Mortality risk score for patients with Chagas cardiomyopathy and pacemaker.

BACKGROUND: Prognosis of Chronic Chagasic Cardiomyopathy (CCC) patients depends on functional and clinical factors. Bradyarrhythmia requiring pacemaker is a common complication. Prognosis of these patients is poorly studied, and mortality risk factors are unknown. We aimed to identify predictors of death and to define a risk score for mortality in a large cohort of CCC patients with pacemaker. METHODS: It was an observational, unicentric and prospective study. The endpoint was all-cause mortality. Cox regression was used to identify predictors of death and to define a risk score. Bootstrapping method was used to internal score validation. RESULTS: We included 555 patients and after a mean follow-up of 3.7±1.5 years, 100 (18%) deaths occurred. Predictors of death were: right ventricular dysfunction (HR [hazard ratio] 2.24; 95%CI 1.41-3.53; P = 0.001); heart failure class III or IV (HR 2.16; 95% confidence interval [95%CI] 1.16-4.00; P = 0.014); renal disease (HR 2.14; 95%CI 1.24-3.68; P = 0.006); left ventricular end-systolic diameter > 44mm (HR 1.97; 95%CI 1.26-3.05; P = 0.003); atrial fibrillation (HR 1.94; 95%CI 1.25-2.99; P = 0.003) and cardiomegaly on X-ray (HR 1.87; 95%CI 1.10-3.17; P = 0.020). The score identified patients with: low (0-20 points), intermediate (21-30 points) and high risk (>31points). The optimism-corrected C-statistic of the predictive model was 0.751 (95% CI 0.696-0.806). Internal validation with bootstrapping revealed a calibration slope of 0.946 (95% CI 0.920-0.961), reflecting a small degree of over-optimism and C-statistic of 0.746 (95% CI 0.692-0.785). CONCLUSIONS: This study identified predictors of mortality in CCC patients with pacemaker defining a simple, validated and specific risk score.

The Six Pillars of Lifestyle Medicine in Managing Noncommunicable Diseases - The Gaps in Current Guidelines. / Os Seis Pilares da Medicina do Estilo de Vida no Manejo de Doenças Não Transmissíveis ­ As Lacunas nas Diretrizes Atuais.

BACKGROUND: Noncommunicable diseases (NCDs), also known as chronic diseases that are long-lasting, are considered the major cause of death and disability worldwide, and the six pillars of lifestyle medicine (nutrition, exercise, toxic control, stress management, restorative sleep, and social connection) play an important role in a holistic management of their prevention and treatment. In addition, medical guidelines are the most accepted documents with recommendations to manage NCDs. OBJECTIVE: The present study aims to analyze the lack of lifestyle pillars concerning the major Brazilian medical guidelines for NCDs and identify evidence in the literature that could justify their inclusion in the documents. METHOD: Brazilian guidelines were selected according to the most relevant causes of death in Brazil, given by the Mortality Information System, published by the Brazilian Ministry of Health in 2019. Journals were screened in the PUBMED library according to the disease and non-mentioned pillars of lifestyle. RESULTS: Relevant causes of deaths in Brazil are acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic obstructive pulmonary diseases (COPD). Six guidelines related to these NCDs were identified, and all address aspects of lifestyle, but only one, regarding cardiovascular prevention, highlights all six pillars. Despite this, a literature search involving over 50 articles showed that there is evidence that all the pillars can help control each of these NCDs. CONCLUSION: Rarely are the six pillars of lifestyle contemplated in Brazilian guidelines for AMI, DM, and COPD. The literature review identified evidence of all lifestyle pillars to offer a holistic approach for the management and prevention of NCDs.

FUNDAMENTO: As doenças crônicas não transmissíveis (DCNT), também conhecidas como doenças crônicas de longa duração, são consideradas a principal causa de morte e incapacidade em todo o mundo, e os seis pilares da medicina do estilo de vida (nutrição, exercício, controle de tóxicos, manejo do estresse, saúde do sono e conexão social) desempenham um papel importante na gestão holística da sua prevenção e tratamento. Além disso, as diretrizes médicas são os documentos mais aceitos com recomendações para o manejo das DCNT. OBJETIVO: O presente estudo tem como objetivo analisar a ausência de pilares de estilo de vida nas principais diretrizes médicas brasileiras sobre as DCNT e identificar evidências na literatura que possam justificar sua inclusão nos documentos. MÉTODO: As diretrizes brasileiras foram selecionadas de acordo com as causas de morte mais relevantes no Brasil, informadas pelo Sistema de Informações sobre Mortalidade publicado pelo Ministério da Saúde em 2019. Os periódicos foram selecionados na biblioteca PUBMED de acordo com a doença e os pilares do estilo de vida não mencionados. RESULTADOS: Causas relevantes de mortes no Brasil são o infarto agudo do miocárdio (IAM), o diabetes mellitus (DM) e as doenças pulmonares obstrutivas crônicas (DPOC). Foram identificadas seis diretrizes relacionadas a essas DCNT e todas abordam aspectos do estilo de vida, mas apenas uma, referente à prevenção cardiovascular, destaca todos os seis pilares. Apesar disso, uma pesquisa bibliográfica envolvendo mais de 50 artigos mostrou que há evidências de que todos os pilares podem ajudar no controle de cada uma dessas DCNT. CONCLUSÃO: Raramente os seis pilares do estilo de vida são contemplados nas diretrizes brasileiras para IAM, DM e DPOC. A revisão da literatura identificou evidências de todos os pilares do estilo de vida para oferecer uma abordagem holística para a gestão e prevenção das DCNT.

Os Seis Pilares da Medicina do Estilo de Vida no Manejo de Doenças Não Transmissíveis - As Lacunas nas Diretrizes Atuais / The Six Pillars of Lifestyle Medicine in Managing Noncommunicable Diseases - The Gaps in Current Guidelines

Resumo Fundamento: As doenças crônicas não transmissíveis (DCNT), também conhecidas como doenças crônicas de longa duração, são consideradas a principal causa de morte e incapacidade em todo o mundo, e os seis pilares da medicina do estilo de vida (nutrição, exercício, controle de tóxicos, manejo do estresse, saúde do sono e conexão social) desempenham um papel importante na gestão holística da sua prevenção e tratamento. Além disso, as diretrizes médicas são os documentos mais aceitos com recomendações para o manejo das DCNT. Objetivo: O presente estudo tem como objetivo analisar a ausência de pilares de estilo de vida nas principais diretrizes médicas brasileiras sobre as DCNT e identificar evidências na literatura que possam justificar sua inclusão nos documentos. Método: As diretrizes brasileiras foram selecionadas de acordo com as causas de morte mais relevantes no Brasil, informadas pelo Sistema de Informações sobre Mortalidade publicado pelo Ministério da Saúde em 2019. Os periódicos foram selecionados na biblioteca PUBMED de acordo com a doença e os pilares do estilo de vida não mencionados. Resultados: Causas relevantes de mortes no Brasil são o infarto agudo do miocárdio (IAM), o diabetes mellitus (DM) e as doenças pulmonares obstrutivas crônicas (DPOC). Foram identificadas seis diretrizes relacionadas a essas DCNT e todas abordam aspectos do estilo de vida, mas apenas uma, referente à prevenção cardiovascular, destaca todos os seis pilares. Apesar disso, uma pesquisa bibliográfica envolvendo mais de 50 artigos mostrou que há evidências de que todos os pilares podem ajudar no controle de cada uma dessas DCNT. Conclusão: Raramente os seis pilares do estilo de vida são contemplados nas diretrizes brasileiras para IAM, DM e DPOC. A revisão da literatura identificou evidências de todos os pilares do estilo de vida para oferecer uma abordagem holística para a gestão e prevenção das DCNT.

Abstract Background: Noncommunicable diseases (NCDs), also known as chronic diseases that are long-lasting, are considered the major cause of death and disability worldwide, and the six pillars of lifestyle medicine (nutrition, exercise, toxic control, stress management, restorative sleep, and social connection) play an important role in a holistic management of their prevention and treatment. In addition, medical guidelines are the most accepted documents with recommendations to manage NCDs. Objective: The present study aims to analyze the lack of lifestyle pillars concerning the major Brazilian medical guidelines for NCDs and identify evidence in the literature that could justify their inclusion in the documents. Method: Brazilian guidelines were selected according to the most relevant causes of death in Brazil, given by the Mortality Information System, published by the Brazilian Ministry of Health in 2019. Journals were screened in the PUBMED library according to the disease and non-mentioned pillars of lifestyle. Results: Relevant causes of deaths in Brazil are acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic obstructive pulmonary diseases (COPD). Six guidelines related to these NCDs were identified, and all address aspects of lifestyle, but only one, regarding cardiovascular prevention, highlights all six pillars. Despite this, a literature search involving over 50 articles showed that there is evidence that all the pillars can help control each of these NCDs. Conclusion: Rarely are the six pillars of lifestyle contemplated in Brazilian guidelines for AMI, DM, and COPD. The literature review identified evidence of all lifestyle pillars to offer a holistic approach for the management and prevention of NCDs.

Feasibility of physiological pacing rate in cardiac resynchronization therapy.

AIMS: Although cardiac resynchronization therapy (CRT) improves functional capacity in heart failure patients, a blunted heart rate (HR) response remains after treatment. So we aimed to evaluate the feasibility of the physiological pacing rate (PPR) in CRT patients. METHODS: A cohort of 30 clinical mildly symptomatic CRT patients underwent the six-minute walk test (6MWT). During the 6MWT, HR, blood pressure, and maximum walking distance were assessed. The measurements were obtained in a pre to post manner, with CRT at nominal settings and with the physiological phase (CRT PPR), in which HR was increased by 10% above the maximum HR achieved previously. The CRT cohort also comprised a matched control group (CRT CG). In the CRT CG, the 6MWT was repeated after the standard evaluation with no PPR. The evaluations were blinded for patients and for the 6MWT evaluator. RESULTS: During the 6MWT, CRT PPR led to an increase in walking distance of 40.5 m (9.2%; P < 0.0001) when compared with baseline trial. Additionally, CRT PPR increased the maximum walking distance compared with CRT CG 479.3 ± 68.9 m vs. 420.3 ± 44.8 m, respectively, P = 0.001. In the CRT CG, CRT PPR increased the variation in walking distance, compared with baseline trials, respectively 2.40 ± 3.8% vs. 9.25 ± 7.0%, P = 0.007. CONCLUSIONS: In mildly symptomatic CRT patients PPR is feasible, leading to improvements in functional capacity. In this regard, the efficacy of PPR must be confirmed by controlled randomized trials.

Acessibilidade do termo de consentimento na pesquisa clínica no Brasil / Accessibility of the consent form in Brazilian clinical research / Accesibilidad al formulario de consentimiento en la investigación clínica en Brasil

Resumo O termo de consentimento livre e esclarecido tem a função de informar o participante de pesquisas clínicas sobre a natureza da pesquisa e seus direitos, formalizando sua decisão de participar. Estudos indicam que esse documento é redigido de modo complexo, comprometendo a autonomia do participante. Para este trabalho, foram redigidos dois termos de consentimento da mesma pesquisa hipotética, com estilos de redação diferentes. Ambos os termos foram analisados pela ferramenta Coh-Metrix Port, que avalia métricas linguísticas e acessibilidade textual. A análise indicou que os textos são complexos e exigem alta escolaridade para serem entendidos. Esses achados reforçam a percepção de que, no Brasil, os termos de consentimento podem ter sua real função comprometida e apontam a importância de modificar sua forma de elaboração.

Abstract The informed consent form informs clinical research patients about the nature of the research and their rights, formalizing their decision to participate; however, studies show that this document is written in a complex manner, compromising patient autonomy. Two consent forms from the same hypothetical research were developed with different writing styles and analyzed by the Coh-Metrix Port tool, which evaluates linguistic metrics and textual accessibility. Results showed that both texts were complex and required high schooling level to be understood. These findings reinforce the perception that consent forms may have their real function compromised and point to the importance of changing its elaboration.

Resumen El formulario de consentimiento informado tiene la finalidad de mostrar la naturaleza de la investigación y sus derechos al participante de la investigación clínica para formalizar su decisión de participar en el estudio. Los estudios indican que la redacción de este documento es compleja, lo que compromete la autonomía del participante. Para este estudio se redactaron dos formularios de consentimiento de una misma investigación hipotética, con diferentes estilos de escritura. Para el análisis de ambos formularios se utilizó la herramienta Coh-Metrix Port, que evalúa las métricas lingüísticas y la accesibilidad textual. Los resultados apuntaron a que los textos son complejos, lo que requiere un alto nivel de educación para su comprensión. Estos hallazgos coinciden que, en Brasil, los formularios de consentimiento pueden tener su finalidad comprometida y señalan la necesidad de modificar su forma de elaboración.

Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms.

Chagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) ≥ 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.

DNA barcode reveals candidate species of Scinax and Ololygon (Anura: Hylidae) in Atlantic Forest.

Molecular species delimitation methods are efficient tools to identify species, including the discovery of new taxa and cryptic organisms, thus being useful to biodiversity studies. In the present work, 16S mitochondrial sequences and cytochrome oxidase I (COI) were used to evaluate the richness of species in the genus Scinax and Ololygon from a biodiversity hotspot in Atlantic Forest. A total of 109 specimens formally belonging to eight species of Scinax and three species of Ololygon were collected in 13 localities along the state of Bahia (northeastern Brazil) and one site in Espírito Santo (southeastern Brazil). Of the Scinax species collected in this study, three were morphologically differentiated from other described species and identified as putative new species (Scinax sp.1, Scinax sp.2 and Scinax sp.3). The species delimitations were inferred using three different methods: ABGD, PTP and mPTP which allowed recognizing 11 Scinax species and five Ololygon species. Scinax sp. 1, Scinax sp. 2 and Scinax sp. 3, have been confirmed as new putative species and Ololygon argyreornata possibly contains cryptic species. We suggest additional studies, including morphological and bioacoustic data to validate these new putative species.

Myocardial function reclassification: Echocardiographic strain patterns in patients with chronic Chagas cardiomyopathy and intraventricular dyssynchrony.

BACKGROUND: We aimed to identify, among Chronic Chagas Cardiomyopathy (CCC) patients with left ventricular dysfunction (LVD) and non-left bundle branch block (non-LBBB), subgroups with different functional and mechanical patterns of global longitudinal strain (GLS) and intraventricular dyssynchrony (IVD) at rest and after exercise stress test, and reclassify them using a new echocardiographic approach. METHODOLOGY: In this single-center cross-sectional study, 40 patients with CCC, left ventricular ejection fraction (LVEF) ≤ 35% and non-LBBB underwent rest echocardiography and then treadmill exercise stress echocardiography with GLS and IVD analysis. The sample was divided into four groups, based on GLS and IVD significant variation between rest and exercise: GLS + IVD+ (9 patients); GLS + IVD- (9 patients); GLS-IVD+ (10 patients); GLS-IVD- (10 patients). RESULTS: At rest, median LVEF was 28% (21.3%-33%) and GLS (-7% (-5%/-9.3%), were not different among groups. The average response of GLS was an increase of 0.74% over rest values, and the average response of IVD was a decrease of 6.9 ms. Group GLS-IVD+ presented more dyssynchrony at rest (p = 0.01). Left atrial (LA) volume (higher in GLS-IVD-) (p = 0.022) and TAPSE (higher in GLS + IVD+) (p = 0.015) were also different among groups at baseline. Of the 40 patients evaluated, 27 (67.5%) had very severe LVD (GLS < -8%). In addition, among these patients, 11 patients had contractile reserve after undergoing stress echocardiography. CONCLUSIONS: In patients with CCC, severe LVD and non-LBBB, the evaluation of GLS and IVD between rest and exercise was able to reclassify myocardial function and to identify subgroups with contractile reserve and significant dyssynchronopathy.

Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms.

The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain-Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.

Perspectivas bioéticas sobre tomada de decisão em tempos de pandemia / Bioethical perspectives on decision-making in times of pandemic / Perspectivas bioéticas sobre la toma de decisiones en tiempos de pandemia

Resumo Este artigo busca identificar contribuições da bioética para enfrentar conflitos relacionados à tomada de decisão em tempos de pandemia. Trata-se de texto elaborado a partir de reflexões pessoais dos autores em diálogo com a literatura de diferentes perspectivas da bioética. Com fundamento em relatos históricos, argumenta-se que, durante epidemias, a sociedade passa a atuar em modo de excepcionalidade, o que exige argumentação mais apurada para se posicionar ante os conflitos que surgem. Analisam-se então diferentes vertentes teóricas - principialismo, personalismo, utilitarismo e bioética social -, recolhendo de cada uma elementos que podem nortear a tomada de decisão. Com base nessas contribuições, propõem-se parâmetros para a atuação dos profissionais da saúde, reconhecendo igual valor em cada vida humana, com o propósito de salvar o maior número de pessoas possível. Por fim, aponta-se para a responsabilidade de agentes políticos.

Abstract This article aims to identify the contribution of bioethics to resolve decision-making conflicts in healthcare in times of pandemic. The research was based on the authors' personal reflections in a dialogue with the literature and different bioethical perspectives. Historical accounts show that when a society is experiencing an epidemic it starts to function in a mode of social exceptionality, reinforcing the need for a more appropriate form of reasoning before the ethical conflicts that may arise from this situation. Some approaches to bioethics - principlism, personalism, utilitarianism and social bioethics - are briefly examined in order to obtain the elements for guiding the decision-making process. Finally, we suggest some parameters for health professionals, recognizing the value of all human lives, to save as many lives as possible.

Resumen Este artículo tiene como objetivo identificar la contribución de la bioética para hacer frente a los conflictos relacionados con la toma de decisiones en tiempos de pandemia. Se trata de un texto elaborado con base en las reflexiones personales de los autores en diálogo con la literatura de diferentes perspectivas de la bioética. Con base en los relatos históricos, se argumenta que, durante epidemias, la sociedad pasa a actuar en modo de excepcionalidad, lo que requiere una argumentación más precisa para posicionarse ante los conflictos que surgen. Se analizan entonces diferentes vertientes teóricas -el principialismo, el personalismo, el utilitarismo y la bioética social-, recogiendo de cada una los elementos que pueden orientar la toma de decisiones. Con base en dichas contribuciones, se proponen parámetros para la actuación de los profesionales de la salud, reconociendo el mismo valor en cada vida humana, con el propósito de salvar al mayor número posible de personas. Por fin, se apunta hacia la responsabilidad de los agentes políticos.

Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review.

The SARS-CoV-2 outbreak originally appeared in China in December 2019 and became a global pandemic in March 2020. This infectious disease has directly affected public health and the world economy. Several palliative therapeutic treatments and prophylaxis strategies have been used to control the progress of this viral infection, including pre-(PrEP) and post-exposure prophylaxis. On the other hand, research groups around the world are still studying novel drug prophylaxis and treatment using repurposing approaches, as well as vaccination options, which are in different pre-clinical and clinical testing phases. This systematic review evaluated 1,228 articles from the PubMed and Scopus indexing databases, following the Kitchenham bibliographic searching protocol, with the aim to list drug candidates, potentially approved to be used as new options for SARS-CoV-2 prophylaxis clinical trials and medical protocols. In searching protocol, we used the following keywords: "Covid-19 or SARS-CoV-2" or "Coronavirus or 2019 nCoV," "prophylaxis," "prophylactic," "pre-exposure," "COVID-19 or SARS-CoV-2 Chemoprophylaxis," "repurposed," "strategies," "clinical," "trials," "anti-SARS-CoV-2," "anti-covid-19," "Antiviral," "Therapy prevention in vitro," in cells "and" human testing. After all protocol steps, we selected 60 articles that included: 15 studies with clinical data, 22 studies that used in vitro experiments, seven studies using animal models, and 18 studies performed with in silico experiments. Additionally, we included more 22 compounds between FDA approved drugs and drug-like like molecules, which were tested in large-scale screenings, as well as those repurposed approved drugs with new mechanism of actions. The drugs selected in this review can assist clinical studies and medical guidelines on the rational repurposing of known antiviral drugs for COVID-19 prophylaxis.

Cardiac resynchronization therapy restores muscular metaboreflex control.

INTRODUCTION: The muscular metaboreflex, whose activation regulates blood flow during isometric and aerobic exercise, is blunted in patients with heart failure (HF), and cardiac resynchronization therapy (CRT) may restore this regulatory reflex. OBJECTIVE: To evaluate metaboreflex responses after CRT. METHODS: Thirteen HF patients and 12 age-matched healthy control subjects underwent the following evaluations (pre- and post-CRT implantation in the patient group): (a) heart rate, blood pressure, and forearm blood flow measurements; (b) muscle sympathetic nerve activity (MSNA) evaluation; and (c) peak oxygen consumption (VO2peak ). Examinations were performed at rest, during moderate isometric exercise (IE), and during forearm ischemia (metaboreflex activation). The primary outcome was the increment in MSNA during limb ischemia compared to the rest moment (ΔMSNA rest to metaboreflex activation). RESULTS: After CRT, rest MSNA decreased in the HF participants: 50.4 ± 9.2 bursts/min pre-CRT vs 34.0 ± 14.4 bursts/min post-CRT, P = .001, accompanied by an improvement in systolic blood pressure and in rate-pressure product. MSNA during limb ischemia decreased: 56.6 ± 11.5 bursts/min pre-CRT vs 43.6 ± 12.7 bursts/min post-CRT, P = .001, and the ΔMSNA rest to metaboreflex activation increased: 0% (interquartile range [IQR)], -7 to 9) vs 13% (IQR, 5-30), P = .03. An augmentation of mean blood pressure during limb ischemia post-CRT was noticed: 94 mmHg (IQR, 81-104) vs 110 mmHg (IQR, 100-117), P = .04. CRT improved VO2peak , and this improvement was correlated with diminution in ΔMSNA pre- to post-CRT at rest moment (rs = -0.74, P = .006). CONCLUSION: CRT provides metaboreflex sensitization and MSNA enhancement. The restoration of sympathetic responsiveness correlates with the improvement in functional capacity.

Effect of chronic kidney disease in ischemic cardiomyopathy: Long-term follow-up - REVISION-DM2 trial.

A strong association exists between chronic kidney disease (CKD) and coronary artery disease (CAD). The role of CKD in the long-term prognosis of CAD patients with versus those without CKD is unknown. This study investigated whether CKD affects ventricular function.From January 2009 to January 2010, 918 consecutive patients were selected from an outpatient database. Patients had undergone percutaneous, surgical, or clinical treatment and were followed until May 2015.In patients with preserved renal function (n = 405), 73 events (18%) occurred, but 108 events (21.1%) occurred among those with CKD (n = 513) (P < .001). Regarding left ventricular ejection fraction (LVEF) <50%, we found 84 events (21.5%) in CKD patients and 12 (11.8%) in those with preserved renal function (P < .001). The presence of LVEF <50% brought about a modification effect. Death occurred in 22 (5.4%) patients with preserved renal function and in 73 (14.2%) with CKD (P < .001). In subjects with LVEF <50%, 66 deaths (16.9%) occurred in CKD patients and 7 (6.9%) in those with preserved renal function (P = .001). No differences were found in CKD strata regarding events or overall death among those with preserved LVEF. In a multivariate model, creatinine clearance remained an independent predictor of death (P < .001).We found no deleterious effects of CKD in patients with CAD when ventricular function was preserved. However, there was a worse prognosis in patients with CKD and ventricular dysfunction.Resgistry number is ISRCTN17786790 at https://doi.org/10.1186/ISRCTN17786790.

Surgical reconstruction of the interdental papilla: 2 case reports.

The loss of interdental papillae may create esthetic and phonetic problems and facilitates food impaction. Nonsurgical and surgical approaches can be developed to restore these areas, depending on the amount of tissue lost. Periodontal surgical techniques are difficult to perform in the interdental space because of the limited amount of tissue and poor blood supply. The aim of this article is to describe a periodontal plastic surgical technique in which subepithelial connective tissue grafts associated with composite restorations are used to reconstruct interdental papillae. This approach was followed in 2 patients whose grafts were obtained from different donor sites: the palate and the retromolar tuberosity. The 12-month recall examinations of both patients revealed satisfactory results, including stable gingival margins and complete, harmonious fill of the interdental papillary areas.

A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy.

Aims: Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. Methods and results: This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. Conclusion: This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.

Impact of diabetes mellitus on ischemic cardiomyopathy. Five-year follow-up. REVISION-DM trial.

BACKGROUND: Patients with ischemic cardiomyopathy and severe left ventricular dysfunction have a worse survival prognosis than patients with preserved ventricular function. The role of diabetes in the long-term prognosis of this patient group is unknown. This study investigated whether the presence of diabetes has a long-term impact on left ventricular function. METHODS: Patients with coronary artery disease who underwent coronary artery bypass graft surgery, percutaneous coronary intervention, or medical therapy alone were included. All patients had multivessel disease and left ventricular ejection fraction measurements. Overall mortality, nonfatal myocardial infarction, stroke, and additional interventions were investigated. RESULTS: From January 2009 to January 2010, 918 consecutive patients were selected and followed until May 2015. They were separated into 4 groups: G1, 266 patients with diabetes and ventricular dysfunction; G2, 213 patients with diabetes without ventricular dysfunction; G3, 213 patients without diabetes and ventricular dysfunction; and G4, 226 patients without diabetes but with ventricular dysfunction. Groups 1, 2, 3, and 4, respectively, had a mortality rate of 21.6, 6.1, 4.2, and 10.6% (P < .001); nonfatal myocardial infarction of 5.3, .5, 7.0, and 2.6% (P < .001); stroke of .40, .45, .90, and .90% (P = NS); and additional intervention of 3.8, 11.7, 10.3, and 2.6% (P < .001). CONCLUSION: In this sample, regardless of the treatment previously received patients with or without diabetes and preserved ventricular function experienced similar outcomes. However, patients with ventricular dysfunction had a worse prognosis compared with those with normal ventricular function; patients with diabetes had greater mortality than patients without diabetes.Trial registration http://www.controlled-trials.com. Registration Number: ISRCTN66068876.

Predictors of death in chronic Chagas cardiomyopathy patients with pacemaker.

BACKGROUND: Chronic Chagas cardiomyopathy (CCC) is the most serious and frequent manifestation of Chagas disease. Conduction abnormalities and bradycardia requiring pacemaker are common. The aim of this study was to determine the rate and predictors of death in CCC patients with pacemaker. METHODS: In this single-center prospective cohort study we assessed the outcome of 396 CCC patients with pacemaker, followed-up for at least 24months. All patients underwent a clinical and device assessment, 12-lead electrocardiography and echocardiography. RESULTS: During the median follow-up of 1.9years (Interquartile range 1.6-2.4), there were 65 (16.4%) deaths, yielding an annual mortality rate of 8.6%. The major cause was sudden death (33.8%), followed by heart failure (HF), 32.3%. All the investigated variables were examined as potential predictors of death. The final multivariate logistic regression model included five independent variables: advanced HF functional class (OR [odds ratio] 6.71; 95% confidence interval [95% CI] 1.95-23.2; P=0.003), renal disease (OR 5.71; 95% CI 1.80-18.0; P=0.003), QRS ≥150ms (OR 2.80; 95% CI 1.08-7.27; P=0.034), left atrial enlargement (OR 2.75; 95% CI 1.09-6.95; P=0.032) and left ventricular ejection fraction ≤43% (OR 2.31; 95% CI 1.07-4.97; P=0.032). The model had good discrimination, confirmed by bootstrap validation (optimism-adjusted c-statistic of 0.78) and the calibration curve showed a proper calibration (slope=0.972). CONCLUSIONS: CCC patients with pacemaker have a high annual mortality rate despite that the pacemaker related variables were not predictors of death. The independent predictors of death can help us to identify the poor prognosis patients.