Publications by authors named "Dirceu Almeida"

57 Publications

Accuracy of Post-thrombolysis ST-segment Reduction as an Adequate Reperfusion Predictor in the Pharmaco-Invasive Approach.

Arq Bras Cardiol 2021 07;117(1):15-25

Universidade Federal de Sao Paulo, São Paulo, SP - Brasil.

Background: Primary percutaneous coronary intervention is considered the "gold standard" for coronary reperfusion. However, when not available, the drug-invasive strategy is an alternative method and the electrocardiogram (ECG) has been used to identify reperfusion success.

Objectives: Our study aimed to assess ST-Segment changes in post-thrombolysis and their power to predict recanalization and using the angiographic scores TIMI-flow and Myocardial Blush Grade (MBG) as an ideal reperfusion criterion.

Methods: 2,215 patients with ST-Segment Elevation Myocardial Infarction (STEMI) undergoing fibrinolysis [(Tenecteplase)-TNK] and referred to coronary angiography within 24 h post-fibrinolysis or immediately referred to rescue therapy were studied. The ECG was performed pre- and 60 min-post-TNK. The patients were categorized into 2 groups: those with ideal reperfusion (TIMI-3 and MBG-3) and those with inadequate reperfusion (TIMI and MBG <3). The ECG reperfusion criterion was defined by the reduction of the ST-Segment >50%. A p-value <0.05 was considered for the analyses, with bicaudal tests.

Results: The ECG reperfusion criterion showed a positive predictive value of 56%; negative predictive value of 66%; sensitivity of 79%; and specificity of 40%. There was a weak positive correlation between ST-Segment reduction and ideal reperfusion angiographic data (r = 0.21; p <0.001) and low diagnostic accuracy, with an AUC of 0.60 (95%CI: 0.57-0.62).

Conclusion: The ST-Segment reduction was not able to accurately identify patients with adequate angiographic reperfusion. Therefore, even patients with apparently successful reperfusion should be referred to angiography soon, to ensure adequate macro and microvascular coronary flow.
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http://dx.doi.org/10.36660/abc.20200241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294746PMC
July 2021

Proportional Assist Ventilation Improves Leg Muscle Reoxygenation After Exercise in Heart Failure With Reduced Ejection Fraction.

Front Physiol 2021 21;12:685274. Epub 2021 Jun 21.

Pulmonary Function and Clinical Exercise Physiology Unit, Division of Respiratory Diseases, Department of Medicine, Federal University of Sao Paulo (UNIFESP), São Paulo, Brazil.

Background: Respiratory muscle unloading through proportional assist ventilation (PAV) may enhance leg oxygen delivery, thereby speeding off-exercise oxygen uptake ( ) kinetics in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).

Methods: Ten male patients (HFrEF = 26 ± 9%, age 50 ± 13 years, and body mass index 25 ± 3 kg m) underwent two constant work rate tests at 80% peak of maximal cardiopulmonary exercise test to tolerance under PAV and sham ventilation. Post-exercise kinetics of , vastus lateralis deoxyhemoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy, and cardiac output (Q ) by impedance cardiography were assessed.

Results: PAV prolonged exercise tolerance compared with sham (587 ± 390 s vs. 444 ± 296 s, respectively; = 0.01). PAV significantly accelerated recovery ( = 56 ± 22 s vs. 77 ± 42 s; < 0.05), being associated with a faster decline in Δ[deoxy-Hb + Mb] and Q compared with sham ( = 31 ± 19 s vs. 42 ± 22 s and 39 ± 22 s vs. 78 ± 46 s, < 0.05). Faster off-exercise decrease in Q with PAV was related to longer exercise duration ( = -0.76; < 0.05).

Conclusion: PAV accelerates the recovery of central hemodynamics and muscle oxygenation in HFrEF. These beneficial effects might prove useful to improve the tolerance to repeated exercise during cardiac rehabilitation.
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http://dx.doi.org/10.3389/fphys.2021.685274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255967PMC
June 2021

Effects of inspiratory muscle training combined with aerobic exercise training on neurovascular control in chronic heart failure patients.

ESC Heart Fail 2021 Jun 28. Epub 2021 Jun 28.

Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.

Aims: We tested the hypothesis that the effects of combined inspiratory muscle training and aerobic exercise training (IMT + AET) on muscle sympathetic nerve activity (MSNA) and forearm blood flow in patients with heart failure with reduced ejection fraction are more pronounced than the effects of AET alone.

Methods And Results: Patients aged 30-70 years, New York Heart Association Functional Class II-III, and left ventricular ejection fraction ≤40% were randomly assigned to four groups: IMT (n = 11), AET (n = 12), IMT + AET (n = 9), and non-training (NT; n = 10). MSNA was recorded using microneurography. Forearm blood flow was measured by venous occlusion plethysmography and inspiratory muscle strength by maximal inspiratory pressure. IMT consisted of 30 min sessions, five times a week, for 4 months. Moderate AET consisted of 60 min sessions, three times a week for 4 months. AET (-10 ± 2 bursts/min, P = 0.03) and IMT + AET (-13 ± 4 bursts/min, P = 0.007) reduced MSNA. These responses in MSNA were not different between AET and IMT + AET groups. IMT (0.22 ± 0.08 mL/min/100 mL, P = 0.03), AET (0.27 ± 0.09 mL/min/100 mL, P = 0.01), and IMT + AET (0.35 ± 0.12 mL/min/100 mL, P = 0.008) increased forearm blood flow. No differences were found between groups. AET (3 ± 1 mL/kg/min, P = 0.006) and IMT + AET (4 ± 1 mL/kg/min, P = 0.001) increased peak oxygen consumption. These responses were similar between these groups. IMT (20 ± 3 cmH O, P = 0.005) and IMT + AET (18 ± 3 cmH O, P = 0.01) increased maximal inspiratory pressure. No significant changes were observed in the NT group.

Conclusions: IMT + AET causes no additive effects on neurovascular control in patients with heart failure with reduced ejection fraction compared with AET alone. These findings may be, in part, because few patients had inspiratory muscle weakness.
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http://dx.doi.org/10.1002/ehf2.13478DOI Listing
June 2021

In patients with heart failure, enhanced ventilatory response to exercise is associated with severe obstructive sleep apnea.

J Clin Sleep Med 2021 May 5. Epub 2021 May 5.

Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.

Study Objectives: Patients with chronic heart failure (CHF) while undergoing exercise test, frequently exhibit elevated ratio of minute ventilation over CO₂ output (VE/VCO₂ slope). One of the factors contributing to this elevated slope is increased chemosensitivity to CO₂, as this slope significantly correlates with the slope of the ventilatory response to CO₂ rebreathing at rest. A previous study in patients with CHF and central sleep apnea (CSA) has shown the highest VE/VCO2 slope during exercise was associated with the most severe CSA. In the current study, we tested the hypothesis that in patients with CHF and obstructive sleep apnea (OSA), the highest VE/VCO₂ slope is also associated with most severe OSA. If correct, it implies that in CHF, augmented instability in the negative feedback system controlling breathing predisposes to both OSA and CSA.

Methods: This preliminary study involved 70 patients with stable CHF and spectrum of OSA severity who underwent full night polysomnography, echocardiography, and cardiopulmonary exercise testing. Peak oxygen consumption (VO₂ max) and VE/VCO₂ slope were calculated.

Results: There were significant positive correlations between apnea hypopnea index (AHI) and VE/VCO₂ slope (r= 0.359; p=0.002). In the regression model, involving relevant variable, age, body mass index, gender, VE/VCO₂ slope, VO₂, and left ventricular ejection fraction, AHI retained significance with VE/VCO₂.

Conclusions: In patients with CHF, the VE/VCO₂ slope obtained during exercise correlates significantly to the severity of OSA suggesting that an elevated CO₂ response should increase suspicion for presence of severe OSA, a treatable disorder that is potentially associated with excess mortality.

Clinical Trial Registration: Registry: ClinicalTrials.gov; Title: Comparison Between Exercise Training and CPAP Treatment for Patients With Heart Failure and Sleep Apnea; Identifier: NCT01538069; URL: https://clinicaltrials.gov/ct2/show/record/NCT01538069.
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http://dx.doi.org/10.5664/jcsm.9396DOI Listing
May 2021

Acute Hemodynamic Index Predicts In-Hospital Mortality in Acute Decompensated Heart Failure.

Arq Bras Cardiol 2021 01;116(1):77-86

Pontifícia Universidade Católica do Paraná, Curitiba, PR - Brasil.

Background: The physical examination enables prognostic evaluation of patients with decompensated heart failure (HF), but lacks reliability and relies on the professional's clinical experience. Considering hemodynamic responses to "fight or flight" situations, such as the moment of admission to the emergency room, we proposed the calculation of the acute hemodynamic index (AHI) from values of heart rate and pulse pressure.

Objective: To evaluate the in-hospital prognostic ability of AHI in decompensated HF.

Methods: A prospective, multicenter, registry-based observational study including data from the BREATHE registry, with information from public and private hospitals in Brazil. The prognostic ability of the AHI was tested by receiver-operating characteristic (ROC) analyses, C-statistics, Akaike's information criteria, and multivariate regression analyses. p-values < 0.05 were considered statistically significant.

Results: We analyzed data from 463 patients with heart failure with low ejection fraction. In-hospital mortality was 9%. The median AHI value was used as cut-off (4 mmHg⋅bpm). A low AHI (≤ 4 mmHg⋅bpm) was found in 80% of deceased patients. The risk of in-hospital mortality in patients with low AHI was 2.5 times that in patients with AHI > 4 mmHg⋅bpm. AHI independently predicted in-hospital mortality in acute decompensated HF (sensitivity: 0.786; specificity: 0.429; AUC: 0.607 [0.540-0.674]; p = 0.010) even after adjusting for comorbidities and medication use [OR: 0.061 (0.007-0.114); p = 0.025).

Conclusions: The AHI independently predicts in-hospital mortality in acute decompensated HF. This simple bed-side index could be useful in an emergency setting. (Arq Bras Cardiol. 2021; 116(1):77-86).
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http://dx.doi.org/10.36660/abc.20190439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159496PMC
January 2021

Implications for Clinical Practice from a Multicenter Survey of Heart Failure Management Centers.

Clinics (Sao Paulo) 2021 20;76:e1991. Epub 2021 Jan 20.

Instituto de Moléstias Cardiovasculares Rio Preto Ltda.

Objectives: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil.

Methods: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment.

Results: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment.

Conclusion: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.
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http://dx.doi.org/10.6061/clinics/2021/e1991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798368PMC
April 2021

Inspiratory Muscle Weakness is Related to Poor Short-Term Outcomes for Heart Transplantation.

Braz J Cardiovasc Surg 2021 Jun 1;36(3):308-317. Epub 2021 Jun 1.

Department of Human Motion Sciences, Federal University of Sao Paulo, São Paulo, Brazil.

Introduction: In heart transplantation (HT) recipients, several factors are critical to promptly adopting appropriate rehabilitation strategies and may be important to predict outcomes way after surgery. This study aimed to determine preoperative patient-related risk factors that could adversely affect the postoperative clinical course of patients undergoing HT.

Methods: Twenty-one hospitalized patients with heart failure undergoing HT were evaluated according to respiratory muscle strength and functional capacity before HT. Mechanical ventilation (MV) time, reintubation rate, and intensive care unit (ICU) length of stay were recorded, and assessed postoperatively.

Results: Inspiratory muscle strength as absolute and percentpredicted values were strongly correlated with MV time (r=-0.61 and r=-0.70, respectively, at P<0.001). Concerning ICU length of stay, only maximal inspiratory pressure (MIP) absolute and percent-predicted values were significantly associated. The absolute |MIP| was significantly negatively correlated with ICU length of stay (r=-0.58 at P=0.006) and the percent-predicted MIP was also significantly negatively correlated with ICU length of stay (r=-0.68 at P=0.0007). No associations were observed between preoperative functional capacity, age, sex, and clinical characteristics and MV time and ICU length of stay in the cohort included in this study. Patients with respiratory muscle weakness had a higher prevalence of prolonged MV, reintubation, and delayed ICU length of stay.

Conclusion: An impairment of preoperative MIP was associated with poorer short-term outcomes following HT. As such, inspiratory muscle strength is an important clinical preoperative marker in patients undergoing HT.
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http://dx.doi.org/10.21470/1678-9741-2020-0344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357387PMC
June 2021

Emerging Topics in Heart Failure: Interventional Heart Failure Therapies.

Arq Bras Cardiol 2020 11;115(5):953-955

Hospital Santa Casa de Misericórdia de Curitiba, Curitiba, PR - Brasil.

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http://dx.doi.org/10.36660/abc.20201086DOI Listing
November 2020

Effects of aerobic and inspiratory training on skeletal muscle microRNA-1 and downstream-associated pathways in patients with heart failure.

J Cachexia Sarcopenia Muscle 2020 02 19;11(1):89-102. Epub 2019 Nov 19.

Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.

Background: The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA-1 expression and downstream-associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients.

Methods: Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II-III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months.

Results: Thirty-three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA-1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = -15 ± 0.03%), and tended to increase the p-AKT /AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = -40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross-sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA-1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO (P = 0.004, rho = 0.51).

Conclusions: AET upregulates microRNA-1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K-AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA-1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross-sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA-1 and in the downstream-associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. ClinicalTrials.gov (Identifier: NCT01747395).
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http://dx.doi.org/10.1002/jcsm.12495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015255PMC
February 2020

Septal Ablation in Obstructive Hypertrophic Cardiomyopathy (oHCM).

Arq Bras Cardiol 2019 04;112(4):439-440

Universidade Federal de São Paulo (UNIFESP), São Paulo, SP - Brazil.

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http://dx.doi.org/10.5935/abc.20190066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459442PMC
April 2019

Effects of Exercise Training and CPAP in Patients With Heart Failure and OSA: A Preliminary Study.

Chest 2018 10 10;154(4):808-817. Epub 2018 Sep 10.

Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.

Background: Exercise and CPAP improve OSA. This study examined the effects of exercise in patients with heart failure (HF) and OSA.

Methods: Patients with HF and OSA were randomized to the following study groups: control, exercise, CPAP, and exercise + CPAP.

Results: Sixty-five participants completed the protocol. Comparing baseline vs 3 months, the mean apnea-hypopnea index (AHI) did not change significantly (in events per hour) in the control group, decreased moderately in the exercise group (28 ± 17 to 18 ± 12; P < .03), and decreased significantly more in the CPAP group (32 ± 25 to 8 ± 11; P < .007) and in the exercise + CPAP group (25 ± 15 to 10 ± 16; P < .007). Peak oxygen consumption, muscle strength, and endurance improved only with exercise. Both exercise and CPAP improved subjective excessive daytime sleepiness, quality of life, and the New York Heart Association functional class. However, compared with the control group, changes in scores on the 36-item Medical Outcomes Study Short Form Survey and Minnesota Living with Heart Failure Questionnaire were only significant in the exercise groups.

Conclusions: In patients with HF and OSA, our preliminary results showed that exercise alone attenuated OSA and improved quality of life more than CPAP. In the landscape treatment of OSA in patients with HF, this analysis is the only randomized trial showing any treatment (in this case, exercise) that improved all the studied parameters. The results highlight the important therapeutic benefits of exercise, particularly because adherence to CPAP is low.
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http://dx.doi.org/10.1016/j.chest.2018.05.011DOI Listing
October 2018

Prognostic value of real-time three-dimensional echocardiography compared to two-dimensional echocardiography in patients with systolic heart failure.

Int J Cardiovasc Imaging 2018 Apr 2;34(4):553-560. Epub 2017 Nov 2.

Cardiology Department, Universidade Federal de São Paulo/Escola Paulista de Medicina (UNIFESP/EPM), Rua Domiciano Leite Ribeiro 51, Apt 13, Bloco 2, Sao Paulo, SP, 04317-000, Brazil.

Heart failure (HF) is associated with morbidity and mortality. Real-time three-dimensional echocardiography (RT3DE) may offer additional prognostic data in patients with HF. The study aimed to evaluate the prognostic value of real-time three-dimensional echocardiography (RT3DE). This is a prospective study that included 89 patients with HF and left ventricular ejection fraction (LVEF) < 0.50 who were followed for 48 months. Left atrium and ventricular volumes and functions were evaluated by RT3DE. TDI and two-dimensional echocardiography parameters were also obtained. The endpoint was a composite of death, heart transplantation and hospitalization for acute decompensated HF. The mean age was 55 ± 11 years, and the LVEF was 0.32 ± 0.10. The composite endpoint occurred in 49 patients (18 deaths, 30 hospitalizations, one heart transplant). Patients with outcomes had greater left atrial volume (40 ± 16 vs. 32 ± 12 mL/m; p < 0.01) and right ventricle diameter (41 ± 9 vs. 37 ± 8 mm, p = 0.01), worse total emptying fraction of the left atrium (36 ± 13% vs. 41 ± 11%; p = 0.03), LVEF (0.30 ± 0.09 vs. 0.34 ± 0.11; p = 0.02), right ventricle fractional area change (34.8 ± 12.1% vs. 39.2 ± 11.3%; p = 0.04), and greater E/e' ratio (19 ± 9 vs. 16 ± 8; p = 0.04) and systolic pulmonary artery pressure (SPAP) (50 ± 15 vs. 36 ± 11 mmHg; p < 0.01). In multivariate analysis, LVEF (OR 4.6; CI 95% 1.2-17.6; p < 0.01) and SPAP (OR 12.5; CI 95% 1.8-86.9; p < 0.01) were independent predictors of patient outcomes. LVEF and the SPAP were independent predictors of outcomes in patients with HF.
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http://dx.doi.org/10.1007/s10554-017-1266-0DOI Listing
April 2018

Neuromuscular electrical stimulation improves exercise tolerance in patients with advanced heart failure on continuous intravenous inotropic support use-randomized controlled trial.

Clin Rehabil 2018 Jan 21;32(1):66-74. Epub 2017 Jun 21.

1 Cardiology and Cardiovascular Surgery Discipline, Sao Paulo Hospital, Federal University of Sao Paulo, São Paulo, Brazil.

Objective: To evaluate the impact of a short-term neuromuscular electrical stimulation program on exercise tolerance in hospitalized patients with advanced heart failure who have suffered an acute decompensation and are under continuous intravenous inotropic support.

Design: A randomized controlled study.

Subjects: Initially, 195 patients hospitalized for decompensated heart failure were recruited, but 70 were randomized.

Intervention: Patients were randomized into two groups: control group subject to the usual care ( n = 35); neuromuscular electrical stimulation group ( n = 35) received daily training sessions to both lower extremities for around two weeks.

Main Measures: The baseline 6-minute walk test to determine functional capacity was performed 24 hours after hospital admission, and intravenous inotropic support dose was daily checked in all patients. The outcomes were measured in two weeks or at the discharge if the patients were sent back home earlier than two weeks.

Results: After losses of follow-up, a total of 49 patients were included and considered for final analysis (control group, n = 25 and neuromuscular electrical stimulation group, n = 24). The neuromuscular electrical stimulation group presented with a higher 6-minute walk test distance compared to the control group after the study protocol (293 ± 34.78 m vs. 265.8 ± 48.53 m, P < 0.001, respectively). Neuromuscular electrical stimulation group also demonstrated a significantly higher dose reduction of dobutamine compared to control group after the study protocol (2.72 ± 1.72 µg/kg/min vs. 3.86 ± 1.61 µg/kg/min, P = 0.001, respectively).

Conclusion: A short-term inpatient neuromuscular electrical stimulation rehabilitation protocol improved exercise tolerance and reduced intravenous inotropic support necessity in patients with advanced heart failure suffering a decompensation episode.
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http://dx.doi.org/10.1177/0269215517715762DOI Listing
January 2018

Sleep-Disordered Breathing Exacerbates Muscle Vasoconstriction and Sympathetic Neural Activation in Patients with Systolic Heart Failure.

Circ Heart Fail 2016 11;9(11)

From the Heart Institute (InCor) (D.M.L.L., P.F.T., E.T.-D., P.A.O., C.M., E.A.B., G.L.-F., C.E.N.) and Radiology Institute (InRad) (R.B.P.), University of São Paulo Medical School, Brazil; Division of Cardiology, Department of Medicine, Federal University of São Paulo, Brazil (D.R.A.); and School of Medicine at University of California, Los Angeles (H.R.M.).

Background: Sleep-disordered breathing (SDB) is common in patients with heart failure (HF), and hypoxia and hypercapnia episodes activate chemoreceptors stimulating autonomic reflex responses. We tested the hypothesis that muscle vasoconstriction and muscle sympathetic nerve activity (MSNA) in response to hypoxia and hypercapnia would be more pronounced in patients with HF and SDB than in patients with HF without SDB (NoSBD).

Methods And Results: Ninety consecutive patients with HF, New York Heart Association functional class II-III, and left ventricular ejection fraction ≤40% were screened for the study. Forty-one patients were enrolled: NoSDB (n=13, 46 [39-53] years) and SDB (n=28, 57 [54-61] years). SDB was characterized by apnea-hypopnea index ≥15 events per hour (polysomnography). Peripheral (10% O and 90% N, with CO titrated) and central (7% CO and 93% O) chemoreceptors were stimulated for 3 minutes. Forearm and calf blood flow were evaluated by venous occlusion plethysmography, MSNA by microneurography, and blood pressure by beat-to-beat noninvasive technique. Baseline forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance were similar between groups. MSNA was higher in the SDB group. During hypoxia, the vascular responses (forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance) were significantly lower in the SDB group compared with the NoSDB group (P<0.01 to all comparisons). Similarly, during hypercapnia, the vascular responses (forearm blood flow, forearm vascular conductance, calf blood flow, and calf vascular conductance) were significantly lower in the SDB group compared with the NoSDB group (P<0.001 to all comparisons). MSNA were higher in response to hypoxia (P=0.024) and tended to be higher to hypercapnia (P=0.066) in the SDB group.

Conclusions: Patients with HF and SDB have more severe muscle vasoconstriction during hypoxia and hypercapnia than HF patients without SDB, which seems to be associated with endothelial dysfunction and, in part, increased MSNA response.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.116.003065DOI Listing
November 2016

A Cycle Ergometer Exercise Program Improves Exercise Capacity and Inspiratory Muscle Function in Hospitalized Patients Awaiting Heart Transplantation: a Pilot Study.

Braz J Cardiovasc Surg 2016 Sep-Oct;31(5):389-395

Disciplina de Cirurgia Cardiovascular e Cardiologia da Escola Paulista de Medicina da Universidade de São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil.

Objective: The purpose of this study was to evaluate the effect of a cycle ergometer exercise program on exercise capacity and inspiratory muscle function in hospitalized patients with heart failure awaiting heart transplantation with intravenous inotropic support.

Methods: Patients awaiting heart transplantation were randomized and allocated prospectively into two groups: 1) Control Group (n=11) - conventional protocol; and 2) Intervention Group (n=7) - stationary cycle ergometer exercise training. Functional capacity was measured by the six-minute walk test and inspiratory muscle strength assessed by manovacuometry before and after the exercise protocols.

Results: Both groups demonstrated an increase in six-minute walk test distance after the experimental procedure compared to baseline; however, only the intervention group had a significant increase (P =0.08 and P =0.001 for the control and intervention groups, respectively). Intergroup comparison revealed a greater increase in the intervention group compared to the control (P <0.001). Regarding the inspiratory muscle strength evaluation, the intragroup analysis demonstrated increased strength after the protocols compared to baseline for both groups; statistical significance was only demonstrated for the intervention group, though (P =0.22 and P <0.01, respectively). Intergroup comparison showed a significant increase in the intervention group compared to the control (P <0.01).

Conclusion: Stationary cycle ergometer exercise training shows positive results on exercise capacity and inspiratory muscle strength in patients with heart failure awaiting cardiac transplantation while on intravenous inotropic support.
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http://dx.doi.org/10.5935/1678-9741.20160078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144561PMC
December 2017

Does Exercise Ventilatory Inefficiency Predict Poor Outcome in Heart Failure Patients With COPD?

J Cardiopulm Rehabil Prev 2016 Nov/Dec;36(6):454-459

Divisions of Respirology (Drs Alencar, Arbex, and Neder, Mss Souza and Sperandio, and Messrs Rocha and Hirai) and Cardiology (Drs Mancuso and Almeida), Federal University of Sao Paulo, Brazil; Respiratory Investigation Unit and Laboratory of Clinical Exercise Physiology, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada (Mr Hirai and Drs O'Donnel and Neder); Department of Physiotherapy, Federal University of Sao Carlos, Brazil (Mss Mazzuco and Borghi-Silva); and Division of Respirology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil (Dr Berton).

Purpose: To investigate whether the opposite effects of heart failure (HF) and chronic obstructive pulmonary disease (COPD) on exercise ventilatory inefficiency (minute ventilation [(Equation is included in full-text article.)E]-carbon dioxide output [(Equation is included in full-text article.)CO2] relationship) would negatively impact its prognostic relevance.

Methods: After treatment optimization and an incremental cardiopulmonary exercise test, 30 male patients with HF-COPD (forced expiratory volume in 1 second [FEV1] = 57% ± 17% predicted, ejection fraction = 35% ± 6%) were prospectively followed up during 412 ± 261 days for major cardiac events.

Results: Fourteen patients (46%) had a negative outcome. Patients who had an event had lower echocardiographically determined right ventricular fractional area change (RVFAC), greater ventilatory inefficiency (higher (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir), and lower end-tidal CO2 (PETCO2) (all P < .05). Multivariate Cox models revealed that (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir >36, ΔPETCO2(PEAK-REST)≥2 mm Hg, and PETCO2PEAK≤33 mm Hg added prognostic value to RVFAC≤45%. Kaplan-Meyer analyses showed that although 18% of patients with RVFAC>45% had a major cardiac event after 1 year, no patient with RVFAC>45% and (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir ≤36 (or PETCO2PEAK>33 mm Hg) had a negative event. Conversely, although 69% of patients with RVFAC≤45% had a major cardiac event after 1 year, all patients with RVFAC≤45% and ΔPETCO2(PEAK-REST)≥2 mm Hg had a negative event.

Conclusion: Ventilatory inefficiency remains a powerful prognostic marker in HF despite the presence of mechanical ventilatory constraints induced by COPD. If these preliminary findings are confirmed in larger studies, optimal thresholds for outcome prediction are likely greater than those traditionally recommended for HF patients without COPD.
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http://dx.doi.org/10.1097/HCR.0000000000000212DOI Listing
December 2017

Exercise Ventilation in COPD: Influence of Systolic Heart Failure.

COPD 2016 12 12;13(6):693-699. Epub 2016 May 12.

a Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE), Division of Respirology, Federal University of Sao Paulo , Sao Paulo , Brazil.

Systolic heart failure is a common and disabling co-morbidity of chronic obstructive pulmonary disease (COPD) which may increase exercise ventilation due to heightened neural drive and/or impaired pulmonary gas exchange efficiency. The influence of heart failure on exercise ventilation, however, remains poorly characterized in COPD. In a prospective study, 98 patients with moderate to very severe COPD [41 with coexisting heart failure; 'overlap' (left ventricular ejection fraction < 50%)] underwent an incremental cardiopulmonary exercise test (CPET). Compared to COPD, overlap had lower peak exercise capacity despite higher FEV. Overlap showed lower operating lung volumes, greater ventilatory inefficiency and larger decrements in end-tidal CO (PETCO) (P < 0.05). These results were consistent with those found in FEV-matched patients. Larger areas under receiver operating characteristic curves to discriminate overlap from COPD were found for ventilation ([Formula: see text]E)-CO output [Formula: see text]CO) intercept, [Formula: see text]E-[Formula: see text]CO slope, peak [Formula: see text]E/[Formula: see text]CO ratio and peak PETCO. Multiple logistic regression analysis revealed that [Formula: see text]CO intercept ≤ 3.5 L/minute [odds ratios (95% CI) = 7.69 (2.61-22.65), P < 0.001] plus [Formula: see text]E-[Formula: see text]CO slope ≥ 34 [2.18 (0.73-6.50), P = 0.14] or peak [Formula: see text]E/[Formula: see text]CO ratio ≥ 37 [5.35 (1.96-14.59), P = 0.001] plus peak PETCO ≤ 31 mmHg [5.73 (1.42-23.15), P = 0.01] were indicative of overlapping. Heart failure increases the ventilatory response to metabolic demand in COPD. Variables reflecting excessive ventilation might prove useful to assist clinical interpretation of CPET responses in COPD patients presenting heart failure as co-morbidity.
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http://dx.doi.org/10.1080/15412555.2016.1174985DOI Listing
December 2016

Effects of Zolpidem CR on Sleep and Nocturnal Ventilation in Patients with Heart Failure.

Sleep 2016 Aug 1;39(8):1501-5. Epub 2016 Aug 1.

Department of Psychobiology, Sleep Division, Universidade Federal de Sao Paulo, Brazil.

Study Objective: This study aimed to evaluate the effects of zolpidem CR (controlled release) on sleep and nocturnal ventilation in patients with congestive heart failure, a population at risk for insomnia and poor sleep quality.

Methods: Fifteen patients with heart failure (ischemic cardiomyopathy) and ejection fraction ≤ 45% in NYHA functional class I or II were evaluated with full polysomnography in a placebo-controlled, double-blind, randomized trial. Patients underwent three tests: (1) baseline polysomnography and, after randomization, (2) a new test with zolpidem CR 12.5 mg or placebo, and after 1 week, (3) a new polysomnography, crossing the "medication" used.

Results: A 16% increase in total sleep time was found with the use of zolpidem CR and an increase in stage 3 NREM sleep (slow wave sleep). The apnea hypopnea index (AHI) did not change with zolpidem CR even after controlling for supine position; however, a slight but significant decrease was observed in lowest oxygen saturation compared with baseline and placebo conditions (83.60 ± 5.51; 84.43 ± 3.80; 80.71 ± 5.18, P = 0.002).

Conclusion: Zolpidem CR improved sleep structure in patients with heart failure, did not change apnea hypopnea index, but slightly decreased lowest oxygen saturation.
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http://dx.doi.org/10.5665/sleep.6006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945308PMC
August 2016

Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD.

COPD 2016 08 20;13(4):407-15. Epub 2016 Jan 20.

a Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE), Respiratory Division , Federal University of São Paulo (UNIFESP) , São Paulo , Brazil.

Heart failure, a prevalent and disabling co-morbidity of COPD, may impair cardiac output and muscle blood flow thereby contributing to exercise intolerance. To investigate the role of impaired central and peripheral hemodynamics in limiting exercise tolerance in COPD-heart failure overlap, cycle ergometer exercise tests at 20% and 80% peak work rate were performed by overlap (FEV1 = 56.9 ± 15.9% predicted, ejection fraction = 32.5 ± 6.9%; N = 16), FEV1-matched COPD (N = 16), ejection fraction-matched heart failure patients (N = 15) and controls (N = 12). Differences (Δ) in cardiac output (impedance cardiography) and vastus lateralis blood flow (indocyanine green) and deoxygenation (near-infrared spectroscopy) between work rates were expressed relative to concurrent changes in muscle metabolic demands (ΔO2 uptake). Overlap patients had approximately 30% lower endurance exercise tolerance than COPD and heart failure (p < 0.05). ΔBlood flow was closely proportional to Δcardiac output in all groups (r = 0.89-0.98; p < 0.01). Overlap showed the largest impairments in Δcardiac output/ΔO2 uptake and Δblood flow/ΔO2 uptake (p < 0.05). Systemic arterial oxygenation, however, was preserved in overlap compared to COPD. Blunted limb perfusion was related to greater muscle deoxygenation and lactate concentration in overlap (r = 0.78 and r = 0.73, respectively; p < 0.05). ΔBlood flow/ΔO2 uptake was related to time to exercise intolerance only in overlap and heart failure (p < 0.01). In conclusion, COPD and heart failure add to decrease exercising cardiac output and skeletal muscle perfusion to a greater extent than that expected by heart failure alone. Treatment strategies that increase muscle O2 delivery and/or decrease O2 demand may be particularly helpful to improve exercise tolerance in COPD patients presenting heart failure as co-morbidity.
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http://dx.doi.org/10.3109/15412555.2015.1117435DOI Listing
August 2016

I Brazilian Registry of Heart Failure - Clinical Aspects, Care Quality and Hospitalization Outcomes.

Arq Bras Cardiol 2015 Jun 3;104(6):433-42. Epub 2015 Apr 3.

Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Background: Heart failure (HF) is one of the leading causes of hospitalization in adults in Brazil. However, most of the available data is limited to unicenter registries. The BREATHE registry is the first to include a large sample of hospitalized patients with decompensated HF from different regions in Brazil.

Objective: Describe the clinical characteristics, treatment and prognosis of hospitalized patients admitted with acute HF.

Methods: Observational registry study with longitudinal follow-up. The eligibility criteria included patients older than 18 years with a definitive diagnosis of HF, admitted to public or private hospitals. Assessed outcomes included the causes of decompensation, use of medications, care quality indicators, hemodynamic profile and intrahospital events.

Results: A total of 1,263 patients (64±16 years, 60% women) were included from 51 centers from different regions in Brazil. The most common comorbidities were hypertension (70.8%), dyslipidemia (36.7%) and diabetes (34%). Around 40% of the patients had normal left ventricular systolic function and most were admitted with a wet-warm clinical-hemodynamic profile. Vasodilators and intravenous inotropes were used in less than 15% of the studied cohort. Care quality indicators based on hospital discharge recommendations were reached in less than 65% of the patients. Intrahospital mortality affected 12.6% of all patients included.

Conclusion: The BREATHE study demonstrated the high intrahospital mortality of patients admitted with acute HF in Brazil, in addition to the low rate of prescription of drugs based on evidence.
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http://dx.doi.org/10.5935/abc.20150031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484675PMC
June 2015

Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated Cardiomyopathy.

Arq Bras Cardiol 2015 Jul 8;105(1):65-70. Epub 2015 May 8.

Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BR.

Background: Left atrial volume (LAV) is a predictor of prognosis in patients with heart failure.

Objective: We aimed to evaluate the determinants of LAV in patients with dilated cardiomyopathy (DCM).

Methods: Ninety patients with DCM and left ventricular (LV) ejection fraction ≤ 0.50 were included. LAV was measured with real-time three-dimensional echocardiography (eco3D). The variables evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue Doppler e' wave, E/e' ratio, intraventricular dyssynchrony, 3D dyssynchrony index and mitral regurgitation vena contracta. Pearson's coefficient was used to identify the correlation of the LAV with the assessed variables. A multiple linear regression model was developed that included LAV as the dependent variable and the variables correlated with it as the predictive variables.

Results: Mean age was 52 ± 11 years-old, LV ejection fraction: 31.5 ± 8.0% (16-50%) and LAV: 39.2±15.7 ml/m2. The variables that correlated with the LAV were LV end-diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p < 0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01), E/e' ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A multivariate analysis identified the E/e' ratio (p = 0.02) and mitral regurgitation (p = 0.02) as the only independent variables associated with LAV increase.

Conclusion: The LAV is independently determined by LV filling pressures (E/e' ratio) and mitral regurgitation in DCM.
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http://dx.doi.org/10.5935/abc.20150042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523289PMC
July 2015

Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients.

Am J Physiol Heart Circ Physiol 2015 May 6;308(9):H1096-102. Epub 2015 Mar 6.

Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil,

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg(-1)·min(-1) were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.
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http://dx.doi.org/10.1152/ajpheart.00723.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551124PMC
May 2015

Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure.

Am J Physiol Heart Circ Physiol 2014 Dec 10;307(11):H1655-66. Epub 2014 Oct 10.

Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil; School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil;

Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). The purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients. 2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle. 3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions <40% were randomized to untrained (n = 17; 54 ± 2 yr) or exercise-trained (n = 17; 56 ± 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4, and thromboxane-A2 receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-κB/IκB-α ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle.
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http://dx.doi.org/10.1152/ajpheart.00136.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255006PMC
December 2014

Criteria for mitral regurgitation classification were inadequate for dilated cardiomyopathy.

Arq Bras Cardiol 2013 Nov 8;101(5):457-65. Epub 2013 Oct 8.

Background: Mitral regurgitation (MR) is common in patients with dilated cardiomyopathy (DCM). It is unknown whether the criteria for MR classification are inadequate for patients with DCM.

Objective: We aimed to evaluate the agreement among the four most common echocardiographic methods for MR classification.

Methods: Ninety patients with DCM were included. Functional MR was classified using four echocardiographic methods: color flow jet area (JA), vena contracta (VC), effective regurgitant orifice area (ERO) and regurgitant volume (RV). MR was classified as mild, moderate or important according to the American Society of Echocardiography criteria and by dividing the values into terciles. The Kappa test was used to evaluate whether the methods agreed, and the Pearson correlation coefficient was used to evaluate the correlation between the absolute values of each method.

Results: MR classification according to each method was as follows: JA: 26 mild, 44 moderate, 20 important; VC: 12 mild, 72 moderate, 6 important; ERO: 70 mild, 15 moderate, 5 important; RV: 70 mild, 16 moderate, 4 important. The agreement was poor among methods (kappa=0.11; p<0.001). It was observed a strong correlation between the absolute values of each method, ranging from 0.70 to 0.95 (p<0.01) and the agreement was higher when values were divided into terciles (kappa = 0.44; p < 0.01) CONCLUSION: The use of conventional echocardiographic criteria for MR classification seems inadequate in patients with DCM. It is necessary to establish new cutoff values for MR classification in these patients.
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http://dx.doi.org/10.5935/abc.20130200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081170PMC
November 2013

Heart failure impairs cerebral oxygenation during exercise in patients with COPD.

Eur Respir J 2013 Nov 30;42(5):1423-6. Epub 2013 Jul 30.

Dept of Medicine, Division of Respiratory Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo.

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http://dx.doi.org/10.1183/09031936.00090913DOI Listing
November 2013

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure.

Am J Physiol Heart Circ Physiol 2012 Dec 28;303(12):H1474-80. Epub 2012 Sep 28.

Pulmonary Function and Clinical Exercise Physiology Unit, Division of Respiratory Diseases, Department of Medicine, Federal University of São Paulo, Brazil.

Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O(2)) delivery (Qo(2mv)) to O(2) uptake (Vo(2)) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Qo(2mv)-to-O(2) utilization matching and Vo(2) kinetics, 10 males with CHF (ejection fraction = 27 ± 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath Vo(2), fractional O(2)extraction in the vastus lateralis {∼deoxygenated hemoglobin + myoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ∼20%, an effect that was related to faster on- and off-exercise Vo(2) kinetics (P < 0.05). Active treatment, however, failed to accelerate CO dynamics (P > 0.05). On-exercise [deoxy-Hb + Mb] kinetics were slowed by sildenafil (∼25%), and a subsequent response "overshoot" (n = 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (∼15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise Vo(2) kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0.05). Sildenafil intake enhanced intramuscular Qo(2mv)-to-Vo(2) matching with beneficial effects on Vo(2) kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.
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http://dx.doi.org/10.1152/ajpheart.00435.2012DOI Listing
December 2012
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