Publications by authors named "Nadine Clausell"

105 Publications

Limited Predictive Role of the Revised Cardiac Risk Index in Kidney Transplant: Single Center Evaluation and Comparison With International Literature.

Curr Probl Cardiol 2021 Sep 30;46(9):100908. Epub 2021 May 30.

Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address:

Perioperative risk factors predicting major cardiovascular events (MACE) and the performance of the Revised Cardiac Risk Index (RCRI) in a retrospective cohort of 325 consecutive adult patients undergoing kidney transplant from deceased donor grafts were assessed. Primary outcome was a composite of MACE up to 30 days post-transplant. Incidence of MACE was 5.8% at 30 days. Overall proportion of patients with RCRI ≥ 4 was 5%, but was higher (28%) among those who developed MACE. Patients with RCRI ≥ 4 had lower survival free of MACE compared to those with RCRI < 4 (P <0.001); however, in multivariable analysis, RCRI was not a predictor of cardiovascular events. The RCRI demonstrated poor discrimination to predict MACE at 30 days [area under the curve 0.64 (95% CI 0.49-0.78)]. Revised Cardiac Risk Index was not associated with reduced MACE-free survival adjusted analysis and its predictive ability was poor.
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http://dx.doi.org/10.1016/j.cpcardiol.2021.100908DOI Listing
September 2021

Donor-recipient predicted heart mass ratio and right ventricular-pulmonary arterial coupling in heart transplant.

Eur J Cardiothorac Surg 2021 04;59(4):847-854

Graduate Studies Program on Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Objectives: Right ventricular-pulmonary arterial (RV-PA) coupling interactions are largely unexplored in heart transplant patients. The outcome of this study was RV-PA coupling at 7 and 30 days after heart transplant and its association with donor-recipient size matching.

Methods: Clinical, echocardiographic and haemodynamic data from a retrospective cohort of heart transplant recipients and respective donors were reviewed. Coupling between RV-PA was examined by assessing the RV fractional area change and pulmonary artery systolic pressure ratio. Donor-recipient size matching was assessed by the predicted heart mass (PHM) ratio, and groups with a PHM ratio <1 and ≥1 were compared.

Results: Forty-four heart transplant recipients were included in this study (50 years, 57% male sex). Postoperative RV-PA coupling improved from 7 to 30 days (RV fractional area change/pulmonary artery systolic pressure 0.9 ± 0.3 vs 1.2 ± 0.3; P < 0.001). A positive association was found between an adequate PHM ratio and improvement of RV fractional area change/pulmonary artery systolic pressure at 30 days, independent of graft ischaemic time and pre-existent pulmonary hypertension (B coefficient 0.54; 95% confidence interval 0.11-0.97; P = 0.016; adjusted R2 = 0.24).

Conclusions: These findings highlight the role of PHM as a metric to help donor selection and suggest its impact in RV-PA coupling interactions post-heart transplant.
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http://dx.doi.org/10.1093/ejcts/ezaa391DOI Listing
April 2021

Exercise training modalities for heart transplant recipients: a systematic review and network meta-analysis protocol.

BMJ Open 2020 12 29;10(12):e044975. Epub 2020 Dec 29.

Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Hospital das Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

Introduction: Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients.

Methods And Analysis: We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.gov and REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository.

Ethics And Dissemination: Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal.

Prospero Registration Number: CRD42020191192.
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http://dx.doi.org/10.1136/bmjopen-2020-044975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778772PMC
December 2020

Post Heart Transplantation Coronary Artery Fistula and Coronary Artery Aneurysm Successfully Managed With the Implantation of Covered Stents.

J Invasive Cardiol 2020 Jul;32(7):E191-E192

Schulich Medicine & Dentistry Western University, London Health Sciences Centre, St. Joseph's Health Care, London, Canada.

Coronary-to-cardiac chamber fistulae and coronary aneurysms are potential complications after heart transplantation. In the setting of exercise intolerance and large fistulae at major coronary vessels, covered stents may provide an effective interventional strategy.
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July 2020

A Comprehensive and Contemporary Review on Immunosuppression Therapy for Heart Transplantation.

Curr Pharm Des 2020 ;26(28):3351-3384

Post-graduation Program in Medical Science: Cardiology and Cardiovascular Science, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. However, there are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant morbidity and survival while preventing both rejection and complications of immunosuppression. The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches are provided. Cardiac allograft rejection classification and up-to-date management are summarized. Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression in heart transplantation are highlighted.
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http://dx.doi.org/10.2174/1381612826666200603130232DOI Listing
January 2021

Safety and Results of Bioelectrical Impedance Analysis in Patients with Cardiac Implantable Electronic Devices.

Braz J Cardiovasc Surg 2020 04 1;35(2):169-174. Epub 2020 Apr 1.

Hospital de Clínicas de Porto Alegre Porto Alegre RS Brazil Hospital de Clínicas de Porto Alegre - HCPA, Porto Alegre, RS, Brazil.

Objective: To analyze the dual interference between cardiac implantable electronic devices (CIEDs) and bioelectrical impedance analysis (BIA).

Methods: Forty-three individuals admitted for CIEDs implantation were submitted to a tetrapolar BIA with an alternating current at 800 microA and 50 kHz frequency before and after the devices' implantation. During BIA assessment, continuous telemetry was maintained between the device programmer and the CIEDs in order to look for evidence of possible electric interference in the intracavitary signal of the device.

Results: BIA in patients with CIEDs was safe and not associated with any device malfunction or electrical interference in the intracardiac electrogram of any electrode. After the implantation of the devices, there were significant reductions in BIA measurements of resistance, reactance, and measurements adjusted for height resistance and reactance, reflecting an increase (+ 1 kg; P<0.05) in results of total body water and extracellular water in liter and, consequently, increases in fat-free mass (FFM) and extracellular mass in kg. Because of changes in the hydration status and FFM values, without changes in weight, fat mass was significantly lower (-1.2 kg; P<0.05).

Conclusion: BIA assessment in patients with CIEDs was safe and not associated with any device malfunction. The differences in BIA parameters might have occurred because of modifications on the patients' body composition, associated to their hydration status, and not to the CIEDs.
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http://dx.doi.org/10.21470/1678-9741-2019-0098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199980PMC
April 2020

Cardiopulmonary exercise capacity and quality of life of patients with heart failure undergoing a functional training program: study protocol for a randomized clinical trial.

BMC Cardiovasc Disord 2020 04 25;20(1):200. Epub 2020 Apr 25.

Exercise Pathophysiology Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

Background: Exercise intolerance is a common finding in heart failure that generates a vicious cycle in which the individual starts to limit his activities even more due to progressive fatigue. Regular physical exercise can increase the cardiopulmonary exercise capacity of these individuals. A new approach to physical exercise, known as functional training, could improve the oxygen consumption and quality of life of patients with heart failure; however, there is no information about the effect of this modality of exercise in this patient population. This randomized trial will compare the effects of 36 sessions of functional training versus strength training in heart failure patients.

Methods: This randomized parallel-design examiner-blinded clinical trial includes individuals of both sexes aged ≥40 years receiving regular follow-up at a single academic hospital. Subjects will be randomly allocated to an intervention group (for 12-week functional training) or an active comparator group (for 12-week strength training). The primary outcomes will be the difference from baseline to the 3-month time point in peak oxygen consumption on cardiopulmonary exercise testing and quality of life assessed by the Minnesota Living with Heart Failure Questionnaire. Secondary outcome measures will include functionality assessed by the Duke Activity Status Index and gait speed test; peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively; endothelial function by brachial artery flow-mediated dilation; lean body mass by arm muscle circumference; and participant adherence to the exercise programs classified as a percentage of the prescribed exercise dose.

Discussion: The functional training program aims to improve the functional capacity of the individual using exercises that relate to his specific physical activity transferring gains effectively to one's daily life. In this context, we believe that that functional training can increase the cardiopulmonary exercise capacity and quality of life of patients with heart failure. The trial has been recruiting patients since October 2017.

Trial Registration: NCT03321682. Registered on October 26, 2017.
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http://dx.doi.org/10.1186/s12872-020-01481-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183632PMC
April 2020

Impaired Right Ventricular Function in Heart Transplant Rejection.

Arq Bras Cardiol 2020 04 14;114(4):638-644. Epub 2020 Feb 14.

PPG em Cardiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Background: The practice of screening for complications has provided high survival rates among heart transplantation (HTx) recipients.

Objectives: Our aim was to assess whether changes in left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) are associated with cellular rejection.

Methods: Patients who underwent HTx in a single center (2015 - 2016; n = 19) were included in this retrospective analysis. A total of 170 biopsies and corresponding echocardiograms were evaluated. Comparisons were made among biopsy/echocardiogram pairs with no or mild (0R/1R) evidence of cellular rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n=15). P-values < 0.05 were considered statistically significant Results: Most patients were women (58%) with 48 ± 12.4 years of age. Compared with echocardiograms from patients with 0R/1R rejection, those of patients with 2R biopsies showed greater LV posterior wall thickness, E/e' ratio, and E/A ratio compared to the other group. LV systolic function did not differ between groups. On the other hand, RV systolic function was more reduced in the 2R group than in the other group, when evaluated by TAPSE, S wave, and RV fractional area change (all p < 0.05). Furthermore, RV GLS (-23.0 ± 4.4% in the 0R/1R group vs. -20.6 ± 4.9% in the 2R group, p = 0.038) was more reduced in the 2R group than in the 0R/1R group.

Conclusion: In HTx recipients, moderate acute cellular rejection is associated with RV systolic dysfunction as evaluated by RV strain, as well as by conventional echocardiographic parameters. Several echocardiographic parameters may be used to screen for cellular rejection.
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http://dx.doi.org/10.36660/abc.20190054DOI Listing
April 2020

Expanding benefits from cardiac resynchronization therapy to exercise-induced left bundle branch block in advanced heart failure.

ESC Heart Fail 2020 02 10;7(1):329-333. Epub 2020 Jan 10.

Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rua Ramiro Barcelos, 2350, room 2060, Porto Alegre, RS, 90035-903, Brazil.

Indications of cardiac resynchronization therapy (CRT) do not include exercise-induced left bundle branch block, but functional impairment could be improved with CRT in such cases. A 57-year-old woman with idiopathic dilated cardiomyopathy (ejection fraction 23%) presented with New York Heart Association Class IV and recurrent hospitalizations. During heart transplant evaluation, a new onset of intermittent left bundle branch block was observed on the cardiopulmonary exercise test. CRT was implanted, and 97% resynchronization rate was achieved. In 12 month follow-up, both clinical and prognostic exercise parameters improved. In patients with heart failure with reduced ejection fraction and no left bundle branch block at rest, exercise test can uncover electromechanical dyssynchrony that may benefit from CRT.
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http://dx.doi.org/10.1002/ehf2.12580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083438PMC
February 2020

Continuous Intravenous Inotropes in Ward Units: Expanding Therapy Outside Intensive Care using a Safety-Oriented Protocol.

Arq Bras Cardiol 2019 06 6;112(5):573-576. Epub 2019 Jun 6.

Hospital de Clínicas de Porto Alegre, Porto Alegre, RS - Brazil.

Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.
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http://dx.doi.org/10.5935/abc.20190078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555580PMC
June 2019

Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system.

Am J Physiol Regul Integr Comp Physiol 2019 06 1;316(6):R776-R782. Epub 2019 May 1.

Experimental and Molecular Cardiovascular Laboratory and Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain β-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.
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http://dx.doi.org/10.1152/ajpregu.00205.2018DOI Listing
June 2019

Characterization of advanced glycation end products and their receptor (RAGE) in an animal model of myocardial infarction.

PLoS One 2019 11;14(1):e0209964. Epub 2019 Jan 11.

Cardiovascular Research Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.

Circulating advanced glycation end products (AGE) and their receptor, RAGE, are increased after a myocardial infarction (MI) episode and seem to be associated with worse prognosis in patients. Despite the increasing importance of these molecules in the course of cardiac diseases, they have never been characterized in an animal model of MI. Thus, the aim of this study was to characterize AGE formation and RAGE expression in plasma and cardiac tissue during cardiac remodeling after MI in rats. Adult male Wistar rats were randomized to receive sham surgery (n = 15) or MI induction (n = 14) by left anterior descending coronary artery ligation. The MI group was stratified into two subgroups based on postoperative left ventricular ejection fraction: low (MIlowEF) and intermediate (MIintermEF). Echocardiography findings and plasma levels of AGEs, protein carbonyl, and free amines were assessed at baseline and 2, 30, and 120 days postoperatively. At the end of follow-up, the heart was harvested for AGE and RAGE evaluation. No differences were observed in AGE formation in plasma, except for a decrease in absorbance in MIlowEF at the end of follow-up. A decrease in yellowish-brown AGEs in heart homogenate was found, which was confirmed by immunodetection of N-ε-carboxymethyl-lysine. No differences could be seen in plasma RAGE levels among the groups, despite an increase in MI groups over the time. However, MI animals presented an increase of 50% in heart RAGE at the end of the follow-up. Despite the inflammatory and oxidative profile of experimental MI in rats, there was no increase in plasma AGE or RAGE levels. However, AGE levels in cardiac tissue declined. Thus, we suggest that the rat MI model should be employed with caution when studying the AGE-RAGE signaling axis or anti-AGE drugs for not reflecting previous clinical findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209964PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329515PMC
September 2019

Heart Transplantation Cost Composition in Brazil: A Patient-Level Microcosting Analysis and Comparison With International Data.

J Card Fail 2018 Dec 26;24(12):860-863. Epub 2018 Oct 26.

Heart Transplant Program, Division of Cardiology, Hospital de Clínicas de Porto Alegre, Brazil; National Health Technology Assessment Institute, National Council for Scientific and Technological Development (CNPq), Brazil. Electronic address:

Background: Advanced heart failure (HF) therapies, such as heart transplantation, are resource intensive and costly. In Brazil, only one-fifth of the estimated population need is fulfilled. We examined cost expenditures of heart transplants in a public institution in Brazil.

Methods And Results: We used microcosting analysis (time-driven activity-based costing) to examine total costs and individual cost components related to the index transplant hospital admission of all consecutive heart transplant recipients at a single center from July 2015 to June 2017. Average total cost for the 27 patients included was US$ 74,341 which exceeds the reimbursement value per patient by 60%. Major cost drivers were hospital structure and personnel, similarly to what is observed in the United States (US) and other developed countries. Total costs for index transplant admission were ∼50% lower than in the US, but approximate to values reported in some European countries. Costs of heart transplantation in Brazil were lower than those reported for developed countries, and higher than national reimbursement values.

Conclusions: Advanced microcosting methodologies represent an important quality contribution to economic studies in health care and may provide insights for transplant-related health care policies in developing countries.
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http://dx.doi.org/10.1016/j.cardfail.2018.10.011DOI Listing
December 2018

Modified autotransplant with three-dimensional printing for treatment of primary cardiac sarcoma.

J Thorac Cardiovasc Surg 2019 02 25;157(2):e41-e43. Epub 2018 Sep 25.

Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2018.08.087DOI Listing
February 2019

Relationship of polymorphisms in the tissue inhibitor of metalloproteinase (TIMP)-1 and -2 genes with chronic heart failure.

Sci Rep 2018 06 21;8(1):9446. Epub 2018 Jun 21.

Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil (ULBRA), Canoas, 92425-900, Brazil.

Dysregulated expression of tissue inhibitors of matrix metalloproteinases (TIMPs) is associated with systolic dysfunction and worsening heart failure (HF). However, no study has assessed the relationship between TIMP polymorphisms and chronic HF. In this study, 300 HF outpatients with reduced left ventricular ejection fraction and 304 healthy blood donors were genotyped for the 372 T > C polymorphism (Phe124Phe; rs4898) in the TIMP-1 gene and the -418 G > C polymorphism (rs8179090) in the TIMP-2 gene to investigate whether these polymorphisms are associated with HF susceptibility and prognosis. The genotype and allele frequencies of the 372 T > C polymorphism in HF patients were not significantly different from those observed among healthy subjects, and the C allele of the -418 G > C polymorphism was very rare in our population (frequency < 1%). After a median follow-up duration of 5.5 years, 121 patients (40.3%) died (67 of them from HF). Survival analysis did not show statistically significant differences in all-cause death and HF-related death between patients with and without the T allele (P > 0.05 for all comparisons). Thus, our findings do not support the hypothesis that the 372 T > C (Phe124Phe) polymorphism in the TIMP-1 gene and the -418 G > C polymorphism in the TIMP-2 gene are associated with HF susceptibility and prognosis in Southern Brazilians.
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http://dx.doi.org/10.1038/s41598-018-27857-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013444PMC
June 2018

Phase angle and mortality: a systematic review.

Eur J Clin Nutr 2019 04 26;73(4):495-508. Epub 2018 Apr 26.

Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

Background/objectives: The phase angle, expressed through bioelectrical impedance, has been studied as a prognostic marker in several health conditions. As this issue is still conflicting, the question whether this parameter correlates with mortality in the most diverse clinical situations remains. Therefore, this study aimed to evaluate the relationship between phase angle and mortality through a systematic review of the literature.

Subjects/methods: This research was conducted in electronic databases (Pubmed, Embase, Cochrane, Lilacs, Scielo, e Scopus), and included studies that had phase angle as a variable of interest and mortality/survival as an outcome. Data were extracted independently by two reviewers and disagreements were assessed by a third reviewer.

Results: Forty-eight of 455 papers were assessed and an amount of 42 showed a correlation between phase angle and mortality.

Conclusions: Phase angle seems to be a good indicator for mortality in many clinical situations and can be used in screening individuals prone to this outcome.
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http://dx.doi.org/10.1038/s41430-018-0159-1DOI Listing
April 2019

Natriuretic Peptide and Clinical Evaluation in the Diagnosis of Heart Failure Hemodynamic Profile: Comparison with Tissue Doppler Echocardiography.

Arq Bras Cardiol 2018 Mar;110(3):270-277

Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Background: Physical examination and B-type natriuretic peptide (BNP) have been used to estimate hemodynamics and tailor therapy of acute decompensated heart failure (ADHF) patients. However, correlation between these parameters and left ventricular filling pressures is controversial.

Objective: This study was designed to evaluate the diagnostic accuracy of physical examination, chest radiography (CR) and BNP in estimating left atrial pressure (LAP) as assessed by tissue Doppler echocardiogram.

Methods: Patients admitted with ADHF were prospectively assessed. Diagnostic characteristics of physical signs of heart failure, CR and BNP in predicting elevation (> 15 mm Hg) of LAP, alone or combined, were calculated. Spearman test was used to analyze the correlation between non-normal distribution variables. The level of significance was 5%.

Results: Forty-three patients were included, with mean age of 69.9 ± 11.1years, left ventricular ejection fraction of 25 ± 8.0%, and BNP of 1057 ± 1024.21 pg/mL. Individually, all clinical, CR or BNP parameters had a poor performance in predicting LAP ≥ 15 mm Hg. A clinical score of congestion had the poorest performance [area under the receiver operating characteristic curve (AUC) 0.53], followed by clinical score + CR (AUC 0.60), clinical score + CR + BNP > 400 pg/mL (AUC 0.62), and clinical score + CR + BNP > 1000 pg/mL (AUC 0.66).

Conclusion: Physical examination, CR and BNP had a poor performance in predicting a LAP ≥ 15 mm Hg. Using these parameters alone or in combination may lead to inaccurate estimation of hemodynamics.
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http://dx.doi.org/10.5935/abc.20180046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898778PMC
March 2018

Low exertional inspiratory capacity is not related to dynamic inspiratory muscle weakness in heart failure.

Respir Physiol Neurobiol 2018 08 16;254:32-35. Epub 2018 Apr 16.

Universidade Federal do Rio Grande do Sul (UFRGS) & Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil. Electronic address:

Reduction in inspiratory capacity (IC) during exercise has been reported in chronic heart failure (CHF). Since inspiratory muscle dysfunction may be present to a variable degree, the assumption that IC reduction during exercise represents an increase in end-expiratory lung volume must be made with caution. This interpretation is flawed if patients develop dynamic inspiratory muscle strength reduction, i.e., progressively lower esophageal (Pes) pressures as the IC maneuvers are repeated. Sixteen CHF patients and 9 age-matched controls performed an incremental exercise test with serial IC and respiratory pressure measurements. Regardless whether IC decreased or not with exercise (N = 4 and N = 12, respectively), Pes,IC remained stable. This was confirmed by similar Pes,sniff immediately upon exercise cessation (p > .05). No association was found between changes in IC and related Pes from rest to peak exercise. Owing to the lack of dynamic inspiratory muscle weakness, non-invasive indexes of lung mechanics can be reliably obtained from exercise IC in CHF.
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http://dx.doi.org/10.1016/j.resp.2018.04.005DOI Listing
August 2018

Chronic painful oral ulcers in a heart transplant recipient.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 06 21;127(6):468-476. Epub 2018 Feb 21.

Department of Oral Medicine, Porto Alegre Clinics Hospital (HCPA/UFRGS), Porto Alegre, RS, Brazil; Department of Oral Pathology, Dental School, Federal University of Rio do Sul, Porto Alegre, RS, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.oooo.2018.01.026DOI Listing
June 2019

Characteristics associated with mortality in patients with chronic obstructive pulmonary disease (COPD)-heart failure coexistence.

Prim Health Care Res Dev 2018 11 21;19(6):570-574. Epub 2018 Feb 21.

1Hospital de Clinicas de Porto Alegre (HCPA),Universidade Federal do Rio Grande do Sul (UFRGS),Porto Alegre,RS,Brazil.

AimTo investigate if cardiac/pulmonary functional tests and variables obtained from clinical practice (body mass index, dyspnea, functional class, clinical judgment of disability to perform an exercise test and previous hospitalization rate) are related to mortality in patients with overlap chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). BACKGROUND: Although the coexistence of COPD and CHF has been growingly reported, description of survival predictors considering the presence of both conditions is still scarce. METHODS: Using a cohort design, outpatients with the previous diagnosis of COPD and/or CHF that performed both spirometry and echocardiography in the same year were followed-up during a mean of 20.9±8.5 months.FindingsOf the 550 patients initially evaluated, 301 had both spirometry and echocardiography: 160 (53%) with COPD on isolation; 100 (33%) with CHF on isolation; and 41 (14%) with overlap. All groups presented similar mortality: COPD 17/160 (11%); CHF 12/100 (12%); and overlap 7/41 (17%) (P=0.73). In the overlap group (n=41), inability to exercise and hospitalization rate were the unique parameters associated with higher mortality (seven events) in univariate analyses. In conclusion, inability to exercise and hospitalization rate emerged as the unique parameters associated with mortality in our sample.
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http://dx.doi.org/10.1017/S1463423618000117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692830PMC
November 2018

Plasma levels of microRNA-21, -126 and -423-5p alter during clinical improvement and are associated with the prognosis of acute heart failure.

Mol Med Rep 2018 Mar 15;17(3):4736-4746. Epub 2018 Jan 15.

Cardiovascular Experimental and Molecular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035‑903, Brazil.

MicroRNAs are associated with myocardial damage and heart failure (HF). The present study investigated whether the plasma levels of microRNA (miR)‑21, ‑126 and ‑423‑5p alter according to the (de)compensated state of patients with HF and are associated with all‑cause mortality. In 48 patients with HF admitted to the emergency room for an episode of acute decompensation, blood samples were collected to measure miR and B‑type natriuretic peptide levels within 24 h of hospital admission, at the time of hospital discharge, and a number of weeks post‑discharge (chronic stable compensated state). Levels of miR‑21, miR‑126 and miR‑423‑5p increased between admission and discharge, and decreased following clinical compensation. During follow‑up (up to 48 months), 38 patients (79%) were rehospitalized at least once and 21 patients (44%) succumbed. Patients who had increased levels of miR‑21 and miR‑126 at the time of clinical compensation exhibited better 24‑month survival and remained rehospitalization‑free for a longer period compared with those with low levels. Additionally, patients whose levels of miR‑423‑5p increased between admission and clinical compensation experienced fewer hospital readmissions in the 24 months following the time of clinical compensation compared with those who had decreased levels. It was concluded that the plasma levels of miR‑21, miR‑126 and miR‑423‑5p altered during clinical improvement and were associated with the prognosis of acute decompensated HF.
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http://dx.doi.org/10.3892/mmr.2018.8428DOI Listing
March 2018

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival.

PLoS One 2016 23;11(8):e0161666. Epub 2016 Aug 23.

Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.

Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285-0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365-1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248-1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161666PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995023PMC
July 2017

Association between Spirituality and Adherence to Management in Outpatients with Heart Failure.

Arq Bras Cardiol 2016 Jun 17;106(6):491-501. Epub 2016 May 17.

Division of Cardiology, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Background: Spirituality may influence how patients cope with their illness.

Objectives: We assessed whether spirituality may influence adherence to management of outpatients with heart failure.

Methods: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence.

Results: One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments.

Conclusion: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient's care may lead to an improvement in adherence patterns in the complex heart failure management.
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http://dx.doi.org/10.5935/abc.20160076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940148PMC
June 2016

Prognostic role of phase angle in hospitalized patients with acute decompensated heart failure.

Clin Nutr 2016 12 13;35(6):1530-1534. Epub 2016 Apr 13.

Post-Graduate Program in Cardiovascular Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Ramiro Barcelos Street, 2400, Zip Code: 90035-003, Porto Alegre, Brazil; Hospital de Clínicas de Porto Alegre, Ramiro Barcelos Street, 2350, Zip Code: 90035-003, Porto Alegre, Brazil; Department of Internal Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, Ramiro Barcelos Street, 2400, Zip Code: 90035-003, Porto Alegre, Brazil. Electronic address:

Background & Aims: Patients with acute decompensated heart failure (ADHF) have exacerbation of symptoms and fluid retention, and high risk of re-hospitalizations and mortality. The aim of this study was to evaluate the role of phase angle at hospital admission as a prognostic marker of mortality in patients with ADHF.

Methods: Patients hospitalized for ADHF, with left ventricular ejection fraction (LVEF) <45% and BOSTON criteria ≥8 points were included. The patients were evaluated at hospital admission (first 36 h) and then followed up for assessment of outcomes. Phase angle was measured with tetra polar bioelectrical impedance device. Mortality data was obtained from an average of 24 months after discharge, from the medical records of the hospital and outpatient or telephone contact with patients or family members. The best-discriminatory level of phase angle was selected based on the ROC curve for mortality.

Results: Seventy-one patients were included and the majority was male (63%), with a mean age of 61 ± 12 years, ischemic etiology being the most prevalent (48%) and LVEF average of 26 ± 8%. Mortality was 49% at an average of 24 months after hospital discharge. The average phase angle at hospital admission was 5.6 ± 2°, and lower values were associated with higher mortality. Survivors were compared to died patients in the risk factor variables for mortality. In multivariate analysis adjusting for age, LVEF and urea, phase angle <4.8° was independently associated with increased mortality (HR 2.67; p = 0.015).

Conclusions: Phase angle seems to be a prognostic marker in patients with ADHF independently of other known risk factors.
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http://dx.doi.org/10.1016/j.clnu.2016.04.007DOI Listing
December 2016

Geographic Differences in Patients in a Global Acute Heart Failure Clinical Trial (from the ASCEND-HF Trial).

Am J Cardiol 2016 Jun 19;117(11):1771-8. Epub 2016 Mar 19.

Duke Clinical Research Institute, Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.

A growing number of countries and geographical regions are involved in major clinical trials. Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure is the largest trial in acutely decompensated heart failure (HF) with patients from 5 geographical regions: North America (NA), Latin America (LA), Western Europe (WE), Central Europe (CE), and Asia-Pacific (AP). Data from the 5 geographical areas were compared including baseline characteristics, medications, 30-day outcomes (mortality and mortality or HF hospitalization), and 180-day mortality. Of the 7,141 study patients, 3,243 (45.4%) were from NA (average of 15.2 patients/site), 1,762 (24.7%) from AP (28.4 patients/site), 967 (13.5%) from CE (20.2 patients/site), 665 (9.3%) from LA (17.1 patients/site), and 504 (7.1%) from WE (14.4 patients/site). There were marked differences in co-morbidities, clinical profile, medication use, length of stay, 30-day event rates, and 180-day mortality by region. Compared with NA, the adjusted risk for death or HF hospitalization at 30 days was significantly lower in CE (odds ratio [OR] 0.46, 95% CI 0.33 to 0.64), WE (OR 0.52 95% CI 0.35 to 0.75), and AP (OR 0.62 95% CI 0.48 to 0.79) and numerically lower in LA (OR 0.77, 95% CI 0.57 to 1.04) with similar results for 180-day mortality. In conclusion, in patients with acutely decompensated HF, major differences in baseline characteristics, treatments, length of the hospital stay, and 30-day HF rehospitalization rates, and 180-day mortality were found in patients enrolled from different geographical areas.
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http://dx.doi.org/10.1016/j.amjcard.2016.03.002DOI Listing
June 2016
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