Cutaneous Markers of Cardiovascular Diseases.

Cardiovascular diseases are one of the most important global medical challenges because of their high rates of morbidity and mortality. In this narrative review, the authors address the most important dermatologic signs that can be present in patients with cardiovascular disease. The early recognition of these underestimated entities is very important as it may lead to an early diagnosis and timely treatment, thus lessening the effects of long-term disease and possibly improving the prognosis.

As doenças cardiovasculares são um dos desafios médicos mais importantes a nível mundial devido às suas elevadas taxas de morbilidade e mortalidade. Neste artigo, é feita uma revisão das manifestações cutâneas mais importantes que poderão estar presentes em doentes com doenças cardiovasculares. O reconhecimento atempado destas entidades clínicas é fulcral, uma vez que permite um diagnóstico e tratamento precoces, minimizando os efeitos destas doenças a longo prazo e possivelmente melhorando o prognóstico destes doentes.

Parámetros hematológicos descuidados en el pronóstico dela insuficiencia cardíaca-Evidencia del estudio REFERENCE / Neglected hematological parameters in heart failure prognosis – Disclosures from the REFERENCE study

Aims: In heart failure patients, anemia and iron deficiency are predictors of poor outcome. We studied the association of anemia, iron deficiency and relatedhematological parameters with short-term rehospitalization, short-term all-cause mortality and end of follow-up all-cause mortality in heart failure patients.Material and Methods: Anemia, iron deficiency, red cell distribution width and erythropoietin were assessed in patients hospitalized with acute decompensated heart failure.Univariate Cox proportional hazard model was used to assess the relationship between variables and outcomes.Results: 65 patients were followed for a median of 13.7 (Q1-Q3 6.7-18.9) months. Mean age was 79.2 (SD 10.8) years. The mean left ventricular ejectionfraction was 50.38 ± 19.07 %. Variables associated with an increased risk for short-term rehospitalization were red cell distribution width (HR 1.35; 95% CI 1.16-1.58), anemia (HR 3.81; 95% CI 1.29-11.28) and anemia with iron deficiency (HR 3.50; 95% CI 1.30-9.38). Increased risk for short-term mortality was associatedwith red cell distribution width (HR 1.83; 95% CI 1.29-2.59), erythropoietin (HR 1.38; 95% CI 1.04-1.82), absolute iron deficiency (HR 7.22; 95% CI 1.50-34.81)and anemia with iron deficiency (HR 4.48; 95% CI 1.26-15.88). Variables associated with increased risk for end of follow-up mortality were red cell distributionwidth (HR 1.31; 95% CI 1.12-1.54) and erythropoietin (HR 1.29; 95% CI 1.11-1.49).Conclusions: Conclusions: Anemia and red cell distribution width correlated with higher risk for short-term rehospitalization. Absolute iron deficiency, red celldistribution width and erythropoietin were associated with higher risk for short-term mortality. Red cell distribution width and erythropoietin were associatedwith higher risk for end of follow-up mortality. (AU)

Insuficiencia Cardíaca: una Enfermedad Maligna Conclusiones del Estudio REFERENCE / Heart Failure a Malignant Disease- Insights from the REFERENCE Study

Aims: Heart failure (HF) short-term prognosis persists poor. We studied the rate of short-term readmission due to HF, short-term all-cause mortality and end of follow-up all-cause mortality. Material and Methods: We assessed patients admitted with acuteHF in class III or IV of NYHA. Univariate Cox proportional hazard model was performed. Survival curves were plotted using the Kaplan-Meier method and compared with the log-rank test for readmission days post-discharge. Results: We followed 65 patients for a median of 13.7 (Q1-Q3 6.7-18.9) months. The 30-day post-discharge readmission rate was 13.8%, the 90-day post-discharge readmission percentage was 33.8% and year readmission rate 61.5%. The 30-day mortality rate was 10.8% and 90- day mortality was 18.5%. Year mortality rate was 36.9% and 40% of the patients were deceased by the end of the follow-up. Length of stay (LOS) correlated with short-term readmission in the general population (HR: 1.022, 95% CI: 1.009-1.036, P value<0.001) and in Heart Failure with Reduced Ejection Fraction patients (HFrEF) (HR: 1.029, 95% CI: 1.008-1.050, Pvalue=0.006). The number of hospitalizations correlated with short-term readmission in the general population (HR: 1.543, 95% CI: 1.224-1.945, P- value<0.001) and in the Heart Failure with Mid-Range Ejection Fraction subgroup (HFmrEF) (HR: 2.814, 95% CI: 1.075-7.365, P- value=0.035). In the Heart Failure with Preserved Ejection Fraction (HFpEF) subgroup both the LOS per specific admission (HR: 1.063, 95% CI: 1.006-1.123, P value=0.030) and the accumulated LOS for all admissions (HR: 1.051, 95% CI: 1.008-1.095, P value=0.019) were associated with end of followup mortality... (AU)

Introducción: La insuficiencia cardíaca (IC) tiene un mal pronóstico a corto plazo. Estudiamos las tasas de reingreso precoz por IC, mortalidad global precoz y mortalidad global al final del seguimiento. Material y métodos: Evaluamos a enfermos ingresados por IC descompensada en clase III o IV de la NYHA. Se utilizó el modelo de riesgo proporcional de Univariante Cox. Se aplicó el método de Kaplan-Meier para obtener curvas de supervivencia para dias de reingreso pós-alta e se comparó al log-rank test. Resultados: La mediana de seguimiento de los 65 enfermos fue de 13.7 (Q1-Q3 6.7-18.9) meses. La tasa de reingreso a los 30 días del alta fue del 13.8%, a los 90 días del alta fue del 33.8% y la tasa anual fue del 61.5%. La mortalidad a los 30 días del alta fue del 10.8% y del 18.5% a los 90 días. La mortalidad anual fue del 36.9% y al final del seguimiento del 40%. La duración del ingreso se correlacionó con el reingreso precoz en la población general (HR: 1.022, 95% CI: 1.009-1.036, P-value<0.001) y en el subgrupo con fracción de eyección reducida (HR: 1.029, 95% CI: 1.008-1050, P-value=0.006). El número de ingresos fue un marcador de mal pronóstico para el reingreso precoz en la población general (HR: 1.543, 95% CI: 1.224-1.945, P-value<0.001) y en el subgrupo con fracción de eyección intermedia (HR: 2.814, 95% CI: 1,075-7,365, P-value=0.035). En el subgrupo con fracción de eyección preservadala duración de ingreso por hospitalización... (AU)

Gal-3 y ST2 como biomarcadores: un paso al frente en el pronóstico de la Insuficiencia Cardíaca / Gal-3 and ST2 Biomarkers - A Step Forward in Heart Failure Prognostication

Aims: The American College of Cardiology (ACA)/ American Heart Association (AHA) granted Galectin-3 (Gal-3) and Suppression of Tumorigenicity 2 (ST2) evaluation a class II recommendation for HF prognosis, as an adjunctive to conventional clinical risk factors and natriuretic peptides dosing in 2013. However, in Europe this endorsement is not valid. The purpose of this study was to study the association of Gal-3 and ST2 collected at-admission with early (defined as the period of 90 days post-discharge) rehospitalization and overall mortality, and end of follow-up overall mortality in HF patients. Additionally, aminoterminal B-type natriuretic peptide (NT-proBNP) at admission was considered to test if a multi-marker strategy could yield supplementary information. Material and Methods: Gal-3, ST2 and NT-proBNP were assessed in patients hospitalized with acute decompensated HF in class III or IV of New York Heart Association (NYHA). Univariate Cox proportional hazard model was used to assess the relationship between variables and outcomes. Since there are no standardized cut-offs for Gal-3 and ST2, the multiclass Area Under the Curve Receiver-Operator Characteristic (AUCROC) as defined by Hand and Till was used to evaluate the overall performance of each biomarker as a predictor of the outcomes. Results: We followed 65 patients for a median of 13.7 (Q1-Q3 6.7-18.9) months. Gal-3 correlated with short-term rehospitalization (HR: 9.886, 95% CI: 2.027-48.214, P-value=0.005), short-term mortality (HR: 13.731, 95% CI: 1.650-114.276, P value=0.015) and end of follow-up mortality (HR: 4.492, 95% CI: 1.594-12.656, P-value=0.004). The association of elevated NT-proBNP determinations increased the risk of short-term rehospitalization (HR: 11.985, 95% CI: 1.962-73.218, P value=0.007) and end of follow-up mortality (HR: 78.025, 95% CI: 7.592-801.926, P-value<0.001). ST2 correlated with end of follow-up mortality (HR: 4.846, 95% CI: 1.396-16.825, P-value=0.013)... (AU)

Chagas cardiomyopathy and heart failure: From epidemiology to treatment.

Chagas disease is among the neglected tropical diseases recognized by the World Health Organization that have received insufficient attention from governments and health agencies. Chagas disease is endemic in 21 Latin America regions. Due to globalization and increased migration, it has crossed borders and reached other regions including North America and Europe. The clinical presentation of the disease is highly variable, from general symptoms to severe cardiac involvement that can culminate in heart failure. Chagas heart disease is multifactorial, and can include dilated cardiomyopathy, thromboembolic phenomena, and arrhythmias that may lead to sudden death. Diagnosis is by methods such as enzyme-linked immunosorbent assay (ELISA) and the degree of cardiac involvement should be investigated with complementary exams including ECG, chest radiography and electrophysiological study. There have been insufficient studies on which to base specific treatment for heart failure due to Chagas disease. Treatment should therefore be derived from guidelines for heart failure that are not specific for this disease. Heart transplantation is a viable option with satisfactory success rates that has improved survival.

Oral Anticoagulation in the Elderly: New Oral Anticoagulants-Innovative Solution for an Old Problem?

Direct oral anticoagulants emerge as the most innovative and promising drug toward preventing and treating cardiovascular disease, raising great interest among the scientific community. Numerous studies and meta-analysis generated much data clarifying clinicians' doubts; however, uncertainties remain regarding their use in particular groups such as patients with prosthetic valves, in valvular atrial fibrillation (defined as atrial fibrillation related to mitral rheumatic heart disease or prosthetic heart valves), among the elderly, in paraneoplastic thromboembolism, in pulmonary embolism with hemodynamic compromise, and scarcity of specific antidotes. This review article intends to condense the vast scientific production addressing new oral anticoagulants by focusing on their advantages and disadvantages when used on the elderly.

Iron deficiency in chronic and acute heart failure: A contemporary review on intertwined conditions.

Iron Deficiency (ID) is increasingly recognized as a prevalent comorbid condition in Heart Failure (HF). Despite this, the pathophysiological mechanisms for progressive ID in either chronic or acute HF are still poorly understood. Beyond the traditional factors for iron deficit in the general population, we ought to review the specificities of such paucity in the HF patient, particularly focusing on the interplay between heightened inflammation, overactivity of the sympathetic nervous system and the so-called cardio-renal-anaemia-ID syndrome. Currently, ID constitutes not only an independent prognostic marker but also a novel safe therapeutic target. Particularly, in selected stable HF patients with reduced left ventricular ejection fraction, intravenous (IV) iron improves symptomatic burden and reduces hospitalizations due to worsening HF. On this topic, the main trials of IV iron with either iron sucrose (Toblli et al., FERRIC-HF and IRON-HF) or ferric carboxymaltose (FAIR-HF, CONFIRM-HF and EFFECT-HF) will be summarized and discussed. Finally, we debate the gaps in knowledge of ID in special populations, namely the unreliability of routine plasmatic surrogate markers to assess iron status in acute and advanced HF, the challenging patient with both HF and Chronic Kidney Disease, as well as efficacy and safety concerns in these settings and the potential role of iron correction in cardiac resynchronization therapy candidates.

The Burden of Iron Deficiency in Heart Failure: Therapeutic Approach.

Heart failure (HF) is highlighted by its burdening symptom-limited exercise capacity and recurrent hospitalizations. Despite substantial advances regarding disease-modifying drugs in HF with reduced ejection fraction, additional therapeutic strategies to improve quality of life are invaluable. Currently, iron deficiency (ID) is overwhelmingly recognized in over 30% to 50% of patients with stable chronic HF, which worsens prognosis. The established pathophysiological mechanisms of progressive HF may be intertwined with increasing myocardial iron scarcity, wherein one begets the other. Most importantly, ID constitutes a novel target for symptom relief in carefully selected patients. In this regard, intravenous iron may be a safe and efficacious intervention, potentially reducing HF hospitalizations. We discuss the evidence and gaps in knowledge concerning iron therapy in HF and propose a practical, comprehensive, clinically oriented algorithm for timely adequate iron replenishment in different clinical scenarios. Finally, we further debate imperative decision-making before intervention and the drawbacks of such a strategy.

Mid-regional pro-adrenomedullin and ST2 in heart failure: Contributions to diagnosis and prognosis.

Heart failure has a high prevalence in developed countries. It is a frequent cause of hospital admission and has an important impact on morbidity, mortality and healthcare costs. Biomarkers have been widely studied in heart failure, as they improve diagnosis and prognostic assessment. Natriuretic peptides are already a part of daily clinical practice but several other biomarkers are being studied. This review focuses on mid-regional pro-adrenomedullin (MR-proADM) and ST2. Neither of these biomarkers is useful in the diagnosis of acute heart failure. However, both have considerable short- and long-term prognostic value in patients with acute and with stable chronic heart failure. The utility of these two biomarkers in guiding heart failure treatment is yet to be established. ST2 appears to have some advantages compared to MR-proADM, because it is more closely associated with ventricular remodeling and fibrosis.

Arrhythmogenic right ventricular dysplasia: Atypical clinical presentation. / Miocardiopatia arritmogénica do ventrículo direito ­ particularidades de um caso.

A 67-year-old man was admitted to our hospital after episodes of syncope preceded by malaise and diffuse neck and chest discomfort. No family history of cardiac disease was reported. Laboratory workup was within normal limits, including D-dimers, serum troponin I and arterial blood gases. The electrocardiogram showed sinus rhythm with T-wave inversion in leads V1 to V3. Computed tomography angiography to investigate pulmonary embolism showed no abnormal findings. Transthoracic echocardiography (TTE) displayed massive enlargement of the right ventricle with intact interatrial septum and no pulmonary hypertension. Cardiac magnetic resonance imaging (MRI) confirmed right ventricular (RV) dilatation and revealed marked hypokinesia/akinesia of the lateral wall. Exercise stress testing was negative for ischemia. According to the 2010 Task Force criteria for arrhythmogenic right ventricular dysplasia (ARVD), this patient presented two major criteria (global or regional dysfunction and structural alterations: by MRI, regional RV akinesia or dyskinesia or dyssynchronous RV contraction and RV ejection fraction ≤40%, and repolarization abnormalities: inverted T waves in right precordial leads [V1, V2, and V3]); and one minor criterion (>500 ventricular extrasystoles per 24 hours by Holter), and so a diagnosis of ARVD was made. After electrophysiologic study (EPS) the patient received an implantable cardioverter-defibrillator (ICD). This late clinical presentation of ARVD highlights the importance of TTE screening, possibly complemented by MRI. The associated risk of sudden death was assessed by EPS leading to the implantation of an ICD. Genetic association studies should be offered to the offspring of all ARVD patients.

Oral Antiplatelet Therapy in Coronary Disease.

Ischemic heart disease is the major isolated cause of death worldwide, responsible for 7,249,000 deaths in 2008, 12.7% of deaths from any causes. The inhibition of platelet activation and aggregation is an important therapeutic target. Cyclooxygenase inhibitors and thienopyridines are currently the 2 most used pharmacological classes, but novel antiplatelet agents have currently an important role. The most recent thienopyridine, prasugrel, allows an irreversible inhibition of the P2Y12 platelet receptor associated to a faster and more consistent onset of action rather the previous antiplatelet agents of the same class. Cyclopentyl-triazolo-pyrimidines, a newer pharmacological class from which ticagrelor is an example, also act at the P2Y12 platelet receptor, and like prasugrel, ticagrelor inhibits platelet aggregation in a fast and consistent manner, however, in a reversible way. This article aims to conduct a review on the literature about the most recent information and guidelines on oral antiplatelet agents available for the management of coronary disease.

Procalcitonin as Biomarker of Infection: Implications for Evaluation and Treatment.

Procalcitonin (PCT) is a quickly measurable marker, assumed to have high sensitivity and specificity for sepsis and infection. A literature search was conducted to evaluate PCT ability as a diagnostic and prognostic tool in infectious processes and its ability to monitor the antibiotic therapy. PCT level is increased in bacterial and fungal infections, but not in viral infections, with a significantly higher level in patients with bacteremia compared with uninfected patients (2.5 vs. 0.3 ng/mL; P < 0.0001). A PCT value of ≤0.1 ng/mL discards bacteremia and microbiological tests (negative predictive value of 96.3%), >0.1 ng/mL needs microbiological tests, and >1.0 ng/mL is indicative of bacteremia. Antibiotic treatment algorithms guided by PCT decreased the need for antibiotic treatment in approximately 50%. PCT is a promising test in clinical practice to decide the introduction of antibiotic therapy in addition to the existing tools, without neglecting the clinical assessment, with a significant decrease in costs.

Acute decompensated heart failure (ADHF): A comprehensive contemporary review on preventing early readmissions and postdischarge death.

Heart failure (HF) is an increasingly prevalent syndrome and a leading cause of both first hospitalization and readmissions. Strikingly, up to 25% of the patients are readmitted within 30 to 60-days, accounting for HF as the primary cause for readmission in the adult population. Given its poor prognosis, one could describe it as a "malignant condition". Acute decompensation is intrinsically related to increased right heart tele-diastolic pressures and often related to congestive symptoms. In-hospital strategies to adequately compensate and timely discharge patients are limited. Conversely, the fragile early postdischarge phase is a vulnerable period when one could potentially intervene cost-effectively to improve survival and to reduce morbidity. Promising transitional hospital-to-home programs may have a broader role in the near future, namely for selected higher risk patients. However, identifying patients at risk for hospital readmission has been challenging. Novel approaches, such as ferric carboxymaltose and valsartan/sacubitril, and reemerging drugs, particularly digoxin, may reduce hospitalizations. Despite this, optimizing the use of "older" therapies is still warranted. Right heart pressures monitoring may provide novel insights into promptly outpatient management. Unfortunately, randomized trials in the specific ADHF population are scarce. A novel paradigmatic approach is needed in order to suitably improve the currently poor prognosis of ADHF. Both improving survival and reducing hospitalizations are, therefore, primordial therapy goals. Lastly, no single drug has consistently proved to improve survival in HF with preserved ejection fraction (HFpEF); yet, some approaches may efficiently reduce hospitalizations. Awareness on HFpEF management beyond the failing heart is imperative.

Treatment of Heart Failure With Reduced Ejection Fraction-Recent Developments.

Heart failure with reduced ejection fraction (HFrEF) represents at least half of the cases of heart failure, which is a syndrome defined as the inability of the heart to supply the body's tissues with an adequate amount of blood under conditions of normal cardiac filling pressure. HFrEF is responsible for high costs and rates of mortality, morbidity, and hospital admissions, mainly in developed countries. Thus, the need for better diagnostic methods and therapeutic approaches and consequently better outcomes is clear. In this article, we review the principal aspects of pathophysiology and diagnosis of HFrEF, with focus on emerging biomarkers and on recent echocardiographic methods for the assessment of left ventricular function. Furthermore, we discuss several major developments in pharmacological and nonpharmacological treatment of HFrEF in the last years, including cardiac resynchronization therapy, implantable cardioverter defibrillators, and the recent and promising drug LCZ696, focusing on current indications, unanswered questions, and other relevant aspects.

Giant cell arteritis: a closer look at its ophthalmological manifestations.

Giant cell arteritis with ocular involvement is an ocular emergency. Arteritic anterior ischaemic optic neuropathy (AAION) is the most common ophthalmological manifestation associated with this disease. Visual loss is usually permanent with rare cases showing visual recovery. Visual improvement, if it occurs, is generally limited, and the visual field defects are persistent and severe. The main goal of AAION treatment is the preservation of vision in the fellow eye. In patients with neurophthalmological manifestations, high-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter. We present a case of AAION and severe vision loss where significant visual recovery was seen after treatment.

Galectin-3, a prognostic marker--and a therapeutic target?

The natriuretic peptides BNP and NT-proBNP are currently the most commonly used biomarkers in heart failure, but they have limitations. There is thus a need to identify new biomarkers that may prove useful, alone or in combination, for screening, diagnosis and prognosis. Galectin-3 is a protein involved in a variety of cellular signaling pathways and is found in many tissues. Its expression is low in normal hearts but elevated in fibrotic hearts. Among other effects, it promotes fibroblast proliferation and collagen synthesis, contributing to the cardiac remodeling that is central to the development and progression of heart failure. Heart failure associated with elevated galectin-3 (>17.8 ng/ml) affects 30-50% of patients with chronic heart failure, and is a marker of worse prognosis, with higher rates of short-term rehospitalization and mortality. It is thought that galectin-3 inhibition, or even genetic disruption, may reverse or delay disease progression. Galectin-3 appears to have greater prognostic value than natriuretic peptides when assessed separately, however, when combined their prognostic value is even higher. Galectin-3, associated with BNP or NT-proBNP, may help improve the diagnosis and prognosis of heart failure.

[Bilateral facial palsy and acute myeloid leukemia: an unusual association]. / Paralisia facial bilateral e leucemia mielóide aguda: uma associação pouco comum.

Acute myeloid leukemia (AML) is a malignant disease of the hematopoietic tissue. The disease presentation may be related to the loss of bone marrow function or with general symptoms of neoplastic diseases. Extramedullary involvement is responsible for less frequent presentations that may hinder early diagnosis. Gingival enlargement is not uncommon in AML but cases of bilateral facial palsy are rare. In this article the authors present the case of a man of 70 who comes up with gingival hypertrophy that initially was not valued and that developed after three weeks, a bilateral facial palsy. The myelogram revealed an AML. With directed chemotherapy the patient reached complete remission but kept the symptoms of disease presentation.

[Pulmonary abcess, a revision]. / Os abcessos pulmonares em revisão.

Lung abscesses are cavitating lesions containing necrotic debris caused by microbial infection. Patients with chronic lung disease, bronchial obstruction secondary to cancer, a history of aspiration or risk of aspiration caused by alcoholism, altered mental status, structural or physiologic alterations of the pharynx and esophagus, neuromuscular disorders, anesthesia, are among others at higher risk of developing lung abcess. The main bacteriological characteristics, the diagnosis, therapy and prognosis are considered. The problem of antimicrobial resistance is also referred.