different scores: BCN Bio‐HF Calculator, COACH Risk Engine, MAGGIC Risk Calculator, and Seattle Heart Failure Model. The accuracy of each score was established using the area under the receiver operating characteristic curve (AUC), calibration graphs, and discordance calculation. AUC comparison was established by the DeLong method. The protocol‐based follow‐up programme group included 56 patients, and the control group, 106 patients, with no significant differences between groups (median age: 67 years vs. 68.4 years; male sex: 58% vs. 55%; median ejection fraction: 28.2% vs. 30.5%; functional class II: 60.7% vs. 56.2%, I: 30.4% vs. 31.9%; P = not significant). Hospitalization and mortality rates were significantly lower in the protocol‐based follow‐up programme group (21.4% vs. 54.7%; P

Familial hypertrophic cardiomyopathy (HCM) is the most common inherited heart condition. HCM patients show left ventricle hypertrophy without any associated loading conditions, being at risk for heart failure and sudden cardiac death. Two induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells obtained from two unrelated individuals, a 54-year-old male (F81) and a 44-year-old female (F93), both carrying the MYBPC3 c.1484G>A HCM mutation. iPSCs show expression of pluripotency markers, trilineage differentiation capacity and a normal karyotype. This resource enables further assessment of the pathophysiological development of HCM.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal condition that requires early diagnosis, management, and specific treatment. The availability of new disease-modifying therapies has made successful treatment a reality. Transthyretin amyloid cardiomyopathy can be either age-related (wild-type form) or caused by mutations in the TTR gene (genetic, hereditary forms). It is a systemic disease, and while the genetic forms may exhibit a variety of symptoms, a predominant cardiac phenotype is often present. This document aims to provide an overview of ATTR-CM amyloidosis focusing on cardiac involvement, which is the most critical factor for prognosis. It will discuss the available tools for early diagnosis and patient management, given that specific treatments are more effective in the early stages of the disease, and will highlight the importance of a multidisciplinary approach and of specialized amyloidosis centres. To accomplish these goals, the World Heart Federation assembled a panel of 18 expert clinicians specialized in TTR amyloidosis from 13 countries, along with a representative from the Amyloidosis Alliance, a patient advocacy group. This document is based on a review of published literature, expert opinions, registries data, patients’ perspectives, treatment options, and ongoing developments, as well as the progress made possible via the existence of centres of excellence. From the patients’ perspective, increasing disease awareness is crucial to achieving an early and accurate diagnosis. Patients also seek to receive care at specialized amyloidosis centres and be fully informed about their treatment and prognosis.

Introduction and objectives: Chronic heart failure (CHF) is a growing public health concern and diagnosis can be challenging, particularly in primary care. This study aims to estimate the budgetary impact of introducing N-terminal pro-B-type natriuretic peptide (NT-proBNP) for CHF diagnosis in a primary care setting from the perspective of the Portuguese health system. Methods: A budget impact analysis was conducted over one-year from the patients’ first presentation. The standard of care (SoC) was compared to NT-proBNP at the point-of-care (PoC) or laboratory (Lab). A decision tree model was used to estimate the downstream costs associated with each of the three pathways. Results: An estimated 81 012 patients were expected to present to primary care with new onset CHF symptoms. The use of NT-proBNP as a primary diagnostic tool is estimated to generate annualized savings of EUR 935 657 and EUR 2 982 443 in the Lab and PoC setting, respectively. Estimated cost savings were due to the need for fewer medical visits, hospitalizations and echocardiograms (ECHO). The Lab and PoC settings led to similar reductions in hospitalizations (14.4%) and ECHO (27%), but the reduction in medical visits was higher in the PoC setting (38% compared to 2.5%), resulting in higher savings compared to Lab. Conclusions: Using NT-proBNP for CHF diagnosis in primary care could result in considerable costs savings for the public health system in Portugal. This evidence might support health policy makers to reconsider the resource management and define a new strategy to mitigate the impact of CHF. Resumo: Introdução e objetivos: A insuficiência cardíaca crónica (ICC) é um problema de saúde pública crescente, mas o diagnóstico continua desafiante, nomeadamente nos cuidados de saúde primários. O objetivo deste estudo é avaliar e quantificar o impacto orçamental para o Serviço Nacional de Saúde (SNS) da introdução do NT-Probnp nos Cuidados de Saúde Primários para o diagnóstico de ICC. Métodos: Foi efetuada uma análise de impacto orçamental para estimar a potencial economia de custos da utilização do NT-Probnp na avaliação inicial do doente com sintomas sugestivos de ICC, com o horizonte de um ano. Foram comparados três braços: cuidado padrão (cp) sem NT-Probnp; a utilização do biomarcador em point-of-care (poc) ou laboratório (lab). Foi usado um modelo de árvore de decisão para estimar os custos associados a cada um dos cenários. Resultados: Foi estimado um total de 81 012 doentes com apresentação sugestiva de ICC. A utilização do NT-Probnp como meio diagnóstico primário pela medicina geral e familiar mostrou-se economizadora de custos, seja efetuado em lab ou POC, gerando uma economia anual estimada de 935.657€ e 2.982.443€, respetivamente. A economização de custos é devida à redução de consultas médicas, internamentos e ecografia (eco). A utilização de NT-Probnp em lab ou poc gera reduções idênticas em internamentos (14,4%) e eco (27%), mas a redução de consultas médicas é superior em poc (38% comparado com 2,5%), justificando a maior economia de custos neste contexto. Conclusão: A utilização de NT-probnp no diagnóstico de ICC nos Cuidados de Saúde Primários pode resultar numa redução de custos considerável para o SNS. Esta evidência pode suportar os decisores de política de saúde a reconsiderar a gestão de recursos e a definir uma nova estratégia para mitigar o impacto da doença.

Heart failure (HF) with reduced ejection fraction (HFrEF) is associated with high rates of hospitalization and death. It also has a negative impact on patients’ functional capacity and quality of life, as well as on healthcare costs. In recent years, new HFrEF prognosis-modifying drugs have emerged, leading to intense debate within the international scientific community toward a paradigm shift for the management of HFrEF. In this article, we report the contribution of a Portuguese HF expert panel to the ongoing debate.Based on the most recently published clinical evidence, and the panel members’ clinical judgment, three key principles are highlighted: (i) sacubitril/valsartan should be preferred as first-line therapy for HFrEF, instead of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker; (ii) the four foundation HFrEF drugs are the angiotensin receptor/neprilysin inhibitor, beta-adrenergic blocking agents, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors, regardless of the presence of type-2 diabetes mellitus; (iii) these four HFrEF drug classes should be introduced over a short-term period of four to six weeks, guided by a safety protocol, followed by a dose up-titration period of 8 weeks. Resumo: A insuficiência cardíaca (IC) com fração de ejeção reduzida (ICFEr) está associada a níveis elevados de hospitalização e mortalidade. A ICFEr também tem um impacto negativo na capacidade funcional e na qualidade de vida dos doentes, bem como na despesa em saúde. Nos últimos anos, surgiram novos medicamentos modificadores do prognóstico da ICFEr, originando um intenso debate na comunidade científica internacional em relação a uma mudança de paradigma para o tratamento da ICFEr. Neste artigo, relatamos a contribuição de um painel de especialistas portugueses em IC para o debate em curso.Com base na evidência clínica publicada mais recentemente e no julgamento clínico dos membros do painel, três princípios-chave são destacados: (i) sacubitril/valsartan deve ser preferido como terapia de primeira linha para a ICFEr, em vez de um inibidor da enzima de conversão da angiotensina ou um bloqueador do recetor da angiotensina; (ii) os quatro medicamentos básicos para a ICFEr são o inibidor do recetor da angiotensina e da neprilisina, os agentes bloqueadores beta-adrenérgicos, os antagonistas do recetor mineralocorticoide e os inibidores do cotransportador sódio-glucose 2, independentemente da presença de diabetes mellitus tipo 2; (iii) essas quatro classes de medicamentos para a ICFEr devem ser rapidamente introduzidas num período curto de 4-6 semanas, seguindo um protocolo de segurança, e depois tituladas durante as oito semanas seguintes.

OBJECTIVES:. Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired. Although lipid metabolism is crucial for platelet function, little is known regarding platelet metabolic changes associated with CPB-dysfunction. Our aim is to explore possible contribution of metabolic perturbations for platelet dysfunction after cardiac surgery. DESIGN:. Prospective cohort study. SETTING:. Tertiary academic cardiothoracic-surgery ICU. PATIENTS:. Thirty-three patients submitted to elective surgical aortic valve replacement. INTERVENTIONS:. Samples from patients were collected at three time points (preoperative, 6- and 24-hr postoperative). Untargeted metabolic analysis using high-performance liquid chromatography-tandem mass spectrometry was performed to compare patients with significant postoperative bleeding with patients without hemorrhage. Principal component analyses, Wilcoxon matched-pairs signed-rank tests, adjusted to FDR, and pairwise comparison were used to identify pathways of interest. Enrichment and pathway metabolomic complemented the analyses. MEASUREMENTS AND MAIN RESULTS:. We identified a platelet-related signature based on an overrepresentation of changes in known fatty acid metabolism pathways involved in platelet function. We observed that arachidonic acid (AA) levels and other metabolites from the pathway were reduced at 6 and 24 hours, independently from antiagreggation therapy and platelet count. Concentrations of preoperative AA were inversely correlated with postoperative chest tube blood loss but were not correlated with platelet count in the preoperative, at 6 or at 24 hours. Patients with significant postoperative blood-loss had considerably lower values of AA and higher transfusion rates. Values of postoperative interleukin-6 were strongly correlated with AA variability. CONCLUSIONS AND RELEVANCE:. Our observations suggest that an inflammatory-related perturbation of AA metabolism is a signature of cardiac surgery with CPB and that preoperative levels of AA may be more relevant than platelet count to anticipate and prevent postoperative blood loss in patients submitted to cardiac surgery with CPB.

Background: Cognitive impairment, anxiety and depression are common in heart failure (HF) patients and its evolution is not fully understood. Objectives: To assess the cognitive status of HF patients over time, its relation to anxiety and depression, and its prognostic impact. Methods: Prospective, longitudinal, single center study including patients enrolled in a structured program for follow-up after hospital admission for HF decompensation. Cognitive function, anxiety/depression state, HF-related quality of life (QoL) were assessed before discharge and during follow-up (between 6th and 12th month) using Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS) and Kansas City Cardiomyopathy Questionnaire, respectively. HF related outcomes were all cause readmissions, HF readmissions and the composite endpoint of all-cause readmissions or death. Results: 43 patients included (67±11.3 years, 69% male); followed-up for 8.2±2.1 months. 25.6% had an abnormal MoCA score that remained stable during follow-up (22.6±4.2 vs. 22.2±5.5; p=NS). MoCA score

Abstract Aims Non‐invasive telemonitoring (TM) in patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF) may be useful in the early diagnosis of HF decompensation, allowing therapeutic optimization and avoiding re‐hospitalization. We describe a TM programme in this population and evaluate its effectiveness during a 12 month period. Methods and results We conducted a single‐centre study of patients discharged from hospital after decompensated HF, allocated into three groups: prospective TM programme, prospective HF protocol follow‐up programme (PFP) with no TM facilities, and retrospective propensity‐matched usual care (UC). TM effectiveness was assessed by all‐cause hospitalizations and mortality; HF‐related hospitalization (HFH), days lost to unplanned hospital admissions/death, functional capacity and quality of life (New York Heart Association, Kansas City Cardiomyopathy Questionnaire, 6 min walk test, and plasma N‐terminal pro‐brain natriuretic peptide) were also evaluated. A total of 125 patients were included [65.9 ± 11.9 years, 32% female, left ventricular ejection fraction 27% (21–32)]. TM was similar to PFP regarding effectiveness; TM reduced all‐cause hospitalization and mortality (HR 0.27; 95% CI 0.11–0.71; P

Introduction and Objectives: Renin-angiotensin-aldosterone system inhibitors (RAASi) are the cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF). RAASi optimization in real-life care is challenged by hyperkalemia, a potentially fatal adverse event, which can necessitate downtitration or discontinuation of RAASi and negatively impact survival in HFrEF. The literature on this problem is sparse. We performed a systematic review of studies on HFrEF to investigate the prevalence, incidence, and risk factors of hyperkalemia, RAASi prescription rates, frequency of RAASi downtitration or discontinuation due to hyperkalemia, and the potential negative effect of the latter on prognosis. Methods: We conducted a MEDLINE (PubMed) search including observational and interventional studies published between January 1987 and May 2018. Results: A total of 30 observational and 18 interventional studies were included in the review. The incidence of hyperkalemia reported was between 0% and 63% in observational studies and was between 0% and 30% in clinical trials. Risk factors for hyperkalemia included RAASi prescription, older age, diabetes, and chronic kidney disease. In real-life studies, RAASi were downtitrated or discontinued in 3-22% of HFrEF patients; hyperkalemia was the reported cause in 5% of cases. No reports were found on the impact on prognosis of RAASi downtitration or discontinuation due to hyperkalemia. Conclusions: Hyperkalemia and RAASi downtitration or discontinuation are frequent, particularly in real-life HFrEF studies. Further research is needed to clarify the role of RAASi downtitration or discontinuation due to hyperkalemia and to assess its long-term prognostic impact in HFrEF patients. Resumo: Introdução e objetivos: Os inibidores do sistema renina-angiotensina-aldosterona (iSRAA) constituem pedras basilares para o tratamento da insuficiência cardíaca com fração de ejeção reduzida (IC-FER). A otimização dos iSRAA é dificultada pela ocorrência de hipercalemia, que obriga à redução/interrupção do iSRAA, podendo impactar negativamente na sobrevivência dos doentes com IC-FER. Esta questão é raramente abordada na literatura. Métodos: Realizámos uma revisão sistemática dos estudos sobre doentes com IC-FER para investigar a prevalência, incidência e fatores de risco para hipercaliemia, frequência de utilização de iSRAA, frequência de redução/interrupção dos iSRAA por hipercaliemia e o possível impacto negativo da redução/interrupção dos iSRAA no prognóstico. A pesquisa foi feita na Medline (PubMed) incluindo estudos observacionais e interventivos publicados entre janeiro de 1987 e maio de 2018. Resultados: Foram incluídos 30 estudos observacionais e 18 interventivos. A frequência relatada de hipercalemia variou entre 0% e 63% em estudos observacionais e entre 0% e 30% em ensaios clínicos. Fatores de risco para hipercalemia incluíram uso de iSRAA, idade avançada, diabetes e doença renal crónica. Em estudos de vida real, os iSRAA foram interrompidos em 3% a 22% dos doentes com IC-FER, sendo a hipercalemia a causa em 5% destes casos. Não foram encontrados relatos do impacto prognóstico da redução/interrupção dos iSRAA devida à hipercalemia. Conclusões: A hipercaliemia e redução/interrupção dos iSRAA são frequentes, principalmente em estudos de vida real de IC-FER. Novos estudos serão necessários para esclarecer o papel da redução/interrupção dos iSRAA devida a hipercalemia e para avaliar o seu impacto prognóstico a longo prazo em doentes com IC-FER.

Introduction and objectives: Over the last decade, several studies have suggested that left ventricular endomyocardial biopsy is safer and has a higher diagnostic yield than transvenous right ventricular biopsy. In addition, recent publications indicate that the transradial approach is a feasible and safe alternative to the transfemoral approach for sampling the left ventricle. We report our initial experience with transradial endomyocardial biopsy with regards to feasibility, safety and usefulness. Methods: Single-center registry of consecutive patients undergoing intended transradial left endomyocardial biopsy. Clinical and technical data were collected prospectively, with a particular focus on success rate and complications. Results: Twenty-seven patients were screened for left ventricle biopsy. Twenty (25) were selected for an intended transradial approach (mean age 51±18 years old, 22 male). Success rate was 100% with no crossover to femoral approach. There were no major complications. Two patients experienced mild radial spasm. One of them also had a run of non-sustained ventricular tachycardia.Indication for biopsy was either myocarditis or cardiomyopathy of unknown etiology. The final diagnosis was acute lymphocytic myocarditis in five patients, chronic myocarditis in one patient, amyloid light-chain amyloidosis in four patients and transthyretin amyloidosis in six patients. Myocarditis was ruled out in eight patients and amyloidosis in one patient. Conclusions: Transradial left ventricle endomyocardial biopsy is a very safe and feasible method of sampling the myocardium for histopathological analysis, with a good diagnostic yield and clinically meaningful results in properly selected patients. Resumo: Introdução e objetivos: Durante a última década, vários estudos têm sugerido que a biópsia endomiocárdica ventricular esquerda é mais segura e de superior rentabilidade diagnóstica do que a do ventrículo direito. Adicionalmente, várias publicações recentes têm introduzido a abordagem transradial como uma alternativa exequível e segura à transfemoral, para amostrar o ventrículo esquerdo. O objetivo deste estudo é reportar a experiência inicial de um centro em biópsia endomiocárdica ventricular esquerda transradial, relativamente a exequibilidade, segurança e utilidade. Métodos: Registo unicêntrico de doentes consecutivos submetidos a biópsia endomiocárdica ventricular esquerda, com acesso de primeira intenção radial. Registaram-se os dados clínicos e técnicos, com particular foco na taxa de sucesso e complicações. Resultados: Foram submetidos a biópsia endomiocárdica ventricular esquerda 27 doentes, 25 dos quais pré-selecionados para acesso transradial (idade média 51±18, 22 homens). A taxa de sucesso foi de 100%. Não ocorreram complicações major, apenas espasmo radial em dois doentes, num dos quais se observou uma salva de taquicardia ventricular não mantida. A indicação foi miocardite ou miocardiopatia de etiologia a esclarecer. O diagnóstico final foi de miocardite aguda em cinco doentes, miocardite crónica em um doente, amiloidose AL em quatro doentes e ATTR em seis doentes. Excluiu-se miocardite em oito doentes e amiloidose em um doente. Conclusão: A biópsia endomiocárdica ventricular esquerda transradial demonstrou ser segura, exequível e de boa rentabilidade diagnóstica, com resultados clinicamente relevantes em doentes selecionados.

Coronavirus disease 19 (COVID-19) has rapidly expanded to a global pandemic, resulting in significant morbidity and mortality. Even though predictors of infection remain unclear, age and preexisting cardiovascular conditions have been clearly identified as predictors of adverse outcomes and higher fatality rates. Since the virus infects host cells through angiotensin-converting enzyme 2 receptors, a key player in the renin-angiotensin-aldosterone system, the interaction between the cardiovascular system and the progression of COVID-19 is nowadays a focus of huge interest. In this review, the authors analyze the available and very recent evidence on the risk factors and mechanisms of the most relevant cardiovascular complications associated with COVID-19, including acute cardiac injury, myocarditis, stress-cardiomyopathy, ischemic myocardial injury, cytokine release syndrome, thrombotic disease, cardiac arrhythmias, heart failure, and cardiogenic shock. Finally, we discuss the cardiovascular impact of the therapies under investigation for COVID-19 treatment.

Resumo: A hemofilia A é uma doença hereditária da coagulação caracterizada por uma deficiência de fator VIII (FVIII) e que, principalmente nas suas formas graves, está associada a um risco hemorrágico elevado. Com o aumento da esperança média de vida destes doentes, a prevalência de eventos coronários agudos tem aumentado, mas a experiência na abordagem destes permanece escassa. A estratégia de atuação nos eventos coronários agudos em doentes hemofílicos, como demonstrado no presente caso, representa um verdadeiro desafio, não só pela necessidade de terapêutica anti‐agregante plaquetária (a qual, sendo indispensável para prevenção de trombose de stent, aumenta o risco hemorrágico), como também pela inexistência de recomendações específicas relacionadas com a terapêutica substitutiva mais adequada e segura nestas situações. Os autores descrevem o caso de um homem de 48 anos, com angina instável e diagnóstico prévio de hemofilia A grave, submetido a intervenção coronária percutânea sob terapêutica com FVIII sem complicações hemorrágicas. Abstract: Hemophilia A is an inherited coagulation disease characterized by a factor VIII (FVIII) deficiency and is associated with high hemorrhagic risk, especially in its severe forms. As the average life expectancy of patients with hemophilia has increased, so has the prevalence of acute coronary events. There is however limited experience in dealing with them. The strategy of acting on acute coronary events in patients with hemophilia, as demonstrated in the present case, is a real challenge, not only due to the need for antiplatelet therapy (which is essential in the prevention of stent thrombosis, but increases hemorrhagic risk), but also due to the lack of specific recommendations related to the most adequate and safe replacement therapy in these situations. The authors describe the case of a 48‐year‐old man with unstable angina and a previous diagnosis of severe hemophilia A who underwent percutaneous coronary intervention under FVIII therapy without hemorrhagic complications.

Introduction: Heart failure is associated with high rates of readmission and mortality, and there is a need for measures to improve outcomes. This study aims to assess the impact of the implementation of a protocol-based follow-up program for heart failure patients on readmission and mortality rates and quality of life. Methods: A quasi-experimental study was performed, with a prospective registry of 50 consecutive patients discharged after hospitalization for acute heart failure. The study group was followed by a cardiologist at days 7-10 and the first, third, sixth and 12th month after discharge, with predefined procedures. The control group consisted of patients hospitalized for heart failure prior to implementation of the program and followed on a routine basis. Results: No significant differences were observed between the two groups regarding mean age (67.1±11.2 vs. 65.8±13.4 years, p=0.5), NYHA functional class (p=0.37), or median left ventricular ejection fraction (27% [19.8-35.3] vs. 29% [23.5-40]; p=0.23) at discharge. Mean follow-up after discharge was similar (11±5.3 vs. 10.9±5.5 months, p=0.81).The protocol-based follow-up program was associated with a significant reduction in all-cause readmission (26% vs. 60%, p=0.003), heart failure readmission (16% vs. 36%, p=0.032), and mortality (4% vs. 20%, p=0.044). In the study group there was a significant improvement in all quality of life measures (p

Renin-angiotensin-aldosterone system (RAAS) inhibitors are a cornerstone in the treatment of heart failure with reduced ejection fraction (HFrEF). Sacubitril/valsartan modulates the neurohormonal axis by inhibiting both angiotensin receptors and neprilysin, and improves neurohormonal balance more than blocking the RAAS alone.The PARADIGM-HF trial validated this new treatment option for patients with HFrEF. Sacubitril/valsartan was also more effective than enalapril in slowing disease progression by decreasing the risk of worsening heart failure requiring hospitalization or emergency admission and the need for intensified therapy, heart failure devices or cardiac transplantation. More than 70% of patients included in PARADIGM-HF were in NYHA class II, and overall, the results indicate that sacubitril/valsartan should be started in the earliest symptomatic stages of the disease.As PARADIGM-HF has excellent robustness for a cardiovascular trial, sacubitril/valsartan has been included as a new treatment option with a strong level of recommendation in the main international guidelines.This expert task force proposes a practical guide to the use of this new drug that has been endorsed by the Working Group on Heart Failure of the Portuguese Society of Cardiology. Resumo: Os inibidores do sistema renina-angiotensina-aldosterona são uma das pedras basilares no tratamento da insuficiência cardíaca com fração de ejeção reduzida. O sacubitril/valsartan promove a modulação neuro-hormonal, bloqueando os recetores da angiotensina e inibindo a neprilisina, e produz um maior equilíbrio neuro-hormonal, mais do que o bloqueio do sistema renina-angiotensina-aldosterona isoladamente. O estudo PARADIGM-HF validou essa nova opção para o tratamento de doentes com insuficiência cardíaca e fração de ejeção reduzida, em alternativa ao IECA/ARA.O sacubitril/valsartan demonstrou ser mais eficaz do que o enalapril em retardar a progressão da doença, diminuindo o risco de agravamento da insuficiência cardíaca através da diminuição da necessidade de hospitalização e da menor necessidade de intensificação terapêutica, dispositivos ou transplante cardíaco. Mais de 70% dos doentes incluídos no estudo PARADIGM-HF estavam em classe II da NYHA, suportando a utilização do sacubitril/valsartan precocemente após o início dos sintomas.Como o estudo PARADIGM-HF apresentou uma robustez sem precedentes para um estudo cardiovascular, o sacubitril/valsartan foi incluído como uma nova opção de tratamento nas Recomendações internacionais mais relevantes, com um elevado nível de evidência (I-B).Este grupo de peritos em Insuficiência Cardíaca vem propor uma orientação prática para a utilização deste novo fármaco, subscrita pelo Grupo de Estudos de Insuficiência Cardíaca da Sociedade Portuguesa de Cardiologia. Keywords: Sacubitril/valsartan, PARADIGM-HF, Practical guidance, Heart failure with reduced ejection fraction, Palavras-chave: Sacubitril/valsartan, PARADIGM-HF, Guia prático, Insuficiência cardíaca com fração de ejeção reduzida

Introduction: Valvular heart disease (VHD) is increasing worldwide, mostly because of aging. Percutaneous valve intervention is the preferred therapeutic option in high-risk patients. Objective: To characterize the profiles of patients with VHD admitted to the cardiology ward at a tertiary referral center. Methods: On the basis of ICD-9 codes for VHD, the discharge notes of 287 patients hospitalized over a 22-month period were reviewed and analyzed. One hundred characteristics were considered. Results: Median age was 74 (23-93) years, and 145 (51%) were male. The admissions were elective (for valve intervention) in 36%. Heart failure (HF) was the reason for urgent admissions in 29.3%. Multiple comorbidities were observed in 53% of patients. Etiology of VHD was degenerative in 68%, functional in 15.3% and rheumatic (predominantly in women and younger patients) in 8.7%. Aortic valve disease was present in 63% (aortic stenosis in 56%), and was associated with HF (p=0.004), atrial fibrillation (AF) (p=0.01), and left ventricular (LV) dilatation (p=0.003) or hypertrophy (p

Introduction: In adults, unexplained left ventricular hypertrophy is usually due to sarcomeric hypertrophic cardiomyopathy (HCM). Fabry disease (FD) is rare but may mimic sarcomeric HCM, and has an adverse prognosis in the absence of specific treatment. We aimed to assess cardiologists’ awareness of FD based on data from the Portuguese Registry of Hypertrophic Cardiomyopathy. Methods: A total of 811 index patients, aged 55 ± 16 years, 486 (59.9%) male, were included. Three groups were characterized: A – 128 patients, 74 (57.8%) male, with pathogenic or likely pathogenic mutation(s) in sarcomeric genes; B – 234 patients, 146 (62.4%) male, with negative genetic testing; and C – 449 patients, 266 (59.2%) male, no genetic testing performed. The groups were compared in terms of whether FD was excluded in the registry. Potential red flags for FD were also analyzed and compared between groups. Results: Patients in group A were younger and more frequently had familial HCM (A – 53.9% vs. B – 20.1% vs. C – 18.3%; p

Introduction: We report the results of the Portuguese Registry of Hypertrophic Cardiomyopathy, an initiative that reflects the current spectrum of cardiology centers throughout the territory of Portugal. Methods: A direct invitation to participate was sent to cardiology departments. Baseline and outcome data were collected. Results: A total of 29 centers participated and 1042 patients were recruited. Four centers recruited 49% of the patients, of whom 59% were male, and mean age at diagnosis was 53±16 years. Hypertrophic cardiomyopathy (HCM) was identified as familial in 33%. The major reason for diagnosis was symptoms (53%). HCM was obstructive in 35% of cases and genetic testing was performed in 51%. Invasive septal reduction therapy was offered to 8% (23% of obstructive patients). Most patients (84%) had an estimated five-year risk of sudden death of

Resumo: A determinação dos níveis séricos de peptídeos natriuréticos (porção aminoterminal do peptídeo natriurético tipo B–NT‐proBNP ou da porção carboxiterminal ‐ BNP) constituiu avanço científico com impacto clínico muito relevante no diagnóstico e na determinação prognóstica de doentes com insuficiência cardíaca (IC). São hoje um instrumento com valor reconhecido nesse contexto e diversos estudos sugerem o seu interesse na titulação da terapêutica desses doentes. Recentemente, com o conhecimento do valor terapêutico do uso de inibidores da neprilisina/antagonista dos recetores da angiotensina, o uso desses dois biomarcadores na IC carece de interpretação diversa. O uso desses fármacos associa‐se à redução dos níveis de NT‐proBNP mas a aumento dos níveis de BNP. Os autores neste artigo conciso reveem a interpretação e valorização dos níveis de peptídios natriuréticos à luz da evidência mais recente. Abstract: Assessment of serum levels of natriuretic peptides, especially the amino‐terminal portion (NT‐proBNP) and the carboxy‐terminal portion (BNP) of pro‐B‐type natriuretic peptide, has had a highly significant clinical impact on the diagnosis and prognostic stratification of patients with heart failure (HF). They are now an instrument with recognized value in this context and several studies have demonstrated their value in tailoring therapy for these patients. Following the recent advent of angiotensin receptor‐neprilysin inhibitors (ARNIs), there is a need to review how these two biomarkers are interpreted in HF. The use of ARNIs is associated with a reduction in NT‐proBNP but an increase in BNP levels. The authors of this concise article review the interpretation of natriuretic peptide levels in the light of the most recent evidence. Palavras‐chave: Insuficiência cardíaca, Peptídeos natriureticos, BNP, NT‐proBNP, Keywords: Heart failure, Natriuretic peptides, B‐type natriuretic peptide, NT‐proBNP

Resumo: A insuficiência cardíaca é uma síndrome com elevada prevalência, morbilidade e mortalidade, sendo, no entanto, pouco reconhecida junto dos cidadãos e decisores políticos. O presente documento foi elaborado por um conjunto de peritos constituído por médicos especialistas em cardiologia, medicina interna e medicina geral e familiar, e pretende expor detalhadamente o problema da insuficiência cardíaca em Portugal a vários níveis: peso da síndrome, diagnóstico, tratamento e acompanhamento dos doentes. Para tal, são identificados e discutidos em detalhe os diferentes aspetos inerentes ao manejo da síndrome durante o processo assistencial, nas várias fases da doença e que incluem doentes hospitalizados e em ambulatório. De modo a otimizar a assistência médica prestada a estes doentes, são apontadas diversas soluções e estratégias a curto, médio e longo prazo com potencial para melhorarem a articulação e utilização dos recursos disponíveis. Pretendeu‐se desta forma destacar estratégias que, não se traduzindo num modelo único de melhoria, poderão ser adaptadas às diferentes especificidades regionais, de modo a aumentar o reconhecimento e a atenção prestada à insuficiência cardíaca em Portugal. Abstract: Heart failure is a syndrome with high prevalence, morbidity and mortality, but awareness of the disease is poor among the general public and policy makers. This document, which was prepared by a group of experts consisting of cardiologists, internists and general practitioners, aims to set out in detail the problem of heart failure in Portugal at several levels: burden of the disease, diagnosis, treatment and monitoring. To this aim, different aspects of the management of the various stages of the disease are identified and discussed in detail, covering both outpatients and hospitalized patients. In order to optimize the medical care provided to these patients, various short‐, medium‐ and long‐term solutions and strategies are put forward that have the potential to improve the integration and use of available resources. The intention is to highlight strategies that are not based on a single model but can be adapted to different regional circumstances, in order to increase awareness and improve management of heart failure in Portugal. Palavras‐chave: Insuficiência cardíaca, Documento de consensos, Prevalência, Tratamento multidisciplinar integrado, Impacto socioeconómico, Keywords: Heart failure, Consensus statement, Prevalence, Integrated multidisciplinary treatment, Socioeconomic impact

Resumo: A hipercalcemia é uma causa conhecida de perturbações do ritmo cardíaco, contudo, a sua associação a arritmias ventriculares é rara. Os autores apresentam o caso clínico de um doente de 53 anos de idade, com cardiomiopatia dilatada de etiologia isquémica e etanólica, e grave compromisso da função sistólica global, portador de sistema de ressincronização cardíaca (CRT) com cardioversor desfibrilhador (CDI), admitido no serviço de urgência por tempestade arrítmica, com múltiplos choques de CDI apropriados, refratária a terapêutica antiarrítmica. Na investigação etiológica foi documentada hipercalcemia grave secundária a hiperparatiroidismo primário até então desconhecido. Somente após redução da calcemia se observou cessação dos episódios de taquicardia ventricular. Abstract: Hypercalcemia is a known cause of heart rhythm disorders, however its association with ventricular arrhythmias is rare. The authors present a case of a fifty‐three years old male patient with a ischemic and ethanolic dilated cardiomyopathy, and severely reduced ejection fraction, carrier of cardiac resynchronization therapy (CRT) with cardioverter defibrillator (ICD), admitted in the emergency department with an electrical storm, with multiple appropriated ICD shocks, refractory to antiarrhythmic therapy. In the etiological investigation was documented severe hypercalcemia secondary to primary hyperparathyroidism undiagnosed until then. Only after the serum calcium level reduction ventricular tachycardia was stopped. Palavras‐chave: Hiperparatiroidismo, Hipercalcemia, Taquicardia ventricular, Keywords: Hyperparathyroidism, Hypercalcemia, Ventricular tachycardia

The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy.In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Resumo: O gene LMNA codifica a lâmina A/C, com importante papel na manutenção da coesão nuclear e organização da cromatina. Mutações neste gene estão geralmente associadas a doenças denominadas laminopatias. As manifestações cardíacas primárias destas mutações são miocardiopatia dilatada e defeitos da condução intracardíaca. Algumas mutações, associadas a lipodistrofia, mas não cardiomiopatia, estão também associadas a alterações metabólicas, como diabetes ou dislipidemia grave. Assim, descrevemos um novo fenótipo associado a uma mutação no exão 11 do gene LMNA: miocardiopatia hipertrófica, bloqueio auriculoventricular, dislipidemia grave e diabetes.Apresentamos a situação clínica de uma doente de 64 anos de idade, com miocardiopatia hipertrófica e mutação patogénica identificada no exão 11 do gene LMNA (c.1718C>T, Ser573Leu). A doente apresentou-se com hipertrofia ventricular grave sintomática, obstrutiva, refratária à terapêutica médica. Foi submetida a ablação septal por álcool e, posteriormente, a miectomia cirúrgica. Foi também diagnosticada dislipidemia grave, diabetes e obesidade, cumprindo os critérios para síndrome metabólica. Não foi identificada nenhuma outra característica fenotípica associada a mutações no gene LMNA. A doente foi ainda submetida a terapêutica de ressincronização cardíaca após o desenvolvimento de bloqueio auriculoventricular completo, sem causa aparente, na presença de ligeiro compromisso da função sistólica ventricular.A correlação de mutações no gene LMNA com diferentes fenótipos é complexa e ainda não completamente compreendida, englobando um largo espectro de gravidade clínica. Keywords: Hypertrophic cardiomyopathy, Lamin A/C, LMNA gene, Dyslipidemia, Diabetes, Atrioventricular block, Palavras-chave: Miocardiopatia hipertrófica, Lâmina A/C, Gene LMNA, Dislipidemia, Diabetes, Bloqueio auriculoventricular

High throughput sequencing technologies have revolutionized the identification of mutations responsible for genetic diseases such as hypertrophic cardiomyopathy (HCM). However, approximately 50% of individuals with a clinical diagnosis of HCM have no causal mutation identified. This may be due to the presence of pathogenic mutations located deep within the introns, which are not detected by conventional sequencing analysis restricted to exons and exon-intron boundaries.The aim of this study was to develop a whole-gene sequencing strategy to prioritize deep intronic variants that may play a role in HCM pathogenesis.The full genomic DNA sequence of 26 genes previously associated with HCM was analysed in 16 unrelated patients. We identified likely pathogenic deep intronic variants in VCL, PRKAG2 and TTN genes. These variants, which are predicted to act through disruption of either splicing or transcription factor binding sites, are 3-fold more frequent in our cohort of probands than in normal European populations. Moreover, we found a patient that is compound heterozygous for a splice site mutation in MYBPC3 and the deep intronic VCL variant. Analysis of family members revealed that carriers of the MYBPC3 mutation alone do not manifest the disease, while family members that are compound heterozygous are clinically affected.This study provides a framework for scrutinizing variation along the complete intronic sequence of HCM-associated genes and prioritizing candidates for mechanistic and functional analysis. Our data suggest that deep intronic variation contributes to HCM phenotype.

Familial amyloid polyneuropathy type I (FAP type I) is a rare hereditary systemic amyloidosis caused by the Val30Met mutation in the transthyretin (TTR) gene. The clinical onset and spectrum are variable and depend on phenotypic heterogeneity. Cardiac complications (dysrhythmias and conduction disturbances, cardiomyopathy and dysautonomia) indicate a poor prognosis, even after liver transplantation. We report an atypical case of FAP type I, highlighting the severe cardiac involvement and its complications.Early diagnosis of amyloid heart disease is increasingly important in the context of several clinical trials of promising new and experimental drugs. Resumo: A polineuropatia amiloidótica familiar tipo-I (PAF tipo-I) é um tipo raro de amiloidose hereditária e sistémica causada pela mutação Val30Met no gene da transtirretina (TTR). O início das manifestações e o espectro clínico podem ser variáveis e dependem da heterogeneidade fenotípica. As complicações cardíacas (disritmias e perturbações da condução, miocardiopatia e disautonomia) ditam um prognóstico mais reservado, mesmo após transplante hepático. É descrito um caso clínico atípico de PAF tipo-I com ênfase no grave envolvimento cardíaco e nas suas complicações.O diagnóstico precoce de cardiopatia amiloidótica tem assumido relevância no âmbito de vários ensaios clínicos com fármacos experimentais promissores. Keywords: Familial amyloid polyneuropathy type I, Dysrhythmia, Conduction disturbances, Cardiomyopathy, Dysautonomia, Palavras-chave: Polineuropatia amiloidótica familiar tipo-I, Disritmia, Perturbações da condução, Miocardiopatia, Disautonomia

Resumo: A pericardite constritiva é uma entidade clínica rara que pode colocar problemas diagnósticos. O método padrão para a confirmação do seu diagnóstico é o cateterismo cardíaco, com análise das curvas de pressão intracavitárias, as quais estão elevadas e, em telediástole, são iguais em todas as cavidades. O seu perfil diastólico em ambos os ventrículos apresenta o clássico aspeto dip-plateau e a diferença entre as pressões telediastólicas ventriculares não deve exceder 3-5 mmHg. Infelizmente estes critérios clássicos nem sempre se verificam e, na verdade, a sensibilidade e a especificidade da igualização das pressões telediastólicas dos ventrículos é relativamente baixa e de valor limitado no doente individualmente considerado. Esta realidade evidencia a necessidade de utilizar as novas técnicas de imagem cardíaca, que podem tornar claro o que é duvidoso. O caso clínico aqui descrito é um bom exemplo. Abstract: Constrictive pericarditis is a rare clinical entity that can pose diagnostic problems. The gold standard for diagnosis is cardiac catheterization with analysis of intracavitary pressure curves, which are high and, in end-diastole, equal in all chambers. The diastolic profile in both ventricles presents the classic dip-and-plateau pattern and the difference between the diastolic pressures of both ventricles should not exceed 3-5 mmHg. Unfortunately, these traditional criteria are not always present and in fact the sensitivity and specificity of equalization of diastolic pressures are relatively low and of limited value in individual patients. This highlights the need to use new cardiac imaging techniques to resolve any doubts. The case described here is a good example. Palavras-chave: Pericardite constritiva, Diagnóstico, Imagem, Keywords: Constrictive pericarditis, Diagnosis, Imaging

Background: Sarcomeric hypertrophic cardiomyopathy has heterogeneous phenotypic expressions, of which sudden cardiac death is the most feared. A genetic diagnosis is essential to identify subjects at risk in each family. The spectrum of disease-causing mutations in the Portuguese population is unknown. Methods: Seventy-seven unrelated probands with hypertrophic cardiomyopathy were systematically screened for mutations by PCR and sequencing of five sarcomeric genes: MYBPC3, MYH7, TNNT2, TNNI3 and MYL2. Familial cosegregation analysis was performed in most patients. Results: Thirty-four different mutations were identified in 41 (53%) index patients, 71% with familial hypertrophic cardiomyopathy. The most frequently involved gene was MYBPC3 (66%) with 22 different mutations (8 novel) in 27 patients, followed by MYH7 (22%), TNNT2 (12%) and TNNI3 (2.6%). In three patients (7%), two mutations were found in MYBPC3 and/or MYH7. Additionally, 276 relatives were screened, leading to the identification of a mean of three other affected relatives for each pedigree with the familial form of the disease. Conclusions: Disease-associated mutations were identified mostly in familial hypertrophic cardiomyopathy, corroborating the idea that rarely studied genes may be implicated in sporadic forms. Private mutations are the rule, MYBPC3 being the most commonly involved gene. Mutations in MYBPC3 and MYH7 accounted for most cases of sarcomere-related disease. Multiple mutations in these genes may occur, which highlights the importance of screening both. The detection of novel mutations strongly suggests that all coding regions should be systematically screened. Genotyping in hypertrophic cardiomyopathy enables a more precise diagnosis of the disease, with implications for risk stratification and genetic counseling. Resumo: Introdução: A miocardiopatia hipertrófica sarcomérica (MH) tem expressão fenotípica heterogénea, sendo a morte súbita cardíaca a mais temida. O diagnóstico genético é fundamental para identificar os indivíduos em risco em cada família. O perfil genético da doença é desconhecido na população portuguesa. População e métodos: Estudaram-se geneticamente 77 doentes-índice com MH, não-relacionados, pesquisando-se, por PCR e sequenciação, mutações nos genes MYBPC3, MYH7, TNNT2, TNNI3 e MYL2. Efetuou-se análise de co-segregação familiar na maioria dos doentes. Resultados: Identificaram-se 34 mutações diferentes em 41 doentes-índice (53%), 71% com MH familiar. O gene mais frequentemente envolvido foi o MYBPC3 (66%), identificando-se 22 mutações diferentes (8 novas) em 27 doentes-índice. Seguiram-se os genes MYH7 (22%), TNNT2 (12%) e TNNI3 (2,6%). Em 3 doentes (7%) identificaram-se 2 mutações nos genes MYBPC3 e/ou MYH7. Estudaram-se também 276 familiares detetando-se, em média, mais 3 indivíduos em risco, em cada pedigree com MH familiar. Conclusões: Foram identificadas mutações associadas a MH maioritariamente na doença familiar, reforçando a ideia corrente de as formas esporádicas estarem associadas a genes raramente estudados. A maioria das mutações é privada de cada família. O gene MYBPC3 é o mais frequentemente afetado. As mutações neste gene e no gene MYH7 são responsáveis pela maioria das situações de MH. Podem existir mutações múltiplas nestes genes, sendo mandatório o seu rastreio. A identificação de mutações novas aconselha a rastrear sistematicamente todas as regiões codificadoras. O estudo genético na MH permite um diagnóstico mais preciso da doença, determinante para a estratificação do risco e para o aconselhamento genético. Keywords: Sarcomeric hypertrophic cardiomyopathy, Mutations, Sarcomeric genes, Prevalence, Risk stratification, Palavras-chave: Miocardiopatia hipertrófica sarcomérica, Mutações, Genes sarcoméricos, Prevalência, Estratificação do risco

Resumo: A miocardiopatia Takotsubo é uma situação reversível, caracterizada por disfunção sistólica transitória do ventrículo esquerdo, a qual mimetiza uma síndrome coronária aguda. Ocorre habitualmente após stress físico ou emocional, com predomínio em mulheres na pós-menopausa, apesar de também poder afetar faixas etárias mais jovens e o género masculino. Apresenta-se frequentemente com dor torácica ou dispneia, alterações eletrocardiográficas sugestivas de enfarte agudo do miocárdio e ligeira elevação das enzimas cardíacas. A angiografia coronária exclui doença arterial obstrutiva, constatando-se, imagiologicamente, acinesia apical ventricular, com hipercontratilidade basal «compensatória».Foram propostos vários mecanismos fisiopatológicos para a síndrome, como doença aterosclerótica oculta, espasmo multivasos ou disfunção microvascular. Contudo, a hipótese mais aceite atualmente é a existência de um excesso de catecolaminas que, por causar uma sobrecarga de cálcio nos miócitos cardíacos, leva a perturbação da contração e função ventriculares. O tratamento é essencialmente de suporte, com reversão espontânea e completa das alterações num intervalo de dias a semanas. Contudo, a ocorrência de complicações e algumas comorbilidades podem predizer um prognóstico menos benigno. Assim, dado que a síndrome Takotsubo ainda é desconhecida em muitos aspetos e face ao crescente número de casos descritos, fez-se uma revisão da literatura do conhecimento atual. Abstract: Takotsubo cardiomyopathy is a reversible condition, characterized by transient left ventricular systolic dysfunction, that mimics an acute coronary syndrome. It usually occurs after physical or emotional stress, predominantly in postmenopausal women, although it also can affect younger age groups and males. It often presents as chest pain or dyspnea with electrocardiographic changes and mild elevation of cardiac enzymes suggesting acute myocardial infarction. Coronary angiography excludes obstructive coronary disease, and imaging reveals ventricular apical akinesia and compensatory hypercontractility of the basal segments.Various pathophysiological mechanisms have been proposed for the syndrome, such as occult atherosclerotic disease, multivessel spasm and/or microvascular dysfunction. However, the most widely accepted hypothesis at present is an excess of catecholamines causing calcium overload in cardiac myocytes, leading to disruption of contraction and ventricular function. Treatment is essentially supportive, with spontaneous and complete reversal of the changes within days or weeks. However, the presence of complications and comorbidities may predict a more adverse prognosis. As much is still unknown about takotsubo cardiomyopathy and the number of reported cases is growing, we present a literature review. Palavras-chave: Miocardiopatia Takotsubo, Síndrome coronária aguda, Disfunção ventricular esquerda, Excesso catecolamínico, Keywords: Takotsubo cardiomyopathy, Acute coronary syndrome, Left ventricular dysfunction, Catecholamine excess

The prevalence, complexity, clinical importance, heterogeneity and unpredictability of inherited cardiovascular diseases make the development of inherited cardiovascular disease centers an inevitability, with the ultimate goal of reducing the morbidity and mortality associated with these conditions. An inherited cardiovascular disease center may be seen as a subunit of a cardiology department, with health professionals specializing in these types of disorders, organized to provide excellence in all related areas, including diagnosis, treatment, follow-up, prevention, risk stratification and prognosis. Among its objectives are the development of action protocols and the creation of databases that enable patients to be included in national and international research networks. To achieve these objectives these centers should include functional units of clinical and basic sciences, research, training and education, acting in harmony in a holistic approach to patients and their families. As most experience on inherited cardiovascular diseases is based on hypertrophic cardiomyopathy and on “hypertrophic cardiomyopathy centers”, these centers represent an excellent opportunity to learn how to set up inherited cardiovascular disease centers. European centers will differ from country to country, reflecting the heterogeneity of national health systems, but will share a common core, presented in this document. Though we are aware that this ambitious project is not at all easy and may be difficult to implement in its entirety – in fact we consider it a major step – our position is that all the efforts to achieve it are worthwhile, considering that the main goal will always be the well-being of those affected by these particular disorders. Resumo: A prevalência, complexidade, importância clínica, heterogeneidade e imprevisibilidade das doenças cardíacas heredofamiliares torna a criação de Unidades de Doenças Cardíacas Hereditárias uma inevitabilidade, cujo objectivo final é reduzir a morbilidade e a mortalidade relacionadas com estas patologias. Uma Unidade de Doenças Cardíacas Hereditárias é uma subunidade de um departamento de Cardiologia constituída por profissionais de saúde especializados neste tipo de doenças, organizado de forma a proporcionar a excelência em todos as suas áreas, incluindo diagnóstico, tratamento, seguimento, prevenção, estratificação de risco e determinação de prognóstico. Alguns dos seus objectivos são o desenvolvimento de protocolos de actuação e a criação de bases de dados que permitam a inclusão de doentes em registos e redes de investigação nacionais e internacionais. Para atingir estes objectivos estes centros devem integrar Unidades Funcionais (clínica, ciências básicas, investigação, treino e educação), actuando harmonicamente numa abordagem holística de doentes e suas famílias. Como grande parte do conhecimento referente às doenças cardíacas hereditárias se baseia na miocardiopatia hipertrófica e na experiência adquirida com os “centros de miocardiopatia hipertrófica”, estes representam um excelente modelo para aprender como criar e desenvolver as Unidades de Doenças Cardíacas Hereditárias. A nível Europeu, as características destas Unidades serão diferentes de um país para outro, reflectindo a heterogeneidade dos diferentes sistemas e serviços nacionais de saúde, compartilhando no entanto um core comum, apresentado neste documento. Embora conscientes de que este projecto é ambicioso e de que a sua concretização como um todo não será uma tarefa fácil, consideramos a aplicação e divulgação deste conceito a nível nacional e Europeu um passo de grande importância. Assim, a nossa posição é que todos os esforços para atingir esta meta valem a pena, considerando que o principal objectivo será sempre o bem-estar dos doentes afectados por estas patologias. Keywords: Inherited cardiovascular diseases, Inherited cardiovascular disease centers, Hypertrophic cardiomyopathy, Hypertrophic cardiomyopathy centers, Palavras-chave: Doenças cardíacas hereditárias, Unidades de doenças cardíacas hereditárias, Miocardiopatia hipertrófica, Centros de miocardiopatia hipertrófica

Lactobacillus pentosus DSM 16366, a strain originally isolated from olive fermentation, was used as a starter culture for “Azeiteira” the preparation of Spanish style green olives. Inoculum was added to the fermentors as a freezedried starter culture or as a culture in the nutritive media. Lactic acid fermentation induction produced a more rapid acidification of brines and reduced the survival period of Enterobacteriaceae compared with the uninoculated process. The best results were obtained using the nutritive media as a culture carrier rather than the freeze-dried starter.

Resumo: A cardiomiopatia de stress e o enfarte agudo do miocárdio são geralmente considerados diagnósticos mutuamente exclusivos. Neste artigo reportamos o caso de uma doente de 54 anos com um quadro clínico de angor inaugural em repouso, cujo ecocardiograma e ventriculografia eram típicos de cardiomiopatia de stress. Não obstante, a coronariografia revelou uma lesão coronária suboclusiva, verificou‐se elevação muito significativa de troponina e documentou‐se uma cicatriz de enfarte subendocárdico por ressonância magnética cardíaca. Este é um caso raro em que um enfarte agudo do miocárdio e uma cardiomiopatia de stress ocorreram simultaneamente, em que o primeiro poderá ter sido o stressor que despoletou o segundo, dada a ausência de outras causas identificáveis. Abstract: Stress cardiomyopathy and myocardial infarction are generally regarded as mutually exclusive diagnoses. We report the case of a 54‐year‐old woman who presented with acute chest pain. Her echocardiogram and ventriculography were typical of stress cardiomyopathy, but she had one subocclusive coronary lesion, a highly significant rise in troponin and a subendocardial myocardial infarction scar documented on cardiac magnetic resonance. This is a rare case of concomitant myocardial infarction and stress cardiomyopathy, in which the acute coronary syndrome itself may have been the stressor, given the absence of other identifiable causes. Palavras‐chave: Cardiomiopatia de stress, Síndrome Takotsubo, Enfarte agudo do miocárdio, Ressonância magnética cardíaca, Keywords: Stress cardiomyopathy, Takotsubo syndrome, Acute myocardial infarction, Cardiac magnetic resonance

The process of natural lactic fermentation of green olives is too long and usually associated with several types of olive deteriorations, mainly the »bloater spoilage«. The control of pH and salt level in brine, a practice mostly used in the olive industry, is not sufficient to avoid these problems. The main objective of this work is the control of the fermentationprocess in order to reduce the duration of the process and the olive spoilage incidence.Therefore, some Moroccan green olives were alkali-treated and brined at 5 % NaCl. The controlled fermentation was carried out by adjusting pH, by inoculation with Lactobacillus plantarum I159 and the addition of potassium sorbate (0.05 % brine). The results showed arapid development of lactic fermentation with a remarkable reduction in »bloater spoilage «, without affecting the organoleptic properties, colour and texture of the final product.

‘Galega' is the main Portuguese olive variety providing the greatest percentage of table olive production from homemade and industrial methods. In this work a better understanding of the fermentation involved in both methods is intended. Yeasts and lactic acid bacteria (LAB) constitute the microflora acting in olive fermentation, with Pichia membranaefaciens being the dominant yeast specie present throughout the process. LAB develop their activity mainly along the second fermentation stage where Lactobacillus plantarum and Lactobacillus pentosus were isolated and identified, as well as Leuconostoc mesenteroides and Pediococcus pentosaceus. Results of a chemical analysis have shown the effectiveness of both homemade and industrial fermentation methods. Nevertheless, the chemical composition of the brines from homemade samples was more similar than those from the industrial ones. Remarkable differences were found in the phenolic compound profile mainly on the final fermentation stage. The amount of volatile compounds has enhanced on the same phase in both methods and some differences were found between them. Sensorial analysis has shown the best results obtained through the homemade method.

Sarcomeric hypertrophic cardiomyopathy (HCM) is the most common genetic cause of unexplained left ventricular hypertrophy and has no specific treatment. Anderson-Fabry disease (AFD) is rare and usually multisystemic, but occasionally expresses clinically as a predominantly cardiac phenotype mimicking HCM. We describe an illustrative case of a patient followed regularly for 25 years with a diagnosis of familial HCM and no identified sarcomeric mutations. Next-generation sequencing analysis identified a novel pathogenic mutation in the GLA gene, leading to a diagnosis of previously unknown multisystemic AFD, with consequent implications for the patient's treatment and prognosis and familial screening. Resumo: A miocardiopatia hipertrófica sarcomérica é a causa genética mais comum da hipertrofia ventricular esquerda inexplicada e não tem tratamento específico. A doença de Anderson-Fabry é rara, geralmente multissistémica mas, ocasionalmente, pode expressar-se clinicamente com um fenótipo predominantemente cardíaco, imitando miocardiopatia hipertrófica. Os autores descrevem o caso ilustrativo de uma doente seguida regularmente durante 25 anos com o diagnóstico de miocardiopatia hipertrófica familiar, sem mutação sarcomérica identificada. A utilização da análise de sequenciação de nova geração identificou uma mutação patogénica nova no gene GLA, aclarando o diagnóstico oculto de doença de Anderson-Fabry multissistémica, com as consequentes implicações terapêuticas, prognósticas e na investigação familiar. Keywords: Hypertrophic cardiomyopathy, Anderson-Fabry disease, Next-generation sequencing, Palavras-chave: Miocardiopatia hipertrófica, Doença de Anderson-Fabry, Sequenciação de nova geração

Abstract Severe hypertriglyceridemia has been consistently associated with an increased risk of cardiovascular disease and other complications, namely acute pancreatitis. We report a case of a 64 year-old woman with hypertrophic cardiomyopathy and metabolic syndrome with triglyceride level of 3260 mg/dL. Plasma exchange was performed with simultaneous medical treatment to achieve a rapid and effective lowering of triglycerides in order to prevent clinical complications. After three plasmapheresis sessions a marked reduction in triglyceride and total cholesterol levels was observed. Several cases have shown the importance of plasmapheresis in the treatment of acute pancreatitis. We intend to demonstrate the applicability of this technique as primary prophylaxis in the presence of extremely high serum triglyceridemia levels.