Management of RAASi-associated hyperkalemia in patients with cardiovascular disease.

Renin-angiotensin-aldosterone system inhibitors (RAASi) reduce morbidity and mortality in heart failure (HF) with reduced ejection fraction in a dose-dependent manner. They also have a positive impact in other cardiovascular diseases (CVDs). However, RAASi may induce hyperkalemia, a potentially life-threatening disorder. This risk is further increased in those with concomitant chronic kidney disease, diabetes mellitus, and/or in patients with hypertension. Current treatment guidelines recommend maximal RAASi dosing to improve clinical outcomes; however, this is often limited by the development of hyperkalemia. When this occurs, current guidelines recommend RAASi down-titration/interruption, which, while improving short-term prognosis, is associated with a negative long-term prognostic impact. At present, the European Society of Cardiology suggests the consideration of novel potassium binders (patiromer and sodium zirconium cyclosilicate) for the management of RAASi-associated hyperkalemia. Both drugs can reduce serum potassium levels and prevent recurrent hyperkalemia. Additionally, patiromer showed enabling of RAASi optimization in high-risk patients. Nevertheless, precise recommendations on the use of these drugs are lacking. Building upon current HF guideline recommendations, a multidisciplinary expert panel convened to design an algorithm providing practical guidance on the use of novel potassium binders/patiromer in patients with HF and/or other CVD. As a result of that effort, we present an evidence-based treatment algorithm for the management of hyperkalemia with novel potassium binders/patiromer in patients with HF and/or other CVD receiving RAASi, including the necessary monitoring to avoid induction of hypokalemia. This algorithm aims to maintain or up-titrate RAASi to optimized doses, while maintaining normokalemia, improved clinical outcomes, and long-term prognosis.

Telehealth Opportunities in the COVID-19 Pandemic Early Days: What Happened, Did Not Happen, Should Have Happened, and Must Happen in the Near Future?

The objective of this communication is to offer a better understanding of the value of telemedicine in health care, particularly its role in creating opportunities for continuity of care to patients in a complex and novel setting as were the circumstances of the early COVID-19 pandemic times. Crisis time is also a time for opportunities. With regard to telehealth, all players (providers, staff, and patients) should be informed about its benefits and should also become familiar with the use of the various telehealth options and this will only be achieved through large information campaigns necessary enriched by local teaching and training programs in both public and private institutions. The final aim is to launch the debate and foster ideas useful throughout the pandemic. This article covers the experiences of physicians as well as health professionals in the Iberian Peninsula (Spain and Portugal), to provide a clearer idea of what has happened and how we can improve it with the possibilities provided by telemedicine, while at the same time to put in evidence that public health systems need to be rethought to provide solutions to situations such as that we are experiencing.

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

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

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.

The potential of the inodilator levosimendan in maintaining quality of life in advanced heart failure.

Maintaining adequate quality of life (QoL) is an important therapeutic objective for patients with advanced heart failure and, for some patients, may take precedence over prolonging life. Achieving good QoL in this context may involve aspects of patient care that lie outside the familiar limits of heart failure treatment. The inodilator levosimendan may be advantageous in this setting, not least because of its sustained duration of action, ascribed to a long-acting metabolite designated OR-1896. The possibility of using this drug in an outpatient setting is a notable practical advantage that avoids the need for patients to attend a clinic appointment. Intermittent therapy can be integrated into a wider system of outreach and patient monitoring. Practical considerations in the use of levosimendan as part of a palliative or end-of-life regimen focused on preserving QoL include the importance of starting therapy at low doses and avoiding bolus administration unless immediate effects are required and patients have adequate baseline arterial blood pressure.

Generation of induced pluripotent stem cells from an individual with early onset and severe hypertrophic cardiomyopathy linked to MYBPC3: c.772G > A mutation.

Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the MYPBC3 gene, which encodes the cardiac myosin-binding protein C (cMyBP-C). Most pathogenic variants in MYPBC3 are either nonsense mutations or result in frameshifts, suggesting that the primary disease mechanism involves reduced functional cMyBP-C protein levels within sarcomeres. However, a subset of MYPBC3 variants are missense mutations, and the molecular mechanisms underlying their pathogenicity remain elusive. Upon in vitro differentiation into cardiomyocytes, induced pluripotent stem cells (iPSCs) derived from HCM patients represent a valuable resource for disease modeling. In this study, we generated two iPSC lines from peripheral blood mononuclear cells (PBMCs) of a female with early onset and severe HCM linked to the MYBPC3: c.772G > A variant. Although this variant was initially classified as a missense mutation, recent studies indicate that it interferes with splicing and results in a frameshift. The generated iPSC lines exhibit a normal karyotype and display hallmark characteristics of pluripotency, including the ability to undergo trilineage differentiation. These novel iPSCs expand the existing repertoire of MYPBC3-mutated cell lines, broadening the spectrum of resources for exploring how diverse mutations induce HCM. They additionally offer a platform to study potential secondary genetic elements contributing to the pronounced disease severity observed in this individual.

Generation of induced pluripotent stem cell lines from two unrelated individuals with familial hypertrophic cardiomyopathy carrying MYBPC3 nonsense mutations.

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.

Generation of induced pluripotent stem cell lines from two unrelated individuals with familial hypertrophic cardiomyopathy carrying the MYBPC3 missense c.1484G>A mutation.

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.

Activated clotting time value as an independent predictor of postoperative bleeding and transfusion.

OBJECTIVES: Activated clotting time (ACT) is commonly used to monitor anticoagulation during cardiac surgeries. Final ACT values may be essential to predict postoperative bleeding and transfusions, although ideal values remain unknown. Our aim was to evaluate the utility of ACT as a predictor of postoperative bleeding and transfusion use. METHODS: Retrospective study (722 patients) submitted to surgery between July 2018-October 2021. We compared patients with final ACT < basal ACT and final ACT ≥ basal ACT and final ACT < 140 s with ≥140 s. Continuous variables were analysed with the Wilcoxon rank-sum test; categorical variables using Chi-square or Fisher's exact test. A linear mixed regression model was used to analyse bleeding in patients with final ACT < 140 and ≥140. Independent variables were analysed with binary logistic regression models to investigate their association with bleeding and transfusion. RESULTS: Patients with final ACT ≥ 140 s presented higher postoperative bleeding than final ACT < 140 s at 12 h (P = 0.006) and 24 h (**P = 0.004). Cardiopulmonary bypass (CPB) time [odds ratio (OR) 1.009, 1.002-1.015, 95% confidence interval (CI)] and masculine sex (OR 2.842,1.721-4.821, 95% CI) were significant predictors of bleeding. Patients with final ACT ≥ 140 s had higher risk of UT (OR 1.81, 1.13-2.89, 95% CI; P = 0.0104), compared to final ACT < 140 s. CPB time (OR 1.019,1.012-1.026, 95% CI) and final ACT (OR 1.021,1.010-1.032, 95% CI) were significant predictors of transfusion. Female sex was a predictor of use of transfusion, with a probability for use of 27.23% (21.84-33.39%, 95% CI) in elective surgeries, and 60.38% (37.65-79.36%, 95% CI) in urgent surgeries, higher than in males. CONCLUSIONS: Final ACT has a good predictive value for the use of transfusion. Final ACT ≥ 140 s correlates with higher risk of transfusion and increased bleeding. The risk of bleeding and transfusion is higher with longer periods of CPB. Males have a higher risk of bleeding, but females have a higher risk of transfusion.

Effectiveness and Safety of Sacubitril/Valsartan in Patients with Chronic Kidney Disease-A Real-World Experience.

BACKGROUND: data regarding the effectiveness and safety of sacubitril/valsartan in heart failure and reduced ejection fraction (HFrEF) patients with chronic kidney disease (CKD) are scarse. OBJECTIVE: to evaluate the effectiveness and safety of sacubitril/valsartan in HFrEF and CKD in a real-world population. METHODS: we included consecutive ambulatory HFrEF patients that initiated sacubitril/valsartan between February 2017 and October 2020, stratified by CKD (KDIGO stage 5 excluded). PRIMARY OUTCOMES: the incidence rate per 100 patient-years and the annualized length of stay (LOS) of acute decompensated HF hospitalizations (HFH). SECONDARY OUTCOMES: all-cause mortality, NYHA improvement, and titration of sacubitril/valsartan. RESULTS: We included 179 patients, 77 with CKD, those being older (72 ± 10 vs. 65 ± 12 years, p < 0.001), had higher NT-proBNP (4623 ± 5266 vs. 1901 ± 1835 pg/mL, p < 0.001), and high anaemia incidence (p < 0.001). After 19 ± 11 months, a significant reduction in HFH adjusted incidence rate (57.5% decrease in CKD vs. 74.6%, p = 0.261) was observed, with 5 days there was a reduction in annualized LOS in both groups (p = 0.319). NYHA improved similarly in both groups (p = 0.670). CKD patients presented non-significant higher all-cause mortality (HR = 2.405, 95%CI: [0.841; 6.879], p = 0.102). Both groups had similar sacubitril/valsartan maximum dose achievement and drug withdrawal. CONCLUSION: sacubitril/valsartan was effective on reducing HFH and LOS without affecting all-cause mortality in a CKD real-world population.

Endometriosis and cardiovascular disease: A systematic review and meta-analysis.

OBJECTIVES: Endometriosis is a benign, estrogen-dependent, chronic inflammatory disease and is the commonest cause of chronic pelvic pain in younger women. Cardiovascular disease is the main cause of death worldwide. Because the relationship between endometriosis and CV disease is not well established, we performed a systematic review of longitudinal studies that assessed the occurrence of cardiovascular events in women with endometriosis compared to those without endometriosis. STUDY DESIGN: Systematic review with meta-analysis of longitudinal cohort/nested case-control studies with endometriosis patients and controls. A search was conducted of the MEDLINE, CENTRAL, and Embase databases from inception to November 2022. Random-effects meta-analysis was performed to estimate pooled hazard ratios (HR) and 95 % confidence intervals (95%CI). MAIN OUTCOME MEASURE: Cardiovascular outcomes such as ischemic heart disease and cerebrovascular disease. RESULTS: Six cohort studies were included, with a total of 254,929 participants. Meta-analysis showed that endometriosis was associated with a significantly increased risk of ischemic heart disease (HR 1.50, 95%CI 1.37-1.65; I2 = 0 %) and cerebrovascular disease (HR 1.17, 95%CI 1.07-1.29; I2 = 0 %). The one study that examined the relationship between cardiovascular mortality and endometriosis found a decreased risk in women with endometriosis relative to women without endometriosis (HR 0.55 (95%CI 0.47-0.65)). CONCLUSIONS: Endometriosis is associated with a significantly increased risk of cardiovascular disease, namely ischemic heart disease and cerebrovascular disease. Further studies are required to determine if endometriosis and/or its treatments are risk factors (particularly for cardiovascular mortality), and whether preventive measures could reduce the burden of cardiovascular disease in women with endometriosis. Study protocol registered at PROSPERO: CRD42022298830.

Expert perspectives on strategic factors for the management and prevention of heart failure in Portugal.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) has significant morbidity and mortality, and its prevalence will continue to increase in the future. This unfavorable evolution requires reflection as well as recommendations and decisions based on expert critical and strategic appraisal. METHODS: In the Acceleration on Heart Failure Empowerment and Awareness - the Portuguese Challenge (ATHENA-PT) study, a range of strategic factors that represent the strengths, weaknesses, threats, and opportunities (SWOT) of HF in Portugal were established. These factors were assessed quantitatively by experts, to create a final SWOT matrix for the management and prevention of HF in Portugal and to outline recommendations. RESULTS: For HF management, the panel emphasized the following strategic recommendations: (i) reimbursement of natriuretic peptides testing in primary healthcare; (ii) reimbursement of Doppler assessment in echocardiographic studies and promotion of detailed information in reports; (iii) intervention to improve the prognosis of patients with HF with preserved ejection fraction; (iv) ensuring effective healthcare transition between hospital and ambulatory units, using checklists/protocols; and (v) reinforcement and commitment to the training of primary health physicians and to the cardiac rehabilitation of patients. For the prevention of HF, the following recommendations/proposals were proposed: (i) campaigns to raise awareness of cardiovascular disease risk factors; (ii) promotion of physical exercise and healthy eating; and (iii) avoidance of therapeutic inertia in the management of risk factors. CONCLUSIONS: The acknowledgment of various strategic factors and their prioritization by experts made it possible to create and reinforce a range of new strategic recommendations for the management and prevention of HF.

The value of multiparametric prediction scores in heart failure varies with the type of follow-up after discharge: a comparative analysis.

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 < 0.001 and 5.4% vs. 17.9%; P < 0.001, respectively). When applied to the control group, COACH Risk Engine and BCN Bio-HF Calculator had, respectively, good (AUC: 0.835) and reasonable (AUC: 0.712) accuracy to predict hospitalization. There was a significant reduction of COACH Risk Engine accuracy (AUC: 0.572; P = 0.011) and a non-significant accuracy reduction of BCN Bio-HF Calculator (AUC: 0.536; P = 0.1) when applied to the protocol-based follow-up programme group. All scores showed good accuracy to predict 1 year mortality (AUC: 0.863, 0.87, 0.818, and 0.82, respectively) when applied to the control group. However, when applied to the protocol-based follow-up programme group, a significant predictive accuracy reduction of COACH Risk Engine, BCN Bio-HF Calculator, and MAGGIC Risk Calculator (AUC: 0.366, 0.642, and 0.277, P < 0.001, 0.002, and <0.001, respectively) was observed. Seattle Heart Failure Model had non-significant reduction in its acuity (AUC: 0.597; P = 0.24). CONCLUSIONS: The accuracy of the aforementioned scores to predict major events in patients with heart failure is significantly reduced when they are applied to patients included in a multidisciplinary heart failure management programme.

World Heart Federation Consensus on Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM).

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.

Repurposing the ß3-Adrenergic Receptor Agonist Mirabegron in Patients With Structural Cardiac Disease: The Beta3-LVH Phase 2b Randomized Clinical Trial.

Importance: Left ventricular (LV) hypertrophy contributes to the onset and progression of heart failure (HF), particularly for patients with pre-HF (stage B) for whom no treatment has yet proven effective to prevent transition to overt HF (stage C). The ß3-adrenergic receptors (ß3ARs) may represent a new target, as their activation attenuates LV remodeling. Objective: To determine whether activation of ß3ARs by repurposing a ß3AR agonist, mirabegron, is safe and effective in preventing progression of LV hypertrophy and diastolic dysfunction among patients with pre- or mild HF. Design, Setting, and Participants: The Beta3-LVH prospective, triple-blind, placebo-controlled phase 2b randomized clinical trial enrolled patients between September 12, 2016, and February 26, 2021, with a follow-up of 12 months. The trial was conducted at 10 academic hospitals in 8 countries across Europe (Germany, Poland, France, Belgium, Italy, Portugal, Greece, and the UK). Patients aged 18 years or older with or without HF symptoms (maximum New York Heart Association class II) were screened for the presence of LV hypertrophy (increased LV mass index [LVMI] of ≥95 g/m2 for women or ≥115 g/m2 for men) or maximum wall thickness of 13 mm or greater using echocardiography. Data analysis was performed in August 2022. Intervention: Participants were randomly assigned (1:1) to mirabegron (50 mg/d) or placebo, stratified by the presence of atrial fibrillation and/or type 2 diabetes, for 12 months. Main Outcomes and Measures: The primary end points were LVMI determined using cardiac magnetic resonance imaging and LV diastolic function (early diastolic tissue Doppler velocity [E/e'] ratio assessed using Doppler echocardiography) at 12 months. Patients with at least 1 valid measurement of either primary end point were included in the primary analysis. Safety was assessed for all patients who received at least 1 dose of study medication. Results: Of the 380 patients screened, 296 were enrolled in the trial. There were 147 patients randomized to mirabegron (116 men [79%]; mean [SD] age, 64.0 [10.2] years) and 149 to placebo (112 men [75%]; mean [SD] age, 62.2 [10.9] years). All patients were included in the primary intention-to-treat analysis. At 12 months, the baseline and covariate-adjusted differences between groups included a 1.3-g/m2 increase in LVMI (95% CI, -0.15 to 2.74; P = .08) and a -0.15 decrease in E/e' (95% CI, -0.69 to 0.4; P = .60). A total of 213 adverse events (AEs) occurred in 82 mirabegron-treated patients (including 31 serious AEs in 19 patients) and 215 AEs occurred in 88 placebo-treated patients (including 30 serious AEs in 22 patients). No deaths occurred during the trial. Conclusions: In this study, mirabegron therapy had a neutral effect on LV mass or diastolic function over 12 months among patients who had structural heart disease with no or mild HF symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT02599480.

Portuguese Heart Failure Prevalence Observational Study (PORTHOS) rationale and design - A population-based study.

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.

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine. METHODOLOGY: In this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population. RESULTS: HRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations. CONCLUSIONS: HRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.

[The "broken heart syndrome": state of the art]. / Miocardiopatia Takotsubo: estado da arte.

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.

Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population.

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.

[Constrictive pericarditis - new methods in the diagnosis of an old disease: a case report]. / Pericardite constritiva - novos métodos no diagnóstico de uma velha doença: a propósito de um caso clínico.

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 3-5mmHg. 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.