Publications by authors named "Meliza Goi Roscani"

26 Publications

  • Page 1 of 1

Noninvasive ventilation can modulate heart rate variability during high-intensity exercise in COPD-CHF patients.

Heart Lung 2021 Jun 1;50(5):609-614. Epub 2021 Jun 1.

Cardiopulmonary Physiotherapy Laboratory, Physiotherapy Department, Federal University of Sao Carlos, UFSCar, Rodovia Washington Luis, KM 235, Monjolinho, CEP: 13565-905, Sao Carlos, SP, Brazil. Electronic address:

Objective: to assess the acute effects of non-invasive ventilation (NIV) during high-intensity exercise on heart rate variability (HRV) responses in chronic obstructive pulmonary disease (COPD) and Chronic heart failure (CHF) patients.

Methods: This was randomized, double blinded and controlled study. Fourteen patients with COPD-HF diagnosis were evaluated. The subjects underwent to the following tests: (I) cardiopulmonary exercise testing (CPET) on a cycle ergometer ramp protocol; (II) 7 days after CPET, patients randomly underwent two constant-load exercise (CLE) with NIV or Sham ventilation until tolerance limit, with 80% of the CPET peak load. R-R intervals (RRi) were continuously collected during rest, exercise and in recovery. Time and frequency domain and nonlinear heart rate variability (HRV) indices were obtained.

Results: NIV resulted in a decrease of Mean iRR, square root of the mean squared differences of successive RRi (rMSSD), RR tri index and high-frequency (HF), nu (p < 0.05) and increase of Mean HR, low-frequency (LF), nu and LF/HF (p < 0.05) during exercise when compared to rest. In addition, NIV during exercise induced lower rMSSD and Sample Entropy when compared with Sham (p < 0.05). Negative correlation was found between forced expiratory volume in 1 second (FEV L) vs HF (nu) during exercise with NIV (p = 0.04; r= -0.58). Furthermore, simple linear regression showed that the FEV (L) affected 30% of the HF (nu) response during the exercise with NIV.

Conclusion: NIV during exercise produced enhanced heart rate and autonomic responses in COPD-CHF patients. Additionally, COPD severity is negatively associated with a higher vagal response during exercise with NIV.
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http://dx.doi.org/10.1016/j.hrtlng.2021.04.004DOI Listing
June 2021

Cardiovascular benefits of a home-based exercise program in patients with sickle cell disease.

PLoS One 2021 12;16(5):e0250128. Epub 2021 May 12.

Department of Internal Medicine, Sao Paulo State University Julio de Mesquita Filho-Unesp, Botucatu, Sao Paulo, Brazil.

Background: Physical inactivity is an important risk factor for cardiovascular disease. The benefits of exercise in patients with chronic diseases, including cardiovascular diseases, are well established. For patients with sickle cell disease, medical recommendation was to avoid physical exercise for fear of triggering painful crises or increasing the impairment of the cardiopulmonary function. Only recently, studies have shown safety in exercise programs for this population. Despite that, there is no report that assess the effects of physical exercise on cardiac parameters in patients with sickle cell disease.

Objective: This study aimed to evaluate the impact of regular physical exercise (a home-based program) on cardiovascular function in patients with sickle cell disease.

Design: A quasi-randomized prospective controlled trial.

Setting: During the years 2015 and 2016, we started recruiting among adult patients treated at a Brazilian Center for Patients with Sickle Cell Disease to participate in a study involving a home exercise program. The experimental (exercise) and control groups were submitted to clinical evaluation and cardiovascular tests before and after the intervention. Analysis of variance was applied to compare groups, considering time and group factors.

Participants: Twenty-seven adult outpatients with a sickle cell disease diagnosis.

Interventions: Exercise group (N = 14): a regular home-based aerobic exercise program, three to five times per week not exceeding give times per week, for eight weeks; no prescription for the control group (N = 13).

Main Outcome Measures: Echocardiographic and treadmill test parameters.

Results: The exercise group showed significant improvement in cardiovascular tests, demonstrated by increased distance traveled on a treadmill (p<0.01), increased ejection fraction (p < 0.01) and improvement of diastolic function assessed by mitral tissue Doppler E' wave on echocardiography (p = 0.04). None of the patients presented a sickle cell crisis or worsening of symptoms during the exercise program.

Conclusion: The selected home-based exercise program is safe, feasible, and promotes a favorable impact on functional capacity and cardiovascular function in sickle cell disease patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250128PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115779PMC
May 2021

Use of ivermectin in the treatment of Covid-19: A pilot trial.

Toxicol Rep 2021 9;8:505-510. Epub 2021 Mar 9.

Department of Medicine, Federal University of São Carlos (UFSCar), 13565-905, São Carlos, São Paulo, Brazil.

Objectives: In this randomized open-label trial pilot study we assessed the antiviral effects and safety of various doses of ivermectin in patients with mild clinical symptoms of COVID-19.

Methods: Patients were randomly assigned to receive standard of care (SOC) treatment at hospital admission; SOC plus ivermectin 100 mcg/kg; SOC plus ivermectin 200 mcg/kg; or SOC plus ivermectin 400 mcg/kg. The primary assessed endpoint was the proportion of patients who achieved two consecutive negative SARS-CoV-2 RT PCR tests within 7 days of the start of the dosing period. This study was registered at ClinicalTrials.gov (NCT04431466).

Results: A total of 32 patients were enrolled and randomized to treatment. SOC treatment together with ivermectin did not result in any serious adverse events. All patients exhibited a reduction in SARS-CoV-2 viral load within 7 days; however, those who received ivermectin had a more consistent decrease as compared to the SOC alone group, characterized by a shorter time for obtaining two consecutive negative SARS-CoV-2 RT PCR tests.

Conclusions: Ivermectin is safe in patients with SARS-CoV-2, reducing symptomatology and the SARS-CoV-2 viral load. This antiviral effect appears to depend on the dose used, and if confirmed in future studies, it suggests that ivermectin may be a useful adjuvant to the SOC treatment in patients with mild COVID-19 symptoms.
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http://dx.doi.org/10.1016/j.toxrep.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942165PMC
March 2021

Association Between the Predictors of Functional Capacity and Heart Rate Off-Kinetics in Patients with Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 12;15:1977-1986. Epub 2020 Aug 12.

Cardiopulmonary Physiotherapy Laboratory, Physiotherapy Department, Federal University of Sao Carlos, Sao Paulo, Brazil.

Background: The heart rate (HR) kinetics as well as other predictors of functional capacity such as the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT), the Duke Activity Status Index (DASI) and the handgrip strength (HGS) represent important tools in assessing the impact of COPD on exercise performance and health status of individuals with COPD.

Purpose: To verify the relationship between functional capacity, measured using the six-minute walking test (6MWT), with the HR off-kinetics, HGS and the DASI and CAT scores.

Methods: For this cross-sectional study, 29 subjects with COPD underwent body composition, pulmonary function and cardiac function tests. Subsequently, the DASI and CAT questionnaires and HGS test were performed. The beat-to-beat R-R intervals (IRR) were collected in rest, during the test and in recovery after the 6MWT. The HR off-kinetics was obtained during a 360-second period in post-exercise recovery through the HR mono-exponential decay.

Results: Moderate correlations were observed between: 1) walked distance (WD) in the 6MWT and the CAT and DASI scores (r= -0.58, p=0.001 and r= 0.58, p=0.001, respectively); 2) WD and HGS (r=0.37, p=0.05); 3) and WD and HR off-kinetics (τ; r= -0.54, p=0.002 and MRT; r= -0.55, p=0.002, respectively).

Conclusion: The 6MWT performance is a direct measurement to evaluate functional capacity. Additionally, it is related to other direct and indirect markers for functional evaluation in patients with COPD. These results suggest the application of these tools in clinical practice, based on the accessibility, non-invasive character and easy applicability of these methods.
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http://dx.doi.org/10.2147/COPD.S260284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438181PMC
August 2020

Left Ventricular Geometry in COPD Patients: ARE THERE ASSOCIATIONS WITH AIRFLOW LIMITATION, FUNCTIONAL CAPACITY, AND GRIP STRENGTH?

J Cardiopulm Rehabil Prev 2020 09;40(5):341-344

Cardiopulmonary Physiotherapy Laboratory (LACAP), Department of Physical Therapy, Federal University of São Carlos, Sao Carlos, SP, Brazil (Mr Heubel, Drs Borghi-Silva and Mendes, and Mss Kabbach, Agnoleto, Camargo, and dos Santos); and Department of Medicine, Federal University of São Carlos, Sao Carlos, SP, Brazil (Dr Roscani).

Purpose: Chronic obstructive pulmonary disease (COPD) and abnormalities of left ventricular (LV) geometry often coexist. This study aimed to verify whether LV geometry is associated with airflow obstruction, functional capacity, and grip strength in COPD patients.

Methods: Thirty-seven COPD patients (GOLD II, III, and IV) were allocated to three groups according to LV geometry as assessed by transthoracic echocardiography: normal (n = 13), concentric LV remodeling (n = 8), and concentric LV hypertrophy (LVH) (n = 16). Lung function was assessed using spirometry. The Duke Activity Status Index (DASI) was used to estimate functional capacity, and grip strength measurement was performed using a hydraulic hand dynamometer.

Results: The concentric LVH group presented lower DASI scores (P = .045) and grip strength (P = .006) when compared with the normal group. Correlations analysis showed the following: relative wall thickness negatively correlated with forced expiratory volume in the first second (r = -0.380; P = .025) and DASI score (r = -0.387, P = .018); LV mass index negatively correlated with grip strength (r = -0.363, P = .038).

Conclusions: In COPD patients, LV geometry is associated with airflow limitation, functional capacity, and grip strength. Specifically, concentric LV remodeling is associated with increased airflow limitation and decreased functional capacity whereas increased LV mass is associated with decreased grip strength.
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http://dx.doi.org/10.1097/HCR.0000000000000483DOI Listing
September 2020

Effect of high-intensity exercise on cerebral, respiratory and peripheral muscle oxygenation of HF and COPD-HF patients.

Heart Lung 2021 Jan - Feb;50(1):113-120. Epub 2020 Jul 21.

Cardiopulmonary Physiotherapy Laboratory, Physiotherapy Department, Federal University of Sao Carlos, UFSCar, Rodovia Washington Luis, KM 235, Monjolinho, CEP: 13565-905, Sao Carlos, SP, Brazil. Electronic address:

Objective: To investigate cerebral oxygenation (Cox) responses as well as respiratory (Res) and active peripheral muscle (Pm) O delivery during high-intensity cycling exercise and contrast responses between patients with coexistent chronic obstructive pulmonary disease (COPD)-heart failure (HF) and HF alone.

Methods: Cross-sectional study involving 11 COPD-HF and 11 HF patients. On two different days, patients performed maximal incremental cardiopulmonary exercise testing (CPET) and constant load exercise on a cycle ergometer until the limit of tolerance (Tlim). The high-intensity exercise session was 80% of the peak CPET work rate. Relative blood concentrations of oxyhemoglobin ([OHb]), deoxyhemoglobin ([HHb]) of Res, Pm (right vastus lateralis) and Cox (pre-frontal) were measured using near infrared spectroscopy.

Results: We observed a greater decrease in [OHb] at a lower Tlim in COPD-HF when compared to HF (P < 0.05). [HHb] of Res was higher (P < 0.05) and Tlim was lower in COPD-HF vs. HF. Pm and Cox were lower and Tlim was higher in (P < 0.05) HF vs. COPD-HF. In HF, there was a lower ∆[OHb] and higher ∆ [HHb] of Pm when contrasted to Cox observed during exercise, as well as a lower ∆ [OHb] and higher ∆ [HHb] of Res when contrasted with Cox (P < 0.05). However, COPD-HF patients presented with a higher ∆ [HHb] of Res and Pm when contrasted with Cox (P < 0.05).

Conclusion: The coexistence of COPD in patients with HF produces negative effects on Cox, greater deoxygenation of the respiratory and peripheral muscles and higher exertional dyspnea, which may help to explain an even lower exercise tolerance in this multimorbidity phenotype.
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http://dx.doi.org/10.1016/j.hrtlng.2020.06.013DOI Listing
April 2021

Publisher Correction: The Value of Cardiopulmonary Exercise Testing in Determining Severity in Patients with both Systolic Heart Failure and COPD.

Sci Rep 2020 May 4;10(1):7398. Epub 2020 May 4.

Cardiopulmonary Physiotherapy Laboratory, Physiotherapy Department, Federal University of Sao Carlos, UFSCar, Rod Washington Luis, KM 235, Monjolinho, CEP: 13565-905, Sao Carlos, SP, Brazil.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-64446-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198566PMC
May 2020

The Value of Cardiopulmonary Exercise Testing in Determining Severity in Patients with both Systolic Heart Failure and COPD.

Sci Rep 2020 03 9;10(1):4309. Epub 2020 Mar 9.

Cardiopulmonary Physiotherapy Laboratory, Physiotherapy Department, Federal University of Sao Carlos, UFSCar, Rod Washington Luis, KM 235, Monjolinho, CEP: 13565-905, Sao Carlos, SP, Brazil.

Our aim was to identify optimal cardiopulmonary exercise testing (CPET) threshold values that distinguish disease severity progression in patients with co-existing systolic heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to evaluate the impact of the cut-off determined on the prognosis of hospitalizations. We evaluated 40 patients (30 men and 10 woman) with HF and COPD through pulmonary function testing, doppler echocardiography and maximal incremental CPET on a cycle ergometer. Several significant CPET threshold values were identified in detecting a forced expiratory volume in 1 second (FEV) < 1.6 L: 1) oxygen uptake efficiency slope (OUES) < 1.3; and 2) circulatory power (CP) < 2383 mmHg.mlO.kg. CPET significant threshold values in identifying a left ventricular ejection fraction (LVEF) < 39% were: 1) OUES: < 1.3; 2) CP < 2116 mmHg.mlO.kg.min and minute ventilation/carbon dioxide production (V̇/V̇CO) slope>38. The 15 (38%) patients hospitalized during follow-up (8 ± 2 months). In the hospitalizations analysis, LVEF < 39% and FEV < 1.6, OUES < 1.3, CP < 2116 mmHg.mlO.kg.min and V̇/V̇CO > 38 were a strong risk predictor for hospitalization (P ≤ 0.050). The CPET response effectively identified worsening disease severity in patients with a HF-COPD phenotype. LVEF, FEV CP, OUES, and the V̇/V̇CO slope may be particularly useful in the clinical assessment and strong risk predictor for hospitalization.
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http://dx.doi.org/10.1038/s41598-020-61199-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062717PMC
March 2020

Impact of a Supervised Twelve-Week Combined Physical Training Program in Heart Failure Patients: A Randomized Trial.

Cardiol Res Pract 2019 3;2019:1718281. Epub 2019 Sep 3.

Medical Department, São Carlos Federal University (UFSCar), São Carlos, São Paulo State, Brazil.

Purpose: The aim of this study was to compare the effects of supervised combined physical training and unsupervised physician-prescribed regular exercise on the functional capacity and quality of life of heart failure patients.

Methods: This is a longitudinal prospective study composed of 28 consecutive heart failure with reduced ejection fraction patients randomly divided into two age- and gender-matched groups: trained group ( = 17) and nontrained group ( = 11). All patients were submitted to clinical evaluation, transthoracic echocardiography, the Cooper walk test, and a Quality of Life questionnaire before and after a 12-week study protocol. Categorical variables were expressed as proportions and compared with the chi-square test. Two-way ANOVA was performed to compare the continuous variables considering the cofactor groups and time of intervention, and Pearson correlation tests were conducted for the associations in the same group.

Results: No significant differences between groups were found at baseline. At the end of the protocol, there were improvements in the functional capacity and ejection fraction of the trained group in relation to the nontrained group ( < 0.05). There was time and group interaction for improvement in the quality of life in the trained group.

Conclusions: In patients with heart failure with reduced ejection fraction, supervised combined physical training improved exercise tolerance and quality of life compared with the unsupervised regular exercise prescribed in routine medical consultations. Left ventricular systolic function was improved with supervised physical training.
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http://dx.doi.org/10.1155/2019/1718281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766120PMC
September 2019

Age is the main factor related to expiratory flow limitation during constant load exercise.

Clinics (Sao Paulo) 2018 10 29;73:e439. Epub 2018 Oct 29.

Laboratorio de Fisioterapia Cardiovascular, Nucleo de Pesquisas em Exercicio Fisico, Departamento de Fisioterapia, Universidade Federal de Sao Carlos, Sao Carlos, SP, BR.

Objective: The objective of this study was to investigate the interaction among the determinants of expiratory flow limitation (EFL), peak oxygen uptake (VO2peak), dysanapsis ratio (DR) and age during cycling at different intensities in young and middle-aged men.

Methods: Twenty-two (11 young and 11 middle-aged) men were assessed. Pulmonary function tests (DR), cardiopulmonary exercise tests (VO2peak) and two constant load tests (CLTs) at 75% (moderate intensity) and 125% (high intensity) of the gas exchange threshold were performed to assess EFL. EFL was classified using the percentage of EFL determined from both CLTs (mild: 5%-30%, moderate: 30%-50%, severe: >50%).

Results: Only the middle-aged group displayed EFL at both exercise intensities (p<0.05). However, the number of participants with EFL and the percentage of EFL were only associated with age during high-intensity exercise.

Conclusions: There was no interaction between the determinants. However, age was the only factor that was related to the presence of EFL during exercise in the age groups studied.
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http://dx.doi.org/10.6061/clinics/2018/e439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201139PMC
October 2018

Chronic obstructive pulmonary disease severity and its association with obstructive sleep apnea syndrome: impact on cardiac autonomic modulation and functional capacity.

Int J Chron Obstruct Pulmon Dis 2018;13:1343-1351. Epub 2018 Apr 26.

Cardiopulmonary Physiotherapy Laboratory, Physiotherapy Department, Federal University of São Carlos, São Carlos, São Paulo, Brazil.

Background: The study was conducted to determine the impact of chronic obstructive pulmonary disease (COPD) in association with obstructive sleep apnea syndrome (OSAS) on cardiac autonomic control and functional capacity.

Subjects And Methods: The study was a cross-sectional prospective controlled clinical study. Heart rate variability indices of 24 COPD (n = 12) and COPD+OSAS (n = 12) patients were evaluated and compared by electrocardiographic recordings acquired during rest, active postural maneuver (APM), respiratory sinus arrhythmia maneuver (RSA-m), and the 6-minute walk test (6MWT).

Results: The COPD group presented higher parasympathetic modulation during APM when compared to the COPD+OSAS group ( = 0.02). The COPD+OSAS group presented higher sympathetic modulation during RSA-m when compared to the COPD group ( = 0.00). The performance during 6MWT was similarly impaired in both groups, despite the greater severity of the COPD group.

Conclusion: Subjects with COPD+OSAS present marked sympathetic modulation, and the presence of OSAS in COPD subjects has a negative impact on functional capacity regardless of the severity of lung disease.
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http://dx.doi.org/10.2147/COPD.S156168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927062PMC
October 2018

Association Between Left Ventricle Diastolic Dysfunction and Unfavorable Prognostic Markers in Patients with Aortic Insufficiency.

J Clin Diagn Res 2017 Jun 1;11(6):OC09-OC11. Epub 2017 Jun 1.

Professor, Department of Internal Medicine, Botucatu Medical School, Botucatu, São Paulo, Brazil.

Introduction: The presence of symptoms, systolic dysfunction and Left Ventricle (LV) dilation are considered unfavourable prognostic markers in Aortic Valve Insufficiency (AVI). The role of diastolic dysfunction, which is considered unfavourable outcome marker in cardiac pathologies, is not well established in AVI.

Aim: To evaluate if the presence of diastolic dysfunction may be associated with unfavourable prognostic markers in AVI patients.

Materials And Methods: A cross-sectional prospective study was performed on 22 patients with moderate or severe AVI. They underwent clinical evaluation and transthoracic echocardiography. Associations between clinical, epidemiological and echocardiographic were evaluated by Student t-test for normally distributed variables or Mann-Whitney test for non-normal distribution. Comparison between proportions was performed by Chi-square test.

Results: There was an association between increased LV filling pressure, assessed by E' and E/E' of Mitral Tissue Doppler, and impaired LV systolic function, respectively: R = 0.563, R2 = 0.281; p = 0.008 and R = 0.639, R2 = 0.378; p = 0.002. The LV indexed mass also was inversely associated with the LV ejection fraction (R = 0.62, R2 = 0.35 and p = 0.003).

Conclusion: There was an association of LV diastolic dysfunction and ventricular hypertrophy with impaired left ventricle systolic function. Increased LV filling pressure and LV indexed mass should be considered in the management of AVI patients.
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http://dx.doi.org/10.7860/JCDR/2017/23463.9974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535408PMC
June 2017

Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats.

Cell Physiol Biochem 2016 25;40(3-4):431-442. Epub 2016 Nov 25.

Faculdade de Medicina de Botucatu, Universidade Estadual Paulista - UNESP, Botucatu/SP (Brazil).

Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity.

Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed.

Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia.

Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.
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http://dx.doi.org/10.1159/000452558DOI Listing
February 2017

Strain Pattern on Electrocardiogram Is Associated with Increased Carotid Intima-Media Thickness in Patients with Aortic Valve Stenosis.

Ann Vasc Surg 2016 Aug 27;35:197-202. Epub 2016 May 27.

Internal Medicine Department, Cardiology Division, Botucatu Medical School, Universidade Estadual Paulista - UNESP, São Paulo, Brazil.

Background: Coronary artery disease is present in at least 30% of patients with degenerative aortic stenosis (AS). Atherosclerosis also performs an important role in the progression of AS, because of the similarities of pathological mechanisms in both conditions. The electrocardiogram (EKG) strain pattern is associated with structural myocardial change and subendocardial ischemia and has been worldwide used as a marker of AS severity. We hypothesized that EKG strain pattern would be a marker of atherosclerosis as well in AS patients. The aim of this study was to associate the presence of EKG strain pattern in AS patients with the carotid intima-media thickness (CIMT).

Methods: Fifty-two consecutive patients referred from the cardiology clinic with moderate or severe AS were included in the study and underwent clinical evaluation, EKG, transthoracic echocardiography, and carotid ultrasonography, following statistical analysis of the results.

Results: There was a significant association between left ventricular EKG strain and increased CIMT (P = 0.001). The presence of strain increased the odds of abnormal CIMT (P = 0.004, odds ratio 9.7, 95% confidence interval 2.4-45.0), in a model adjusted for age and clinical diagnosis of systemic arterial hypertension. Additionally, EKG strain was associated with the presence of atherosclerotic plaque in at least one carotid artery (P = 0.011).

Conclusion: Our results suggest that AS patients with EKG strain pattern should be further investigated for the diagnosis of subclinical atherosclerotic disease.
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http://dx.doi.org/10.1016/j.avsg.2016.01.047DOI Listing
August 2016

Antidepressant treatment decreases daily salt intake and prevents heart dysfunction following subchronic aortic regurgitation in rats.

Physiol Behav 2015 May 5;144:124-8. Epub 2015 Mar 5.

Department of Internal Medicine, Botucatu Medical School, UNESP, Brazil.

Depression is a predictor of poor prognosis in patients with heart failure. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) may improve these outcomes. Left ventricular volume overload induced hypertrophy that is associated with aortic regurgitation (AR) leads to ventricular dysfunction and heart failure. The aim of this study was to verify the effects of the SSRI paroxetine on cardiac function, as well as on fluid intake and excretion, in subchronic AR. Male Wistar rats (260 to 280g) received sham (SH) surgery or AR induced by retrograde puncture of the aortic valve leaflets. The presence of AR was confirmed by echocardiography (ECHO) exams. Four weeks after AR surgery, subcutaneous injections of paroxetine (PAR: 10mg/kg 3 times in a week) or saline were administered. The rats were randomly divided into the following 4 groups and treated for 4 weeks: AR-PAR, ARsaline, SH-PAR and SH-saline. At the end of the treatment period, fractional shortening was preserved in AR-PAR, compared to AR-saline (46.6±2.7% vs 38.3±2.2%, respectively). Daily 0.3 M NaCl intake was reduced in PAR-treated rats. Natriuresis was increased in weeks 2-3 after PAR treatment. Our results suggest that augmentation of central 5-HT neurotransmission has a beneficial effect on cardiovascular remodeling following volume overload. The mechanisms underlying this effect are unknown.
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http://dx.doi.org/10.1016/j.physbeh.2015.02.037DOI Listing
May 2015

Invasive tests in pregnancy.

Clinics (Sao Paulo) 2014 Jul;69(7):504

Internal Medicine, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP, Brazil.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081885PMC
http://dx.doi.org/10.6061/clinics/2014(07)12DOI Listing
July 2014

Vitamin D induces increased systolic arterial pressure via vascular reactivity and mechanical properties.

PLoS One 2014 12;9(6):e98895. Epub 2014 Jun 12.

Department of Internal Medicine, Botucatu Medical School, UNESP - Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.

Background/aims: The aim of this study was to evaluate whether supplementation of high doses of cholecalciferol for two months in normotensive rats results in increased systolic arterial pressure and which are the mechanisms involved. Specifically, this study assesses the potential effect on cardiac output as well as the changes in aortic structure and functional properties.

Methods: Male Wistar rats were divided into three groups: 1) Control group (C, n = 20), with no supplementation of vitamin D, 2) VD3 (n = 19), supplemented with 3,000 IU vitamin D/kg of chow; 3) VD10 (n = 21), supplemented with 10,000 IU vitamin D/kg of chow. After two months, echocardiographic analyses, measurements of systolic arterial pressure (SAP), vascular reactivity, reactive oxygen species (ROS) generation, mechanical properties, histological analysis and metalloproteinase-2 and -9 activity were performed.

Results: SAP was higher in VD3 and VD10 than in C rats (p = 0.001). Echocardiographic variables were not different among groups. Responses to phenylephrine in endothelium-denuded aortas was higher in VD3 compared to the C group (p = 0.041). Vascular relaxation induced by acetylcholine (p = 0.023) and sodium nitroprusside (p = 0.005) was impaired in both supplemented groups compared to the C group and apocynin treatment reversed impaired vasodilation. Collagen volume fraction (<0.001) and MMP-2 activity (p = 0.025) was higher in VD10 group compared to the VD3 group. Elastin volume fraction was lower in VD10 than in C and yield point was lower in VD3 than in C.

Conclusion: Our findings support the view that vitamin D supplementation increases arterial pressure in normotensive rats and this is associated with structural and functional vascular changes, modulated by NADPH oxidase, nitric oxide, and extracellular matrix components.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098895PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055656PMC
October 2015

Diastolic function and functional capacity after a single session of continuous positive airway pressure in patients with compensated heart failure.

Clinics (Sao Paulo) 2014 ;69(5):354-9

Departamento de Clínica Médica, Faculdade de Medicina de Botucatu (UNESP), Botucatu, SP, Brazil.

Objective: The effects of acute continuous positive airway pressure therapy on left ventricular diastolic function and functional capacity in patients with compensated systolic heart failure remain unclear.

Methods: This randomized, double-blind, placebo-controlled clinical trial included 43 patients with heart failure and a left ventricular ejection fraction <0.50 who were in functional classes I-III according to the New York Heart Association criteria. Twenty-three patients were assigned to continuous positive airway pressure therapy (10 cmH2O), while 20 patients received placebo with null pressure for 30 minutes. All patients underwent a 6-minute walk test (6MWT) and Doppler echocardiography before and immediately after intervention. Clinicaltrials.gov: NCT01088854.

Results: The groups had similar clinical and echocardiographic baseline variables. Variation in the diastolic function index (e') after intervention was associated with differences in the distance walked in both groups. However, in the continuous positive airway pressure group, this difference was greater (continuous positive airway pressure group: Δ6MWT = 9.44+16.05×Δe', p = 0.002; sham group: Δ6MWT = 7.49+5.38×Δe'; p = 0.015). There was a statistically significant interaction between e' index variation and continuous positive airway pressure for the improvement of functional capacity (p = 0.020).

Conclusions: Continuous positive airway pressure does not acurately change the echocardiographic indexes of left ventricle systolic or diastolic function in patients with compensated systolic heart failure. However, 30-minute continuous positive airway pressure therapy appears to have an effect on left ventricular diastolic function by increasing functional capacity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012238PMC
http://dx.doi.org/10.6061/clinics/2014(05)010DOI Listing
December 2014

Left ventricular sphericity index predicts systolic dysfunction in rats with experimental aortic regurgitation.

J Appl Physiol (1985) 2014 May 3;116(10):1259-62. Epub 2014 Apr 3.

Department of Internal Medicine, Botucatu Medical School, University of Estadual Paulista (Universidade Estadual Paulista "Júlio de Mesquita Filho"), São Paulo, Brazil.

Although an increased left ventricular (LV) diastolic diameter (DD) and a decreased ejection fraction have been used as markers for the surgical replacement of an insufficient aortic valve, these signals may be observed when irreversible myocardium damage has already occurred. The aim of this study was to determine whether change in LV geometry predicts systolic dysfunction in experimental aortic regurgitation. Male Wistar rats underwent surgical acute aorta regurgitation (aorta regurgitation group; n = 23) or a sham operation (sham group; n = 12). After the procedure, serial transthoracic echocardiograms were performed at 1, 4, 8, and 16 wk. At the end of protocol, the LV, lungs, and liver were dissected and weighed. During the follow-up, no animal developed overt heart failure. There was a correlation between the LV sphericity index and reduced fractional shortening (P < 0.001) over time. A multiple regression model showed that the LVDD-sphericity index association at 8 wk was a better predictor of decreased fractional shortening at week 16 (R(2) = 0.50; P < 0.001) than was the LVDD alone (R(2) = 0.39; P = 0.001). LV geometry associated with increased LVDD improved the prediction of systolic dysfunction in experimental aortic regurgitation.
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http://dx.doi.org/10.1152/japplphysiol.00840.2013DOI Listing
May 2014

Anemia, heart failure and evidence-based clinical management.

Arq Bras Cardiol 2013 Jul;101(1):87-92

Faculdade de Medicina de Botucatu – UNESP, São Paulo, SP – Brazil.

Anemia is a prevalent comorbidity and marker of a poorer prognosis in patients with heart failure (HF). Its clinical relevance, as well as its pathophysiology and the clinical management of these patients are important subjects in the specialized literature. In the present review, we describe the current concepts on the pathophysiology of anemia in HF, its diagnostic criteria, and the recommendations for iron supplementation. Also, we make a critical analysis of the major studies showing evidences on the benefits of this supplementation. The four main components of anemia are addressed: chronic disease, dilutional, "renal" and malabsorption. In patients with HF, the diagnostic criteria are the same as those used in the general population: serum ferritin levels lower than 30 mcg/L in patients without kidney diseases and lower than 100 mcg/L or serum ferritin levels between 100-299 mcg/L with transferring saturation lower than 20% in patients with chronic kidney diseases. Finally, the therapeutic possibilities for anemia in this specific patient population are discussed.
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http://dx.doi.org/10.5935/abc.20130126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998166PMC
July 2013

Impact of the length of vitamin D deficiency on cardiac remodeling.

Circ Heart Fail 2013 Jul 24;6(4):809-16. Epub 2013 May 24.

Internal Medicine Department, Botucatu Medical School, UNESP, São Paulo State University, Botucatu, Brazil.

Background: This study was aimed to evaluate the influence of vitamin D (VD) deficiency on cardiac metabolism, morphology, and function. Thus, we investigated the relationship of these changes with the length of the nutrient restriction.

Methods And Results: Male weanling Wistar rats were allocated into 4 groups: C2 (n=24), animals were fed an AIN-93G diet with 1000 IU VD/kg of chow and were kept under fluorescent light for 2 months; D2 (n=22), animals were fed a VD-deficient AIN-93G diet and were kept under incandescent light for 2 months; C4 (n=21) animals were kept in the same conditions of C2 for 4 months; and D4 (n=23) animals were kept in the same conditions of D2 for 4 months. Biochemical analyses showed lower β-hydroxyacyl coenzyme-A dehydrogenase activity and higher lactate dehydrogenase activity in VD-deficient animals. Furthermore, VD deficiency was related to increased cytokines release, oxidative stress, apoptosis, and fibrosis. Echocardiographic data showed left ventricular hypertrophy and lower fractional shortening and ejection fraction in VD-deficient animals. Difference became evident in the lactate dehydrogenase activity, left ventricular weight, right ventricle weight, and left ventricular mass after 4 months of VD deficiency.

Conclusions: Our data indicate that VD deficiency is associated with energetic metabolic changes, cardiac inflammation, oxidative stress, fibrosis and apoptosis, cardiac hypertrophy, left chambers alterations, and systolic dysfunction. Furthermore, length of the restriction influenced these cardiac changes.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.112.000298DOI Listing
July 2013

Impact of hypertension on ventricular remodeling in patients with aortic stenosis.

Arq Bras Cardiol 2011 Sep 29;97(3):254-9. Epub 2011 Jul 29.

Hospital das Clínicas, Faculdade de Medicina de Botucatu-Unesp, Botucatu, SP, Brasil.

Background: Left ventricular hypertrophy (LVH) is a marker of increased cardiovascular risk and is frequently associated with both arterial hypertension (AH) and aortic stenosis (AoS). Also, these two maladies may co-exit in a same patient. However, in these cases, it is not clear the impact of each one in LVH.

Objective: To evaluate LVH and ventricular geometry in patients with AS associated or not with arterial hypertension.

Methods: This was a retrospective, observational and transversal study, including 298 consecutive patients with echocardiographic diagnosis of AoS. LVH was defined as myocardial mass > 224 g for men and > 162 g for women. Patients were classified as having mild (peak gradient < 30 mmHg), moderate (between 30 and 50 mmHg) or severe (> 50 mmHg) AoS and separated into two subgroups: with and without hypertension.

Results: AH was associated with increased ventricular mass in all three levels of aortic stenosis (mild AS: 172 ± 45 g vs 223 ± 73 g, p < 0.0001 moderate AoS: 189 ± 77 g vs 245 ± 81 g, p = 0.0313 severe AoS: 200 ± 62 g vs 252 ± 88 g, p = 0.0372), and increased risk of LVH (OR = 2.1 CI95%:1.2-3.6 p = 0.012). Regarding to geometric remodeling, hypertensive patients with severe AS presented a significant increase in frequency of concentric hypertrophy, when compared with those without hypertension (p = 0.013).

Conclusion: Hypertension is an additional factor of increased left ventricular mass in patients with AS. Also, hypertension was influential in ventricular geometry.
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http://dx.doi.org/10.1590/s0066-782x2011005000081DOI Listing
September 2011

Quality of life in patients with severe and stable coronary atherosclerotic disease.

Arq Bras Cardiol 2010 Dec;95(6):691-7

Hospital Santa Marcelina, São Paulo, SP, Brasil.

Background: There are few data on the factors decreasing quality of life (QoL) in patients with coronary artery disease (CAD) before a percutaneous coronary intervention (PCI).

Objective: To associate clinical variables with QoL scores in patients with stable CAD before the PCI and with unfavorable outcomes, 12 months after the procedure.

Methods: The present is a longitudinal study of 78 patients (43 men and 35 women), before an elective PCI. The associations between the QoL scores (SF-36 questionnaire) and age, sex, weight, body mass index, diabetes mellitus (DM), arterial hypertension, dyslipidemia, current smoking, previous cardiovascular event or PCI, glycemia control and blood pressure (BP) were analyzed by multivariate logistic regression. We also analyzed the associations between the clinical features and the unfavorable outcomes (death due to any cause, heart failure or nonfatal infarction). The level of significance was set at p < 0.05.

Results: The medians of the QoL scores were < 70 percentage in all domains. Female sex, age < 60 years, previous cardiovascular event or PCI, BMI ≥ 25 kg/m², DM and high BP were associated with a higher degree of impairment of at least one QoL score. Female sex (OR: 7.19; 95%CI: 1.55 - 33.36; p = 0.012), previous cardiovascular event (OR: 3.97; 95%CI: 1.01 - 15.66; p = 0.049) and PCI failure (OR: 10.60; 95%CI: 1.83 - 61.46; p = 0.008) were associated with increased risk of combined outcome.

Conclusion: In the presence of CAD, women and patients with comorbidities present a higher degree of QoL impairment. The unfavorable outcomes 12 months after the PCI are associated with the female sex, previous event or procedure failure.
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http://dx.doi.org/10.1590/s0066-782x2010005000151DOI Listing
December 2010

Heart failure with normal ejection fraction.

Arq Bras Cardiol 2010 May;94(5):652-60, 694-702

Faculdade de Medicina de Botucatu, UNESP, São Paulo, Brasil.

Heart failure with normal ejection fraction (HFNEF) is a complex syndrome that has been broadly studied since the last decade. It is caused by diastolic ventricular dysfunction demonstrated by complementary methods, such as hemodynamic study or echocardiogram, in the presence of a normal ejection fraction (EF). It affects primarily elderly individuals with comorbidities, such as systemic arterial hypertension, coronary failure and obesity. The physiopathological mechanisms are complex and multifactorial, involving the myocardial passive stiffness, the ventricular geometry, the pericardial restraint and the interaction between the ventricles. The main objectives of the treatment were to decrease the pulmonary venous congestion and the heart rate and control the comorbidities. There is no strong evidence that the use of specific medications, such as the angiotensin-converting enzyme inhibitors or beta-blockers can influence mortality. The poorer prognostic factors include advanced age, presence of kidney dysfunction, diabetes, functional class III and IV (NYHA) and advanced-stage diastolic dysfunction, with a restrictive pattern of ventricular filling. Another aspect that has been increasingly cited in the literature is the analysis of the role of the systolic function in HFNEF cases. All these aspects are analyzed in detail in the present review.
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http://dx.doi.org/10.1590/s0066-782x2010000500019DOI Listing
May 2010