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.

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.

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.

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.

Genetic analysis reveals candidate species in the Scinax catharinae clade (Amphibia: Anura) from Central Brazil.

Scinax (Anura: Hylidae) is a species-rich genus of amphibians (113 spp.), divided into five species groups by morphological features. Cladistic analyses however revealed only two monophyletic clades in these groups: Scinax catharinae and Scinax ruber. Most species from the S. catharinae clade are found in Atlantic rainforest, except for Scinax canastrensis,S. centralis, S. luizotavioi, S. machadoi,S. pombali and S. skaios. In the present work, specimens of Scinax collected in Chapada dos Guimarães, central Brazil, were morphologically compatible with species from theS. catharinae group. On the other hand, genetic analysis based on mitochondrial (16S and 12S) and nuclear (rhodopsin) sequences revealed a nucleotide divergence of 6 to 20% between Scinax sp. and other congeners from the Brazilian savannah (Cerrado). Accordingly, Bayesian inference placed Scinax sp. in the S. catharinae clade with high support values. Hence, these findings strongly indicate the presence of a new species in the S. catharinae clade from the southwestern portion of the Brazilian savannah. To be properly validated as a novel species, detailed comparative morphological and bioacustic studies with other taxa from Brazil such asS. canastrensis, S. centralis, S. luizotavioi, S. machadoi, S. pombali and S. skaios are required.

Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease.

BACKGROUND: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. METHODS AND RESULTS: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. CONCLUSIONS: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.

Cytogenetic studies in six species of Scinax (Anura, Hylidae) clade Scinax ruber from northern and northeastern Brazil.

Scinax species are still underrepresented in cytogenetic studies, mainly with respect to populations from northeastern and northern Brazil. In this study, we provide new chromosomal information on Scinax boesemani, S. camposseabrai, S. garbei, S. pachycrus, S. trilineatus and S. x-signatus, all belonging to clade S. ruber. They were collected at two locations in the Caatinga biome (northeastern Brazil) and at one in the Amazon (northern Brazil) biomes. Chromosomes were analyzed by conventional staining, C-banding, Ag-NOR staining, and fluorochrome staining. All species shared a modal diploid value of 2n = 24 and fundamental arm number (FN) of 48. Moreover, both chromosomal size and morphology were similar to other species in this Scinaxclade. C-banding revealed centromeric heterochromatin in all species, along with terminal species-specific C-bands in some species. Active nucleolar organizer regions (Ag-NORs) were identified at 11q in most species, except for S. boesemani and S. garbei (Ag-NORs at interstitial region of 8q). Differing from most anurans, GC-rich regions were not restricted to NORs, but also coincident with some centromeric and terminal C-bands. These data contribute to the cytotaxonomy of Scinax by providing chromosomal markers and demonstrating the occurrence of microstructural rearrangements and inversions on chromosomal evolution of Scinax.

Maintenance periodontal therapy after systemic antibiotic and regenerative therapy of generalized aggressive periodontitis. A case report with 10-year follow-up.

Aggressive periodontitis (AgP) is an inflammatory disease characterized by rapid attachment loss and bone destruction. This case report presents the 10-year results in a subject with generalized AgP treated by a regenerative periodontal therapeutic approach and the adjunctive use of antibiotics, following a systematic maintenance periodontal therapy. The use of enamel matrix derivatives (EMD) and adjunctive antibiotic therapy to treat AgP yielded improvements in clinical parameters and radiographic bony fill. This combined therapeutic approach following a systematic supportive periodontal therapy supports the long-term maintenance of teeth with previous advanced periodontal defects, demonstrating successful stability after 10-years follow-up. Clinical Relevance: The combined treatment protocol using EMD plus adjunctive antibiotic therapy, associated with a systematic supportive periodontal therapy, benefits the long-term maintenance of teeth with previous advanced periodontal defects in subjects presenting AgP, supporting this approach as an alternative in the treatment of AgP.

Effects of cardiac resynchronization therapy on muscle sympathetic nerve activity.

INTRODUCTION: Muscle sympathetic nerve activity (MSNA) is an independent prognostic marker in patients with heart failure (HF). Therefore, its relevance to the treatment of HF patients is unquestionable. OBJECTIVES: In this study, we investigated the effects of cardiac resynchronization therapy (CRT) on MSNA response at rest and during exercise in patients with advanced HF. METHODS: We assessed 11 HF patients (51 ± 3.4 years; New York Heart Association class III-IV; left ventricular ejection fraction 27.8 ± 2.2%; optimal medical therapy) submitted to CRT. Evaluations were made prior to and 3 months after CRT. MSNA was performed at rest and during moderate static exercise (handgrip). Peak oxygen consumption (VO2 ) was evaluated by means of cardiopulmonary exercise test. HF patients with advanced NYHA class without CRT and healthy individuals were also studied. RESULTS: CRT reduced MSNA at rest (48.9 ± 11.1 bursts/min vs 33.7 ± 15.3 bursts/min, P < 0.05) and during handgrip exercise (MSNA 62.3 ± 13.1 bursts/min vs 46.9 ± 14.3 bursts/min, P < 0.05). Among HF patients submitted to CRT, the peak VO2 increased (12.9 ± 2.8 mL/kg/min vs 16.5 ± 3.9 mL/kg/min, P < 0.05) and an inverse correlation between peak VO2 and resting MSNA (r = -0.74, P = 0.01) was observed. CONCLUSIONS: In patients with advanced HF and severe systolic dysfunction: (1) a significant reduction of MSNA (at rest and during handgrip) occurred after CRT, and this behavior was significantly superior to HF patients receiving only medical therapy; (2) MSNA reduction after CRT had an inverse correlation with O2 consumption outcomes.

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.

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.

CHronic use of Amiodarone aGAinSt Implantable cardioverter-defibrillator therapy for primary prevention of death in patients with Chagas cardiomyopathy Study: rationale and design of a randomized clinical trial.

BACKGROUND: The implantable cardioverter defibrillator (ICD) is better than antiarrhythmic drug therapy for the primary and secondary prevention of all-cause mortality and sudden cardiac death in patients with either coronary artery disease or idiopathic dilated cardiomyopathy. This study aims to assess whether the ICD also has this effect for primary prevention in chronic Chagas cardiomyopathy (CCC). METHODS: In this randomized (concealed allocation) open-label trial, we aim to enroll up to 1,100 patients with CCC, a Rassi risk score for death prediction of ≥10 points, and at least 1 episode of nonsustained ventricular tachycardia on a 24-hour Holter monitoring. Patients from 28 centers in Brazil will be randomly assigned in a 1:1 ratio to receive an ICD or amiodarone (600 mg/d for 10 days, then 200-400 mg/d until the end of the study). The randomization sequence will be generated by computer, and the members of the committees responsible for end point validation and data analysis will be blinded to study assignment. The primary end point is all-cause death, and enrolment will continue until 256 patients have reached this end point. Key secondary end points include cardiovascular death, sudden cardiac death, hospitalization for heart failure, and quality of life. We expect follow-up to last 3 to 6 years, and data analysis will be done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov number NCT01722942. CONCLUSION: CHAGASICS is the first large-scale trial to assess the benefit of ICD therapy for the primary prevention of death in patients with CCC and nonsustained ventricular tachycardia, who have a moderate to high risk of death.

Cytogenetics and sperm ultrastructure of Atelopus spumarius (Anura, Bufonidae) from the Brazilian Amazon.

The current taxonomy of most Atelopus species is based on morphological and color data only. Recent studies suggest that A. spumarius may represent a species complex assigned under the same name. Karyotypic data and description of sperm ultrastructure for 13 specimens of A. spumarius are presented here for the first time. A chromosomal analysis revealed 2n = 22 chromosomes, with centromeric heterochromatin in all pairs and a nucleolar organizer region (NOR) on the telomere of pair 7. The sperm was of the bufonoid type, presenting a filiform nucleus covered by an acrosomal complex and a mitochondrial collar in the neck region. The tail was composed of an axoneme, an undulating membrane and an axial rod. A karyotype analysis of A. spumarius showed the same chromosome number and similar chromosomal morphology as described for congeneric species, with slight differences probably resulting from pericentric inversions. The NOR location (on pair 7) was the same as that observed for species belonging to the genus Rhinella. The spermatological findings indicate a close relationship between Atelopus and the bufonoid lineage. The present data are useful for reference in future studies to determine whether more than one species are assigned to A. spumarius.

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.

Sudden cardiac death in Brazil: study based on physicians' perceptions of the public health care system.

BACKGROUND: There are no available statistical data about sudden cardiac death in Brazil. Therefore, this study has been conducted to evaluate the incidence of sudden cardiac death in our population and its implications. METHODS: The research methodology was based on Thurstone's Law of Comparative Judgment, whose premise is that the more an A stimulus differs from a B stimulus, the greater will be the number of people who will perceive this difference. This technique allows an estimation of actual occurrences from subjective perceptions, when compared to official statistics. Data were collected through telephone interviews conducted with Primary and Secondary Care physicians of the Public Health Service in the Metropolitan Area of São Paulo (MASP). RESULTS: In the period from October 19, 2009, to October 28, 2009, 196 interviews were conducted. The incidence of 21,270 cases of sudden cardiac death per year was estimated by linear regression analysis of the physicians' responses and data from the Mortality Information System of the Brazilian Ministry of Health, with the following correlation and determination coefficients: r = 0.98 and r(2) = 0.95 (95% confidence interval 0.8-1.0, P < 0.05). The lack of waiting list for specialized care and socioadministrative problems were considered the main barriers to tertiary care access. CONCLUSIONS: The incidence of sudden cardiac death in the MASP is high, and it was estimated as being higher than all other causes of deaths; the extrapolation technique based on the physicians' perceptions was validated; and the most important bureaucratic barriers to patient referral to tertiary care have been identified. (PACE 2012; 35:1326-1331).

Cytogenetic analysis of two species in the Phyllomedusa hypochondrialis group (Anura, Hylidae).

The genus Phyllomedusa has been the target of regular taxonomic investigations. The species Phyllomedusa nordestina was recently separated from P. hypochondrialis. Morphological variations in the P. rohdei interpopulation have already been reported, suggesting the existence of more than one taxon under that name. In the present study, we have cytogenetically characterized two populations of P. nordestina and one of P. rohdei. Both species displayed 2n = 26 chromosomes with 12 metacentric, 12 submetacentric and 2 subtelocentric chromosomes. The C-banding analyses revealed discrete differences in the quantity of centromeric heterochromatin between the two species. The nucleolus organizer region (NOR) was detected in pair 9 of both species, but is located in the pericentromeric region of the short arm in P. nordestina and in the long arm subtelomeric region of P. rohdei. Chromosomal data from this study indicate karyotypic homeology between the two groups of P. hypochondrialis species and suggest the existence of more than one taxon under the P. rohdei name.

Ultimate ceramic veneer: a laboratory-guided preparation technique for minimally invasive laminate veneers.

Clinical success of ceramic laminate veneers depends on material selection, bonding procedures, controlled laboratory steps, and enamel preservation. Enamel preservation is the most critical because excessive tooth preparation can expose dentin reducing bond strength, which is a factor that can cause a decrease in long-term clinical success. The proposed technique based on carefully treatment planning developed between clinician and dental technician helps to maximize enamel preservation, which is an important element for clinical success.

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.

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.