Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Brazilian Guideline on Menopausal Cardiovascular Health ­ 2024 / Guía Brasileña de Salud Cardiovascular en el Climaterio y la Menopausia ­ 2024 / Diretriz Brasileira sobre a Saúde Cardiovascular no Climatério e na Menopausa ­ 2024

Women, who represent approximately half of the global population according to estimates as of January 2024, may experience signs and symptoms of menopause for at least one-third of their lives, during which they have a higher risk of cardiovascular morbidity and mortality. The effects of menopausal hormone therapy (MHT) on the progression of atherosclerosis and cardiovascular disease (CVD) events vary depending on the age at which MHT is initiated and the time since menopause until its initiation. Beneficial effects on CVD outcomes and all-cause mortality have been observed when MHT was initiated before the age of 60 or within 10 years after menopause. The decision regarding the initiation, dose, regimen, and duration of MHT should be made individually after discussing the benefits and risks with each patient. For primary prevention of postmenopausal chronic conditions, the combined use of estrogen and progestogen is not recommended in asymptomatic women, nor is the use of estrogen alone in hysterectomized women. Hormone-dependent neoplasms contraindicate MHT. For the treatment of genitourinary syndrome of menopause, vaginal estrogen therapy may be used in patients with known cardiovascular risk factors or established CVD. For women with contraindications to MHT or who refuse it, non-hormonal therapies with proven efficacy (antidepressants, gabapentin, and fezolinetant) may improve vasomotor symptoms. Compounded hormonal implants, or "bioidentical" and "compounded" hormones, and "hormone modulation" are not recommended due to lack of scientific evidence of their effectiveness and safety.

Mujeres, que representan aproximadamente la mitad de la población mundial según estimaciones de enero de 2024, pueden experimentar signos y síntomas de la menopausia durante al menos un tercio de sus vidas, durante los cuales tienen un mayor riesgo de morbilidad y mortalidad cardiovascular. Los efectos de la terapia hormonal de la menopausia (THM) en la progresión de la aterosclerosis y los eventos de enfermedad cardiovascular (ECV) varían según la edad en que se inicia la THM y el tiempo transcurrido desde la menopausia hasta su inicio. Se han observado efectos beneficiosos en los resultados de ECV y la mortalidad por todas las causas cuando la THM se inició antes de los 60 años o dentro de los 10 años posteriores a la menopausia. La decisión sobre la iniciación, dosis, régimen y duración de la THM debe tomarse individualmente después de discutir los beneficios y riesgos con cada paciente. Para la prevención primaria de condiciones crónicas en la posmenopausia, no se recomienda el uso combinado de estrógeno y progestágeno en mujeres asintomáticas, ni el uso de estrógeno solo en mujeres histerectomizadas. Las neoplasias dependientes de hormonas contraindican la THM. Para el tratamiento del síndrome genitourinario de la menopausia, se puede usar terapia estrogénica vaginal en pacientes con factores de riesgo cardiovascular conocidos o ECV establecida. Para mujeres con contraindicaciones a la THM o que la rechazan, las terapias no hormonales con eficacia demostrada (antidepresivos, gabapentina y fezolinetant) pueden mejorar los síntomas vasomotores. Los implantes hormonales compuestos, o hormonas "bioidénticas" y "compuestas", y la "modulación hormonal" no se recomiendan debido a la falta de evidencia científica sobre su efectividad y seguridad.

As mulheres, que representam cerca de metade da população mundial segundo estimativas de janeiro de 2024, podem sofrer com sinais e sintomas da menopausa durante pelo menos um terço de suas vidas, quando apresentam maiores risco e morbimortalidade cardiovasculares. Os efeitos da terapia hormonal da menopausa (THM) na progressão de eventos de aterosclerose e doença cardiovascular (DCV) variam de acordo com a idade em que a THM é iniciada e o tempo desde a menopausa até esse início. Efeitos benéficos nos resultados de DCV e na mortalidade por todas as causas ocorreram quando a THM foi iniciada antes dos 60 anos de idade ou nos 10 anos que se seguiram à menopausa. A decisão sobre o início, a dose, o regime e a duração da THM deve ser tomada individualmente após discussão sobre benefícios e riscos com cada paciente. Para a prevenção primária de condições crônicas na pós-menopausa, não se recomendam o uso combinado de estrogênio e progestagênio em mulheres assintomáticas nem o uso de estrogênio sozinho em mulheres histerectomizadas. Neoplasias hormônio-dependentes contraindicam a THM. Para tratamento da síndrome geniturinária da menopausa, pode-se utilizar terapia estrogênica por via vaginal em pacientes com fatores de risco cardiovascular conhecidos ou DCV estabelecida. Para mulheres com contraindicação à THM ou que a recusam, terapias não hormonais com eficácia comprovada (antidepressivos, gabapentina e fezolinetante) podem melhorar os sintomas vasomotores. Os implantes hormonais manipulados, ou hormônios "bioidênticos" "manipulados", e a 'modulação hormonal' não são recomendados pela falta de evidência científica de sua eficácia e segurança.

How diverse are the mountain karst forests of Mexico?

Tropical forests on karstic relief (tropical karst forest) are among the most species-rich biomes. These forests play pivotal roles as global climate regulators and for human wellbeing. Their long-term conservation could be central to global climate mitigation and biodiversity conservation. In Mexico, karst landscapes occupy 20% of the total land surface and are distributed mainly in the southeast of the country, along the eastern slope, and in the Yucatan Peninsula. Within each of these areas, the following types of karst occur: coastal karst, plain karst, hill karst, and mountain karst (low, medium, high). Mountain karst cover 2.07% of Mexico's land surface and are covered by tropical rainforests, montane cloud forests, and tropical deciduous forests. These are probably one of the most diverse biomes in Mexico. However, the mountain karst forests of Mexico have received little attention, and very little is known about their diversity. Here, we evaluated the vascular plant species richness within the mountain karst forests of Mexico. We assembled the first, largest, and most comprehensive datasets of Mexican mountain karst forest species, from different public databases (CONABIO, GBIF, IBdata-UNAM), which included a critical review of all data. We compiled a list of the families, genera, and species present within the mountain karst forests of Mexico. Taxa that best characterize these forests were identified based on their spatial correlation with this biome. We explored biodiversity patterns, identifying areas with the highest species richness, endemism centers, and areas of relatively low sampling intensity. We found that within the mountain karst forests of Mexico there are representatives of 11,771 vascular plant species (253 families and 2,254 genera), ca. 50% of the Mexican flora. We identified 372 species endemic to these forests. According to preliminary IUCN red list criteria, 2,477 species are under some category of conservation risk, of which 456 (3.8%) are endangered. Most of the Mexican mountain karst forests have been extensively explored and six allopatric, species-rich areas were identified. Compared to other regions in the world, the mountain karst forests of Mexico are one of the most diverse biomes. They contain more species than some entire montane systems in Mexico such as Sierra Madre Oriental, and Sierra Madre del Sur. Also, the mountain karst forests of Mexico are most diverse than similar forests of South America and Asia, even if considering the effect of different sampling areas. The fact that mountain karst forests are embedded in areas of high biotic diversity, probably contributes to their great floristic diversity. Thus, the mountain karst forests of Mexico are an important source of diversity and shelters a large percentage of the Mexican flora.

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA).

Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-ß-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation: The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics. Funding: The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).

May Measurement Month 2017-19: an analysis of blood pressure screening results from Paraguay.

The aim of this study was to highlight the importance of measuring blood pressure (BP) and to identify and reduce the BPs of those people who require intervention to lower their BP according to current guidelines. A total of 7782 individuals aged ≥18 years were recruited during the 3 years of the May Measurement Month (MMM) campaign (2017: 1196, 2018: 2285, 2019: 4301). Recruitment was through opportunistic sampling at a variety of screening sites distributed throughout the country. Each participant underwent a pre-specified questionnaire with questions on risk factors concluding with three BP measurements at 1 min intervals and measurement of weight and height. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg or those receiving antihypertensive therapy. Of all 7782 participants, 3323 had hypertension (42.7%) of whom 61.8% were aware and 50.4% were not receiving antihypertensive medication. Of those treated (49.6%), 43.8% had controlled BP (<140/90 mmHg). Among all hypertensive patients (with and without medication), 21.7% had controlled BP. In relation to previous surveys carried out in the country, awareness of hypertension increased two-fold, with no change in the proportion of hypertensive patients on treatment and the proportion of hypertensive patients with controlled BP which remained low.

In Vitro and In Vivo Characterization of a Broadly Neutralizing Anti-SARS-CoV-2 Antibody Isolated from a Semi-Immune Phage Display Library.

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 have shown reduced efficacy or have failed to neutralize the variants of concern (VOCs), particularly B.1.1.529 (Omicron). Previously, we reported the discovery and characterization of antibodies with high affinity for SARS-CoV-2 RBD Wuhan (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron) strains. One of the antibodies, called IgG-A7, also blocked the interaction of human angiotensin-converting enzyme 2 (hACE2) with the RBDs of the three strains, suggesting it may be a broadly SARS-CoV-2 neutralizing antibody. Herein, we show that IgG-A7 efficiently neutralizes all the three SARS-CoV-2 strains in plaque reduction neutralization tests (PRNTs). In addition, we demonstrate that IgG-A7 fully protects K18-hACE2 transgenic mice infected with SARS-CoV-2 WT. Taken together, our findings indicate that IgG-A7 could be a suitable candidate for development of antibody-based drugs to treat and/or prevent SARS-CoV-2 VOCs infection.

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Anti-SARS-CoV-2 Omicron Antibodies Isolated from a SARS-CoV-2 Delta Semi-Immune Phage Display Library.

This report describes the discovery and characterization of antibodies with potential broad SARS-CoV-2 neutralization profiles. The antibodies were obtained from a phage display library built with the VH repertoire of a convalescent COVID-19 patient who was infected with SARS-CoV-2 B.1.617.2 (Delta). The patient received a single dose of Ad5-nCoV vaccine (Convidecia™, CanSino Biologics Inc.) one month before developing COVID-19 symptoms. Four synthetic VL libraries were used as counterparts of the immune VH repertoire. After three rounds of panning with SARS-CoV-2 receptor-binding domain wildtype (RBD-WT) 34 unique scFvs, were identified, with 27 cross-reactive for the RBD-WT and RBD Delta (RBD-DT), and seven specifics for the RBD-WT. The cross-reactive scFvs were more diverse than the RBD-WT specific ones, being encoded by several IGHV genes from the IGHV1 and IGHV3 families combined with short HCDR3s. Six cross-reactive scFvs and one RBD-WT specific scFv were converted to human IgG1 (hIgG1). Out of the seven antibodies, six blocked the RBD-WT binding to angiotensin converting enzyme 2 (ACE2), suggesting these antibodies may neutralize the SARS-CoV-2 infection. Importantly, one of the antibodies also recognized the RBD from the B.1.1.529 (Omicron) isolate, implying that the VH repertoire of the convalescent patient would protect against SARS-CoV-2 Wildtype, Delta, and Omicron. From a practical viewpoint, the triple cross-reactive antibody provides the substrate for developing therapeutic antibodies with a broad SARS-CoV-2 neutralization profile.

Examining the immune signatures of SARS-CoV-2 infection in pregnancy and the impact on neurodevelopment: Protocol of the SIGNATURE longitudinal study.

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Asociación de la dilatación auricular izquierda con los trastornos del sistema de conducción en pacientes con hipertensión arterial sistémica / Association of left atrial dilatation with conduction system disorders in patients with systemic arterial hypertension

La dilatación de la aurícula izquierda (AI) se considera un predictor ecocardiográfico para la remodelación auricular y la fibrilación auricular. Por ende, hemos investigado la correlación existente entre la dilatación de la AI con las arritmias cardíacas y los trastornos del sistema de conducción en pacientes con hipertensión arterial (HTA). En este estudio observacional y prospectivo hemos investigado las variaciones electrocardiográficas, mediciones ecocardiográficas y Holter ECG de 24 hs en pacientes hipertensos y no hipertensos ambulatoria y hospitalizados que acuden a un hospital terciario entre marzo a septiembre del 2018. Se estudiaron 104 pacientes, 65 hipertensos conocidos y 39 no hipertensos como grupo control. El diámetro promedio de la AI fue significativamente mayor (p=0,03) en pacientes hipertensos que los no hipertensos (37±8 mm vs. 34±5 mm). Se encontró una asociación significativa entre hipertensión y la aurícula izquierda dilatada (>40 mm) (p= 0,026 OR: 3,25 IC95%: 1,01-11,02). La dilatación de la AI tuvo una especificidad de 73% y un valor predictivo negativo de 98% relacionado con la presencia de trastornos del sistema de conducción y arritmias cardiacas en pacientes con HTA. Se encontró asociación entre la hipertensión arterial y la dilatación de la aurícula izquierda. La dilatación de la aurícula izquierda tiene una elevada especificidad y un alto valor predictivo negativo en la detección de la presencia de prolongación del intervalo QT, ensanchamiento del complejo QRS, dispersión de la onda P, y trastornos del sistema de conducción y arritmias cardiacas en pacientes con hipertensión arterial(AU)

Dilation of the left atrium (LA) is considered an echocardiographic predictor for atrial remodeling and atrial fibrillation. Therefore, we have investigated the correlation between dilatation of the LA with cardiac arrhythmias and conduction system disorders in patients with systemic arterial hypertension. In this observational and prospective study we have investigated electrocardiographic variations, echocardiographic measurements and Holter ECG of 24 hours in hypertensive patients who attend a tertiary hospital from March 2018 to September 2018 as outpatients and inpatients. One hundred four patients were studied, 65 known to be hypertensive and 39 non-hypertensive subjects as control group. The diameter of the LA ​​had a mean value of 37±8 in hypertensive patients, while in non-hypertensive patients was 34±5 ​​(p = 0.03). A significant association was found between hypertension and increased diameter of the LA (p = 0.04 OR: 2.6 CI 0.88-7.7). Dilatation of the LA had a specificity of 73% and a negative predictive value of 98% related to the presence of conduction system disorders and cardiac arrhythmias in patients with hypertension. A significant relationship between arterial hypertension and dilatation of the left atrium was observed. The dilatation of the left atrium has a high specificity and a high negative predictive value in the detection of the presence of prolongation of the QT interval, widening of the QRS complex, dispersion of the P wave, and disorders of the conduction system and cardiac arrhythmias in patients with hypertension(AU)

Correlación entre la dispersión de la onda P con las arritmias cardíacas y los trastornos del sistema de conducción en pacientes con hipertensión arterial del Hospital de Clínicas, Asunción-Paraguay / Correlation among P wave dispersion and cardiac arrhythmias and alterations of the conduction system in patients with arterial hypertension from the Hospital de Clinicas, Asunción, Paraguay

RESUMEN Introducción: La hipertensión arterial puede producir cambios auriculares que generan arritmias auriculares. La dispersión de la onda P (PWD) se considera un marcador electrocardiográfico no invasivo para la remodelación auricular y un predictor para el desarrollo de fibrilación auricular. Nuestro objetico es estudiar la correlación entre la dispersión de la onda P con las arritmias cardíacas y los trastornos del sistema de conducción en pacientes con hipertensión arterial (HTA). Metodología: Estudio observacional y prospectivo en el que estudiamos las variaciones electrocardiográficas, mediciones ecocardiográficas y Holter ECG de 24 hs en pacientes hipertensos que acuden a un hospital terciario desde marzo del 2018 a septiembre del 2018 en forma ambulatoria y a internados. Resultados: Se estudiaron 104 pacientes, 65 hipertensos conocidos y 39 no hipertensos como grupo control. El valor promedio de la dispersión de la onda P en hipertensos fue de 37±8 ms, y en el grupo control fue de 27±13 ms, P <0,001. Además se encontró una diferencia significativa entre estos dos grupos en la duración máxima de la onda P (p<0,05), y el diámetro de la aurícula izquierda (p<0,05). La PWD posee una especificidad de 72% y un valor predictivo negativo de 78% relacionado con la presencia de trastornos del sistema de conducción y arritmias cardiacas en pacientes con HTA. Además, la PWD posee una especificidad de 73% y un valor predictivo negativo de 83% relacionado con la presencia de ensanchamiento del complejo QRS. Conclusiones: Existe una mayor alteración significativa en la dispersión de la Onda P, la Onda P máxima, y la dilatación de la aurícula izquierda en HTA. También se observó una correlación significativa entre la dispersión de la onda P y el riesgo de desarrollar arritmias auriculares. La dispersión de la onda P tiene una elevada especificidad y un alto valor predictivo negativo en la detección de la presencia de prolongación del intervalo QT, ensanchamiento del complejo QRS, dilatación de la aurícula izquierda y trastornos del sistema de conducción y arritmias cardiacas en pacientes con hipertensión arterial. Palabras clave: Dispersión de la Onda P; Hipertensión arterial; Arritmias cardiacas.

Introduction:High blood pressure can produce atrial changes that generate atrial arrhythmias. P wave dispersion (PWD) is considered a noninvasive electrocardiographic marker for atrial remodeling and a predictor for the development of atrial fibrillation. Our objective is to study the correlation between the dispersion of the P wave with cardiac arrhythmias and conduction system disorders in patients with arterial hypertension (AHT). Methodology:Observational and prospective study in which we studied the electrocardiographic variations, echocardiographic measurements and Holter ECG of 24 hours in hypertensive patients who attend a tertiary hospital from March 2018 to September 2018 on an outpatient basis. Results:104 patients were studied, 65 known hypertensive patients and, 39 non-hypertensive as control group. The average value of the P wave dispersion in hypertensive patients was 37±8 ms, and in the control group it was 27±13 ms, P <0.001. In addition, a significant difference between these two groups was found in the maximum duration of the P wave (p <0.05), and the diameter of the left atrium (p <0.05). The PWD has a specificity of 72% and a negative predictive value of 78% related to the presence of disorders of the conduction system and cardiac arrhythmias in patients with hypertension. In addition, the PWD has a specificity of 73% and a negative predictive value of 83% related to the presence of the widening of the QRS complex. Conclusion:There is a greater significant alteration in the P Wave dispersion, the maximum P Wave, and the dilatation of the left atrium in AHT. A significant correlation was also observed between the dispersion of the P wave and the risk of developing atrial arrhythmias. The P wave dispersion has a high specificity and a high negative predictive value in the detection of the presence of QT interval prolongation, widening of the QRS complex, dilatation of the left atrium and disorders of the conduction system and cardiac arrhythmias in patients with arterial hypertension. Key words: P wave dispersion Arterial Hypertensión Cardiac arrhythmias

Asociación de la dilatación auricular izquierda con alteraciones hemodinámicas del ventrículo izquierdo en pacientes con Hipertensión Arterial del Hospital de Clínicas. Asunción, Paraguay / Association of left atrial dilatation with hemodynamic alterations of the left ventricle in patients with arterial hypertension of the Hospital de Clinicas. Asuncion, Paraguay

Introducción: La dilatación de la aurícula izquierda (AI) se considera un marcador ecocardiográfico para la remodelación auricular y la fibrilación auricular. Por ende, hemos investigado la correlación entre la dilatación de la AI con las alteraciones hemodinámicas del ventrículo izquierdo en pacientes con hipertensión arterial. Objetivo: Determinar la relación existente entre la hipertensión arterial y la dilatación auricular izquierda. Así mismo determinar las características epidemiológicas de la población en estudio y las diferencias ecocardiográficas entre pacientes hipertensos y pacientes sin HTA. Metodología: En este estudio observacional y prospectivo hemos investigado las variaciones electrocardiográficas, mediciones ecocardiográficas y Holter ECG de 24 hs en pacientes hipertensos que acuden a un hospital terciario desde marzo a septiembre del 2018 en forma ambulatoria y a internados en el Hospital de Clínicas. Resultados: Se estudiaron 104 pacientes, 65 hipertensos conocidos y 39 no hipertensos como grupo control. El diámetro de la AI tuvo una media de 37±8 en pacientes hipertensos, mientras que en pacientes no hipertensos la media fue de 34±5 (p=0,03). Se encontró una asociación significativa entre hipertensión y aumento del diámetro de la AI (p=0,04 OR: 2,6 IC 0,88­7,7). En los pacientes hipertensos se observó una asociación significativa entre la aurícula izquierda dilatada y la fracción de eyección disminuida (p= 0,01 OR: 4,66 IC: 1,28­16,98). Además, una asociación significativa entre la AI dilatada y el diámetro diastólico aumentado del ventrículo izquierdo (VI) (p= 0,0004 OR: 8,75 IC 2,18­35,01). Se observó una asociación significativa entre la presencia de una AI dilatada y el diámetro sistólico del VI aumentado en hipertensos (p= 0,006 OR: 5,74 IC 1,5­21,91). Conclusiones: Hubo una relación significativa entre la hipertensión arterial y la dilatación de la aurícula izquierda. Los pacientes hipertensos con una dilatación de la AI tuvieron un aumento significativo de los diámetros sistólicos y diastólicos del ventrículo izquierdo, así como una disminución significativa de la funcionalidad sistólica del ventrículo izquierdo. Por ende, los pacientes hipertensos que tienen una dilatación de la aurícula izquierda presentaron además alteraciones hemodinámicas asociadas del ventrículo izquierdo. Palabras clave: Dilatación de la aurícula izquierda; Hipertensión arterial; Fracción de eyección del VI. Diámetro sistólico y diastólico del VI.

Introduction: Dilation of the left atrium (LA) is considered an echocardiographic marker for atrial remodeling and atrial fibrillation. Therefore, we have investigated the correlation between dilatation of the IA with hemodynamic alterations of the left ventricle in patients with arterial hypertension. Objetive: Determine the relationship between arterial hypertension and left atrial dilatation. The same epidemiological characteristics of the study population and the echocardiographic differences between hypertensive patients and patients without HTN. Methodology: In this observational and prospective study we have investigated electrocardiographic variations, echocardiographic measurements and Holter ECG of 24 hours in hypertensive patients who attend a tertiary hospital from March 2018 to September 2018 as outpatients and inpatients. Results: 104 patients were studied, 65 known hypertensive patients and, 39 non-hypertensive as control group. The diameter of the AI had a mean of 37 ± 8 in hypertensive patients, while in non-hypertensive patients the mean was 34 ± 5 (p = 0.03). A significant association was found between hypertension and increased diameter of the LA (p = 0.04 OR: 2.6 CI 0.88-7.7). In hypertensive patients, a significant association was observed between the dilated left atrium and the decreased ejection fraction (p = 0.01 OR: 4.66 CI: 1.28- 16.98). In addition, a significant association between dilated LA and the increased diastolic diameter of the LV (p = 0.0004 OR: 8.75 IC 2.18-35.01). A significant association was observed between the presence of dilated IA and the left ventricular systolic diameter increased in hypertensive patients (p = 0.006 OR: 5.74 CI 1.5-21.91). Conclusion: There was a significant relationship between arterial hypertension and dilatation of the left atrium. Hypertensive patients with dilatation of the IA had a significant increase in systolic and diastolic diameters of the left ventricle, as well as a significant decrease in systolic functionality of the left ventricle. Therefore, hypertensive patients who have dilation of the left atrium also had associated hemodynamic alterations of the left ventricle. Key words: Dilation of the left atrium; Arterial hypertension; LV ejection fraction. Systolic and diastolicdiameter of the LV.

Niveles sanguíneos de digoxina en pacientes con fibrilación auricular y su relación con alteraciones de la repolarización y arritmias ventriculares. Hospital de Clínicas. FCM-UNA, Paraguay / Plasma levels of digoxin in patients with atrial fibrillation and its relation to alterations of repolarization and ventricular arrhythmias. Hospital de Clínicas, FCM-UNA, Paraguay

Introducción: La fibrilación auricular es la arritmia sostenida más común en el campo de la medicina interna, con prevalencia de 1% y riesgo de vida 25% aproximadamente, después de los 40 años. Estudios previos para examinar la seguridad de la digoxina en pacientes con fibrilación auricular, presentan como limitación, la falta de determinaciones de la concentración sérica de este fármaco, necesarias para definir una posible relación entre dosis y respuesta. Metodología: Estudio prospectivo, descriptivo, de corte transversal con componente analítico,se analizó el valor de la digoxina en sangre, los tipos de arritmias cardiacas concomitantes con la fibrilación auricular, factores de riesgo, dosis diaria de digoxina recibida, en pacientesambulatorios de la División de Medicina Cardiovascular-Hospital de Clínicas, de julio a octubre de 2018. Resultados: De 48 pacientes, 5 (10%) tenían una digoxinemia mayor a 1,2ng/ml, y 43 (90%) pacientes tenían una digoxinemia menor a 1,2ng/ml.Del total de pacientes, 18 (38%) pacientes recibían una dosis diaria de 0,25 mg y 30 (62%) pacientes una dosis diaria menor a 0,25 mg.El trastorno del sistema de conducción más frecuente encontrado fue la alteración de la repolarización (20%), la presencia de ondas Q (9%), las alteraciones de la repolarización con extrasístoles ventriculares y la presencia de ondas T negativas (7%), la presencia de bloqueo completo de rama derecha y hemibloqueo anterior izquierdo (5%).Se encontró una asociación significativa entre la dosis de digoxina y la digoxinemia en rango normal (p=0,03); también se halló una asociación significativa entre la digoxinemia alta y alteraciones de la repolarización(p=0,0005). Se halló asociación entre la digoxinemia alta y la presencia de aurícula izquierda dilatada (p=0,001 OR: 0,8 IC 0,6 - 1,03). Conclusión: La mayoría de los pacientes presentaron digoxinemia en rango de seguridad es decir menor a 1,2 ng. La mayoría de los pacientes recibían una dosis menor a 0,25 mg. Existe asociación significativa entre la dosis de digoxina y la digoxinemia sérica. También encontramos asociación significativa entre la digoxinemia alta y las alteraciones de la repolarización y la presencia de aurícula izquierda dilatada. Palabras clave: Fibrilación auricular; Arritmias ventriculares; Dilatación auricular izquierda

Introduction: Atrial fibrillation is the most common sustained arrhythmia in the field of internal medicine, with prevalence of 1% and risk of life 25% approximately, after 40 years. Previous studies to examine the safety of digoxin in patients with atrial fibrillation have as limitation, the lack of determinations of the serum concentration of this drug, necessary to define a possible relationship between dose and response. Methodology: Prospective, descriptive, cross-sectional study with analytical component, the value of digoxin in blood was analyzed the types of cardiac arrhythmias concomitant with atrial fibrillation, risk factors, daily dose of digoxin received, in ambulatory patients from the Division of Cardiovascular Medicine-Hospital de Clínicas, from July to October 2018. Results: Of 48 patients, 5 (10%) had a digoxinemia greater than 1.2 ng / ml, and 43 (90%) patients had digoxinemia less than 1.2 ng / ml. Of the total patients, 18 (38%) patients received a daily dose of 0.25 mg and 30 (62%) patients a daily dose of less than 0.25 mg. The most frequent conduction system disorder found was the alteration of repolarization (20%), the presence of Q waves (9%), the alterations of repolarization with ventricular premature beats and the presence of negative T waves (7%), the presence of complete blockage of the right bundle branch and left anterior hemiblock (5%). A significant association was found between the dose of digoxin and digoxinaemia in the normal range (p = 0.03); A significant association was also found between high digoxinemia and alterations in repolarization (p = 0.0005). An association was found between high digoxinemia and the presence of a dilated left atrium (p = 0.001 OR: 0.8 CI 0.6 - 1.03). Conclusion: The majority of patients presented digoxinemia in a safety range, that is, less than 1.2 ng. The majority of patients received a dose of less than 0.25 mg. There is a significant association between digoxin dose and serum digoxinemia. We also found a significant association between high digoxinemia and alterations in repolarization and the presence of a dilated left atrium. Keywords: Atrial fibrillation; Ventricular arrhythmias; Left atrial dilatation.

Similar recovery of liver function after response to all-oral HCV therapy in patients with cirrhosis with and without HIV coinfection.

Among patients with cirrhosis, recovery of liver function after SVR to all-oral direct-acting antivirals (DAA) in HIV/HCV coinfection could be different to that in HCV monoinfection. Because of this, we compared the changes in several markers of liver function between HCV-monoinfected and HIV/HCV-coinfected patients with cirrhosis who achieved SVR12 to DAA combinations. In this retrospective cohort study, cirrhotics included in the HEPAVIR-DAA and GEHEP-MONO cohorts were selected if they had SVR12 to all-oral DAAs. Patients treated with atazanavir were excluded. Liver function improvement was defined as Child-Pugh-Turcotte (CPT) decrease ≥1 and/or MELD decrease ≥2 between baseline and SVR12. Liver function worsening was defined as a CPT increase ≥1 and/or MELD increase ≥2 and/or decompensations between baseline and SVR12. We included 490 patients, 270 (55%) of them with HIV coinfection. Liver function improved in 50 (56%) HCV-infected individuals and in 82 (57%) HIV/HCV-coinfected patients (P = 0.835). Liver function worsened in 33 (15%) HCV-monoinfected patients and in 33 (13%) HIV/HCV-coinfected patients (P = 0.370). Factors independently related with liver function improvement were male gender [adjusted OR (AOR) 2.1 (95% confidence interval, 95% CI: 1.03-4.2), P = 0.040], bilirubin < 1.2 mg/dL (AOR 1.8 [95% CI: 1.004-3.3], P = 0.49), and INR < 1.3 (AOR 2.4 [95% CI: 1.2-5.0], P = 0.019) at baseline. After multivariate analysis, albumin < 3.5 g/dL was associated with liver function worsening (AOR 6.1 [95% CI: 3-12.5], P < 0.001). Liver function worsening and improvement rates after responding to DAA are similar among HCV-monoinfected and HIV/HCV-coinfected cirrhotics. Gender, INR, bilirubin, and albumin levels were associated with liver function changes after response to DAAs.

Factores de riesgo y cardiopatías prevalentes en mujeres internadas en la división de medicina cardiovascular del hospital de clínicas / Risk factors and prevalent cardiopathies in hospitalized women in the cardiovascular medicine division of the clinical hospital

La representación de las mujeres ha sido marginal en la mayoría de los ensayos clínicos o registros dedicados a las enfermedades cardiovasculares (ECV). Por eso, recientemente, se ha adoptado una política de estimular la inclusión de mujeres en los ensayos clínicos. En este estudio descriptivo retrospectivo y de corte transversal, nos hemos propuesto determinar la forma de presentación de las cardiopatías, describir los factores de riesgo cardiovasculares presentes en estas pacientes, determinar el número de mujeres que presentaron cardiopatía isquémica, y establecer el tratamiento recibido por las mujeres que presentaron cardiopatía isquémica en mujeres internadas en la División de Medicina Cardiovascular del Hospital de Clínicas. El estudio incluyó un total de 250 pacientes, de los cuales 187 (75%) correspondían al sexo masculino y 63 (25%) al sexo femenino. Las edades de las mujeres se encontraban entre 25 y 94 años (60±7,3 años). Las mujeres estudiadas presentaron: insuficiencia cardiaca 26 (41%), síndromes coronarios agudos 20 (32%), valvulopatías 8 (13%), bloqueo AV completo 7 (11%) y otros 2 (3%). De las mujeres con síndrome coronario agudo, 3 pacientes tuvieron enfermedad de 3 vasos, 1 sola tuvo coronarias normales, y 8 (40%) tenían lesiones de la arteria descendente anterior. Los factores de riesgo más frecuentes fueron el sedentarismo en la totalidad de las mujeres, la hipertensión arterial en 55 (87%), dislipidemias en 39 (62%), obesidad en 34 (54%), diabetes mellitus tipo 2 en 12 (19%) y tabaquismo en 12 pacientes (19%). La magnitud del riesgo cardiovascular de la mujer depende no solamente de la alteración de un parámetro sino también de la presencia de otros factores de riesgo, razón por la cual se requiere de un manejo multifactorial integral dentro del concepto de riesgo cardiovascular global en la mujer.

Most of the clinical trials on cardiovascular diseases had scant women representation inthe population studied. Hence, there has been a movement to stimulate the inclusion ofmore women in the clinical studies. In this present descriptive retrospective cross-sectionalstudy we aimed to determine the form of presentation of cardiopathies, to describe thecardiovascular risk factors, to determine the incidence of ischemic cardiopathy and the treatment received in hospitalized women in the Division of Cardiovascular Medicine of theClinical Hospital. The study included 250 patients with 187 male patients (75%) and 63(25%) female patients. The age of the women was between 25 and 94 years old, with anaverage of 60±7,3 years. The women had heart failure 26 (41%), acute coronary syndrome20 (32%), valvulopathy 8 (13%), and complete AV block 7 (11%). Out of the women withacute coronary syndrome, 3 patients had three vessel disease, only 1 had normal coronaryarteries, and 8 patients had stenosis of the anterior descendent coronary artery. All womenhad sedentary lifestyle as cardiovascular risk factor, 55 (87%) arterial hypertension, 39(62%) dyslipidemia, 34 (54%) obesity, 12 (19%) type II diabetes mellitus, and 12 (19%)smoking. The magnitude of the cardiovascular risk factors in women depends not only onthe alteration of one parameter but also on the presence of other risk factors. Therefore, anadequate integral multifactorial management in the global concept of cardiovascular riskfactor in women is required.