RESUMO
BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), impaired augmentation of stroke volume and diastolic dysfunction contribute to exercise intolerance. Systolic-diastolic (S-D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during early diastole. Impaired S-D coupling may contribute to the impaired cardiac response to exercise in patients with HCM. METHODS: Patients with HCM (n = 25, age = 47 ± 9 years) and healthy adults (n = 115, age = 49 ± 10 years) underwent a cardiopulmonary exercise testing (CPET) and echocardiogram. S-D coupling was defined as the ratio of LV longitudinal excursion of the mitral annulus during early diastole (EDexc) and systole (Sexc) and compared between groups. Peak oxygen uptake (peak VÌO2) (Douglas bags), cardiac index (C2H2 rebreathe), and stroke volume index (SVi) were assessed during CPET. Linear regression was performed between S-D coupling and peak VÌO2, peak cardiac index, and peak SVi. RESULTS: S-D coupling was lower in HCM (Controls: 0.63 ± 0.08, HCM: 0.56 ± 0.10, p < 0.001). Peak VÌO2 and stroke volume reserve were lower in patients with HCM (Peak VO2 Controls: 28.5 ± 5.5, HCM: 23.7 ± 7.2 mL/kg/min, p < 0.001, SV reserve: Controls 39 ± 16, HCM 30 ± 18 mL, p = 0.008). In patients with HCM, S-D coupling was associated with peak VÌO2 (r = 0.47, p = 0.018), peak cardiac index (r = 0.60, p = 0.002), and peak SVi (r = 0.63, p < 0.001). CONCLUSION: Systolic-diastolic coupling was impaired in patients with HCM and was associated with fitness and the cardiac response to exercise. Inefficient S-D coupling may link insufficient stroke volume generation, diastolic dysfunction, and exercise intolerance in HCM.
Assuntos
Cardiomiopatia Hipertrófica , Diástole , Teste de Esforço , Volume Sistólico , Sístole , Humanos , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Teste de Esforço/métodos , Volume Sistólico/fisiologia , Ecocardiografia/métodos , Tolerância ao Exercício/fisiologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Adulto , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologiaRESUMO
Compression sonography has been proposed as a method for non-invasive measurement of venous pressures during spaceflight, but initial reports of venous pressure measured by compression ultrasound conflict with prior reports of invasively measured central venous pressure (CVP). The aim of this study is to determine the agreement of compression sonography of the internal jugular vein (IJVP) with invasive measures of CVP over a range of pressures relevant to microgravity exposure. Ten healthy volunteers (18-55 years, five female) completed two 3-day sessions of supine bed rest to simulate microgravity. IJVP and CVP were measured in the seated position, and in the supine position throughout 3 days of bed rest. The range of CVP recorded was in line with previous reports of CVP during changes in posture on Earth and in microgravity. The correlation between IJVP and CVP was poor when measured during spontaneous breathing (r = 0.29; R2 = 0.09; P = 0.0002; standard error of the estimate (SEE) = 3.0 mmHg) or end-expiration CVP (CVPEE ; r = 0.19; R2 = 0.04; P = 0.121; SEE = 3.0 mmHg). There was a modest correlation between the change in CVP and the change in IJVP for both spontaneous ΔCVP (r = 0.49; R2 = 0.24; P < 0.0001) and ΔCVPEE (r = 0.58; R2 = 0.34; P < 0.0001). Bland-Altman analysis of IJVP revealed a large positive bias compared to spontaneous breathing CVP (3.6 mmHg; SD = 4.0; CV = 85%; P < 0.0001) and CVPEE (3.6 mmHg; SD = 4.2; CV = 84%; P < 0.0001). Assessment of absolute IJVP via compression sonography correlated poorly with direct measurements of CVP by invasive catheterization over a range of venous pressures that are physiologically relevant to spaceflight. However, compression sonography showed modest utility for tracking changes in venous pressure over time. NEW FINDINGS: What is the central question of this study? Compression sonography has been proposed as a novel method for non-invasive measurement of venous pressures during spaceflight. However, the accuracy has not yet been confirmed in the range of CVP experienced by astronauts during spaceflight. What is the main finding and its importance? Our data show that compression sonography of the internal jugular vein correlates poorly with direct measurement of central venous pressures in a range that is physiologically relevant to spaceflight. However, compression sonography showed modest utility for tracking changes in venous pressure over time.
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Repouso em Cama , Veias Jugulares , Humanos , Feminino , Veias Jugulares/diagnóstico por imagem , Veias Jugulares/fisiologia , Pressão Venosa , Pressão Venosa Central/fisiologia , UltrassonografiaRESUMO
Background Moderate intensity exercise training (MIT) is safe and effective for patients with hypertrophic cardiomyopathy, yet the efficacy of high intensity training (HIT) remains unknown. This study aimed to compare the efficacy of HIT compared with MIT in patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy were randomized to either 5 months of MIT, or 1 month of MIT followed by 4 months of progressive HIT. Peak oxygen uptake (VËO2; Douglas bags), cardiac output (acetylene rebreathing), and arteriovenous oxygen difference (Fick equation) were measured before and after training. Left ventricular outflow gradient and volumes were measured by echocardiography. Fifteen patients completed training (MIT, n=8, age 52±7 years; HIT, n=7, age 42±8 years). Both HIT and MIT improved peak VËO2 by 1.3 mL/kg per min (P=0.009). HIT (+1.5 mL/kg per min) had a slightly greater effect than MIT (+1.1 mL/kg per min) but with no statistical difference (group×exercise P=0.628). A greater augmentation of arteriovenous oxygen difference occurred with exercise (Δ1.6 mL/100 mL P=0.005). HIT increased left ventricular end-diastolic volume (+17 mL, group×exercise P=0.015) compared with MIT. No serious arrhythmias or adverse cardiac events occurred. Conclusions This randomized trial of exercise training in patients with hypertrophic cardiomyopathy demonstrated that both HIT and MIT improved fitness without clear superiority of either. Although the study was underpowered for safety outcomes, no serious adverse events occurred. Exercise training resulted in salutary peripheral and cardiac adaptations. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03335332.
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Cardiomiopatia Hipertrófica , Sistema Cardiovascular , Humanos , Pessoa de Meia-Idade , Adulto , Exercício Físico , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/terapia , Coração , OxigênioRESUMO
OBJECTIVE: The aim of this retrospective study was to determine whether regional epicardial adipose tissue (EAT) exerts localized effects on adjacent myocardial left ventricular (LV) function. METHODS: Cardiac magnetic resonance imaging (MRI), echocardiography, dual-energy x-ray absorptiometry, and exercise testing were performed in 71 patients with obesity with elevated cardiac biomarkers and visceral fat. Total and regional (anterior, inferior, lateral, right ventricular) EAT was quantified by MRI. Diastolic function was quantified by echocardiography. MRI was used to quantify regional longitudinal LV strain. RESULTS: EAT was associated with visceral adiposity (r = 0.47, p < 0.0001) but not total fat mass. Total EAT was associated with markers of diastolic function (early tissue Doppler relaxation velocity [e'], mitral inflow velocity ratio [E/A], early mitral inflow/e' ratio [E/e']), but only E/A remained significant after adjustment for visceral adiposity (r = -0.30, p = 0.015). Right ventricular and LV EAT had similar associations with diastolic function. There was no evidence for localized effects of regional EAT deposition on adjacent regional longitudinal strain. CONCLUSIONS: There was no association between regional EAT deposition and corresponding regional LV segment function. Furthermore, the association between total EAT and diastolic function was attenuated after adjustment for visceral fat, indicating that systemic metabolic impairments contribute to diastolic dysfunction in high-risk middle-aged adults.
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Pericárdio , Disfunção Ventricular Esquerda , Adulto , Pessoa de Meia-Idade , Humanos , Estudos Retrospectivos , Pericárdio/diagnóstico por imagem , Tecido Adiposo , Função Ventricular Esquerda , Diástole , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/patologiaRESUMO
AIMS: To determine the efficacy of two doses of external counterpulsation (ECP) on glycemic control in people with type 2 diabetes mellitus (T2D), and any persistent benefits 7 weeks following treatment. METHODS: 50 participants with T2D were randomly assigned to either 1) 20x45-minute ECP sessions over 7 weeks (ECP45), 2) 20x30-minute ECP sessions over 7 weeks (ECP30) or 3) SHAM control. Outcomes were assessed at baseline, after 7 weeks of the intervention and 7 weeks after the interventions finished. Efficacy was determined from changes in HbA1c. RESULTS: After 7 weeks, there were significant between-group differences, with ECP45 lowering HbA1c compared to SHAM (mean [95% CI] -0.7 [-0.1 to -1.3] %; -7 [-1 to -15] mmol/mol). Within group changes were; ECP45 (mean ± SD -0.8 ± 0.8%; -8 ± 8 mmol/mol), ECP30 (-0.2 ± 0.5%; -2 ± 6 mmol/mol) and SHAM (-0.1 ± 0.9%; -1 ± 10 mmol/mol). HbA1c in the ECP45 group remained lower 7 weeks after completing the intervention; ECP45 (7.0 ± 1.1%; 53 ± 26 mmol/mol), ECP30 (7.7 ± 1.4%; 60 ± 16 mmol/mol) and SHAM (7.7 ± 1.0%; 60 ± 10 mmol/mol). CONCLUSIONS: In people with T2D, ECP45 for 7 weeks improved glycemic control when compared to ECP30 and a SHAM control group.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Glicemia , Controle Glicêmico , Hemoglobinas Glicadas , Resultado do TratamentoRESUMO
Patients with HFpEF experience severe exercise intolerance due in part to peripheral vascular and skeletal muscle impairments. Interventions targeting peripheral adaptations to exercise training may reverse vascular dysfunction, increase peripheral oxidative capacity, and improve functional capacity in HFpEF. Determine if 8 weeks of isolated knee extension exercise (KE) training will reverse vascular dysfunction, peripheral oxygen utilization, and exercise capacity in patients with HFpEF. Nine HFpEF patients (66 ± 5 years, 6 females) performed graded IKE exercise (5, 10, and 15 W) and maximal exercise testing (cycle ergometer) before and after IKE training (3x/week, 30 min/leg). Femoral blood flow (ultrasound) and leg vascular conductance (LVC; index of vasodilation) were measured during graded IKE exercise. Peak pulmonary oxygen uptake (VÌO2 ; Douglas bags) and cardiac output (QC ; acetylene rebreathe) were measured during graded maximal cycle exercise. IKE training improved LVC (pre: 810 ± 417, post: 1234 ± 347 ml/min/100 mmHg; p = 0.01) during 15 W IKE exercise and increased functional capacity by 13% (peak VÌO2 during cycle ergometry; pre:12.4 ± 5.2, post: 14.0 ± 6.0 ml/min/kg; p = 0.01). The improvement in peak VÌO2 was independent of changes in QÌc (pre:12.7 ± 3.5, post: 13.2 ± 3.9 L/min; p = 0.26) and due primarily to increased a-vO2 difference (pre: 10.3 ± 1.6, post: 11.0 ± 1.7; p = 0.02). IKE training improved vasodilation and functional capacity in patients with HFpEF. Exercise interventions aimed at increasing peripheral oxidative capacity may be effective therapeutic options for HFpEF patients.
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Insuficiência Cardíaca , Vasodilatação , Exercício Físico/fisiologia , Tolerância ao Exercício/fisiologia , Feminino , Humanos , Músculo Esquelético/metabolismo , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologia , Volume Sistólico/fisiologiaRESUMO
Patients with hypertrophic cardiomyopathy (HCM) often have reduced exercise capacity, and it is unclear whether cardiovascular regulation during exercise is intact in these patients. We aimed to determine the relationship between cardiac output (QÌc) and oxygen uptake (VÌo2), and stroke volume (SV) reserve in HCM compared with healthy participants and participants with left ventricular hypertrophy (LVH) but not HCM. Sixteen patients with HCM (48 ± 7 yr, 44% female), 16 participants with LVH (49 ± 5 yr, 44% female), and 61 healthy controls (CON: 52 ± 5 yr, 52% female) completed submaximal steady-state treadmill exercise followed by a maximal exercise test. VÌo2, QÌc, SV, and arteriovenous oxygen difference were measured during rest and exercise, and QÌc/VÌo2 slopes were constructed, The QÌc/VÌo2 slope was blunted in HCM compared with CON and LVH [HCM 4.9 ± 0.7 vs. CON 5.5 ± 1.0 (P = 0.027) vs. LVH 6.0 ± 1.0 AU (P = 0.002)] and participants with HCM had a lower SV reserve (HCM 53 ± 33%, controls 83 ± 33%, LVH 82 ± 22%; HCM vs. controls P = 0.002; HCM vs. LVH P = 0.015). Despite a blunted QÌc/VÌo2 slope, 75% of patients with HCM achieved ≥80% predicted VÌo2max by augmenting a-vo2 difference at maximal exercise (16.0 ± 0.8 mL/100 mL vs. 13.8 ± 2.7 mL/100 mL, P = 0.021). Patients with HCM do not appropriately match QÌc to metabolic demand, primarily due to inadequate stroke volume augmentation. Despite this central limitation, many patients achieve normal exercise capacities by significantly increasing peripheral oxygen extraction.NEW & NOTEWORTHY Through state-of-the-art hemodynamic and oxygen uptake methodologies, this study found the cardiac output response to increasing metabolic demand is blunted among patients with hypertrophic cardiomyopathy (HCM), primarily due to a reduced stroke volume reserve. Many patients with HCM augment their peripheral oxygen extraction during maximal exercise to achieve normal exercise capacity and overcome ineffective matching of cardiac output. Peripheral adaptations that compensate for cardiac limitations may contribute to the heterogeneity of functional limitations observed within this patient population.
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Cardiomiopatia Hipertrófica , Débito Cardíaco , Cardiomiopatia Hipertrófica/metabolismo , Teste de Esforço/métodos , Feminino , Humanos , Hipertrofia Ventricular Esquerda , Masculino , Oxigênio , Volume Sistólico/fisiologiaRESUMO
OBJECTIVES: This study aims to determine whether 1 year of high-intensity interval training (HIIT) and omega-3 fatty acid (n-3 FA) supplementation would improve fitness, cardiovascular structure/function, and body composition in obese middle-aged adults at high-risk of heart failure (HF) (stage A). BACKGROUND: It is unclear if intensive lifestyle interventions begun in stage A HF can improve key cardiovascular and metabolic risk factors. METHODS: High-risk obese adults (n = 80; age 40 to 55 years; N-terminal pro-B-type natriuretic peptide >40 pg/mL or high-sensitivity cardiac troponin T >0.6 pg/mL; visceral fat >2 kg) were randomized to 1 year of HIIT exercise or attention control, with n-3 FA (1.6 g/daily omega-3-acid ethyl esters) or placebo supplementation (olive oil 1.6 g daily). Outcome variables were exercise capacity quantified as peak oxygen uptake (V.O2), left ventricular (LV) mass, LV volume, myocardial triglyceride content (magnetic resonance spectroscopy), arterial stiffness/function (central pulsed-wave velocity; augmentation index), and body composition (dual x-ray absorptiometry scan). RESULTS: Fifty-six volunteers completed the intervention. There was no detectible effect of HIIT on visceral fat or myocardial triglyceride content despite a reduction in total adiposity (Δ: -2.63 kg, 95% CI: -4.08 to -0.46, P = 0.018). HIIT improved exercise capacity by â¼24% (ΔV.O2: 4.46 mL/kg per minute, 95% CI: 3.18 to 5.56; P < 0.0001), increased LV mass (Δ: 9.40 g, 95% CI: 4.36 to 14.44; P < 0.001), and volume (Δ: 12.33 mL, 95 % CI: 5.61 to 19.05; P < 0.001) and reduced augmentation index (Δ: -4.81%, 95% CI: -8.63 to -0.98; P = 0.009). There was no independent or interaction effect of n-3 FA on any outcome. CONCLUSIONS: One-year HIIT improved exercise capacity, cardiovascular structure/function, and adiposity in stage A HF with no independent or additive effect of n-3 FA administration. (Improving Metabolic Health in Patients With Diastolic Dysfunction [MTG]; NCT03448185).
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Ácidos Graxos Ômega-3 , Insuficiência Cardíaca , Treinamento Intervalado de Alta Intensidade , Adulto , Exercício Físico , Ácidos Graxos Ômega-3/uso terapêutico , Treinamento Intervalado de Alta Intensidade/métodos , Humanos , Pessoa de Meia-Idade , Obesidade/complicaçõesRESUMO
IMPORTANCE: Astronauts returning from long-duration spaceflight experience ocular remodeling related to cephalad fluid shifts induced by microgravity. It is hypothesized that the absence of diurnal reductions in intracranial pressure in microgravity creates a low but persistent pressure gradient at the posterior aspect of the eye, which results in ocular remodeling and space-associated neuro-ocular syndrome (SANS) over many months. OBJECTIVE: To determine whether partial reintroduction of footward fluid shifts during simulated microgravity via lower body negative pressure (LBNP) during sleep attenuates choroid engorgement, an early marker of ocular remodeling related to SANS. DESIGN, SETTING, AND PARTICIPANTS: Between May 2019 and February 2020, participants with no major cardiovascular, kidney, or ophthalmic disease completed 3 days of supine (0°) bed rest with and 3 days without 8 hours of nightly LBNP in a randomized, crossover design. This single-center investigation took place at the UT Southwestern Medical Center. All analyses were conducted blinded to condition and time point. INTERVENTIONS: Eight hours of nightly LBNP (-20 mm Hg) vs no LBNP. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in choroid area and volume after 3 days of bed rest measured by optical coherence tomography. RESULTS: Of 10 participants, 5 were female, the mean (SD) age was 29 (9) years, and the age range was 18 to 55 years. Central venous pressure increased from the seated to supine position (mean [SD], seated: -2.3 [2.0] vs supine: 6.9 [2.0] mm Hg; P < .001), leading to choroid engorgement over 3 days of bed rest (Δ area: +0.09 mm2 [95% CI, 0.04-0.13]; P = .001; Δ volume: +0.37 mm3 [95% CI, 0.19-0.55]; P = .001). Nightly LBNP caused a sustained reduction in supine central venous pressure (mean [SD], 5.7 [2.2] mm Hg to 1.2 [1.4 mm Hg]; P < .001) and attenuated the increase in choroid area (74%) (Δ: 0.02 mm2 [95% -0.02 to 0.06]; P = .01) and volume (53%) (Δ: 0.17 mm3 [95% CI, 0.01-0.34]; P = .05) compared with control. CONCLUSIONS AND RELEVANCE: Nightly LBNP reinstated a footward fluid shift and mitigated the increase in choroid area and volume. LBNP during sleep may be an effective countermeasure for ocular remodeling and SANS during long-duration space missions.
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Hiperemia , Voo Espacial , Ausência de Peso , Adolescente , Adulto , Astronautas , Corioide , Estudos Cross-Over , Feminino , Humanos , Pressão Negativa da Região Corporal Inferior , Masculino , Pessoa de Meia-Idade , Síndrome , Adulto JovemRESUMO
AIMS: Left ventricular (LV) restoring forces are primed by ventricular deformation during systole and contribute to cardiac relaxation and early diastolic suction. Systolic-diastolic coupling, the relationship between systolic contraction and diastolic recoil, is a novel marker of restoring forces, but the effect of left atrial pressure (LAP) is unknown. We tested preliminary methods of systolic-diastolic coupling comparing mitral annular velocities versus excursion distances and hypothesized a recoil/contraction distance ratio would remain unaffected across varying LAP, providing a surrogate for quantifying LV restoring forces. METHODS AND RESULTS: Healthy subjects (n = 61, age 52 ± 5 years) underwent manipulation of LAP with lower body negative pressure (LBNP) and rapid normal saline (NS) infusion. Pulmonary capillary wedge pressure (PCWP; pulmonary artery catheter) and tissue Doppler imaging of the mitral annulus were measured. Two models of systolic-diastolic coupling--early diastolic excursion (EDexc )/systolic contraction (Sexc ) distances and e'/systolic (s') velocities were compared. Velocity (e'/s') coupling ratios varied significantly (mean e'/s', slope = 0.022, p < 0.001) in relationship with PCWP (5-20 mmHg). Excursion (EDexc /Sexc ) coupling ratio did not vary in relationship with PCWP (EDexc /Sexc : slope = -0.001, p = 0.19). CONCLUSIONS: Systolic-diastolic coupling using mitral annular distance ratios to standardize early diastolic recoil to systolic contraction was not significantly impacted by LAP, in contrast to coupling ratios using velocities. The pressure invariance of annular distance coupling ratios suggests this metric quantifies the efficiency of LV restoring forces by isolating systolic contributions to early diastolic restoring forces independent from changes in LAP.
Assuntos
Diástole/fisiologia , Sístole/fisiologia , Função Ventricular Esquerda/fisiologia , Ecocardiografia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Individuals with left ventricular (LV) hypertrophy and elevated cardiac biomarkers in middle age are at increased risk for the development of heart failure with preserved ejection fraction. Prolonged exercise training reverses the LV stiffening associated with healthy but sedentary aging; however, whether it can also normalize LV myocardial stiffness in patients at high risk for heart failure with preserved ejection fraction is unknown. In a prospective, randomized controlled trial, we hypothesized that 1-year prolonged exercise training would reduce LV myocardial stiffness in patients with LV hypertrophy. METHODS: Forty-six patients with LV hypertrophy (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomly assigned to either 1 year of high-intensity exercise training (n=30) or attention control (n=16). Right-heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using both lower body negative pressure and rapid saline infusion to define the LV end-diastolic pressure-volume relationship. A constant representing LV myocardial stiffness was calculated from the following: P=S×[Exp {a (V-V0)}-1], where "P" is transmural pressure (pulmonary capillary wedge pressure - right atrial pressure), "S" is the pressure asymptote of the curve, "V" is the LV end-diastolic volume index, "V0" is equilibrium volume, and "a" is the constant that characterizes LV myocardial stiffness. RESULTS: Thirty-one participants (exercise group [n=20]: 54±6 years, 65% male; and controls (n=11): 51±6 years, 55% male) completed the study. One year of exercise training increased max by 21% (baseline 26.0±5.3 to 1 year later 31.3±5.8 mL·min-1·kg-1, P<0.0001, interaction P=0.0004), whereas there was no significant change in max in controls (baseline 24.6±3.4 to 1 year later 24.2±4.1 mL·min-1·kg-1, P=0.986). LV myocardial stiffness was reduced (right and downward shift in the end-diastolic pressure-volume relationship; LV myocardial stiffness: baseline 0.062±0.020 to 1 year later 0.031±0.009), whereas there was no significant change in controls (baseline 0.061±0.033 to 1 year later 0.066±0.031, interaction P=0.001). CONCLUSIONS: In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03476785.
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Exercício Físico/fisiologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/terapia , Volume Sistólico/fisiologia , Teste de Esforço/métodos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Renal denervation (RDN) is effective at lowering blood pressure. However, it is unknown if ablative procedures elicit sympathetic denervation of the kidneys in humans. The aim of this investigation was to assess sympathetic innervation of the renal cortex following perivascular chemical RDN, which may be particularly effective at ablating perivascular efferent and afferent nerves. METHODS: Seven hypertensive patients (4F:3M; 50-65 years) completed PET-CT sympathetic neuroimaging of the renal cortex using 11C-methylreboxetine (11C-MRB, norepinephrine transporter ligand) and 6-[18F]-fluorodopamine (18F-FDA; substrate for the cell membrane norepinephrine transporter) before and 8 weeks after chemical RDN (Peregrine System Infusion Catheter, Ablative Solutions; n = 4; 2F:2M) or control renal angiography (n = 3; 2F:1M). Patients completed physiological phenotyping including 24-hour ambulatory blood pressure, hemodynamics, muscle sympathetic nerve activity, and 24-hour urine collection. RESULTS: RDN decreased 11C-MRB-derived radioactivity by ~30% (Δââ11C-MRB/chamber: -0.95 a.u. confidence interval (CI): -1.36 to -0.54, P = 0.0002), indicative of efferent RDN. In contrast, 18F-FDA-derived radioactivity increased (Δââ18F-FDA/chamber: 2.72 a.u. CI: 0.73-4.71, P = 0.009), consistent with reduced vesicular turnover. Controls showed no change in either marker. Ambulatory systolic pressure decreased in 3 of 4 patients (-9 mm Hg CI: -27 to 9, P = 0.058), and central systolic pressure decreased in all patients (-23 mm Hg CI: -51 to 5, P = 0.095). CONCLUSIONS: These results are the first to show efferent sympathetic denervation of the renal cortex following RDN in humans. Further studies of mechanisms underlying variable blood pressure lowering in the setting of documented RDN may provide insights into inconsistencies in clinical trial outcomes. CLINICAL TRIALS REGISTRATION: Trial Number NCT03465917.
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Denervação , Hipertensão , Rim , Idoso , Denervação/métodos , Feminino , Humanos , Hipertensão/terapia , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Simpatectomia , Resultado do TratamentoRESUMO
BACKGROUND: Age-related changes to left ventricular (LV) early diastolic recoil confound the diagnostic value of e' velocity in heart failure with preserved ejection fraction (HFpEF). Systolic-diastolic coupling quantifies passive left ventricular elastic recoil and may be superior to e' in differentiating abnormal diastolic recoil in HFpEF from healthy aging. This study aims to determine the effect of healthy aging and HFpEF on systolic-diastolic coupling. METHODS: Healthy adults (n = 141, aged 20-90 years) underwent right heart catheterization (RHC) to quantify LV filling pressure and tissue Doppler echocardiography to define peak velocities and excursion (velocity time integral) of the mitral annulus. Separately, HFpEF patients (n = 12, age 67 ± 5 years) and controls (n = 12, age 68 ± 5 years) underwent RHC and echocardiography. Systolic-diastolic coupling was measured as early diastolic excursion (EDexc ) divided by systolic excursion (Sexc ). RESULTS: In healthy adults, EDexc / Sexc declined by 15% per decade of life (r2 = 0.53, P < .001). EDexc /Sexc was significantly lower in HFpEF compared with controls (0.43 ± 0.11 vs 0.56 ± 0.11, P = .011), while e' was similar (6.2 ± 1.5 vs 6.8 ± 1.3 cm/s, P = .33). Using ROC analysis, EDexc /Sexc had an AUC to detect HFpEF of 0.82 (0.61-0.95, P = .007), which was superior to e' alone (AUC 0.60(0.39-0.80), P = .39; P = .026 for difference). CONCLUSIONS: Systolic-diastolic coupling, quantified by the EDexc /Sexc ratio, declined linearly with healthy aging. The EDexc /Sexc ratio was further reduced in HFpEF and able to predict HFpEF more accurately than e' alone. Systolic-diastolic coupling may be a useful diagnostic tool to detect HFpEF.
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Envelhecimento Saudável , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Adulto , Idoso , Diástole , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Volume Sistólico , Sístole , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular EsquerdaRESUMO
Astronauts have presented with a constellation of visual changes referred to as spaceflight-associated neuro-ocular syndrome (SANS). However, neither have early markers of microgravity-induced optic remodeling been fully identified nor have countermeasures been developed. To identify early markers of SANS, we studied 10 subjects with optical coherence tomography and ultrasonography when upright and supine and again after 24 h of 6° head-down tilt (HDT) bed rest. Upon acute transition from the upright to the supine position, choroid area (2.24 ± 0.53 to 2.28 ± 0.52 mm2, P = 0.001) and volume (9.51 ± 2.08 to 9.73 ± 2.08 mm3, P = 0.002) increased. After 24 h of HDT bed rest, subfoveal choroidal thickness (372 ± 93 to 381 ± 95 µm, P = 0.02), choroid area (2.25 ± 0.52 to 2.33 ± 0.54 mm2, P = 0.08), and volume (9.64 ± 2.03 to 9.82 ± 2.08 mm3, P = 0.08) increased relative to the supine position. Subsequently, seven subjects spent 3 days in -6°HDT bed rest to assess whether low-level lower body negative pressure (LBNP) could prevent the observed choroidal engorgement during bed rest. Maintaining the -6° HDT position for 3 days caused choroid area (Δ0.11 mm2, P = 0.05) and volume (Δ0.45 mm3, P = 0.003) to increase. When participants also spent 8 h daily under -20 mmHg LBNP, choroid volume still increased, but substantially (40%) less than in the control trial (Δ0.27 mm3, P = 0.05). Moreover, the increase in choroid area was diminished (Δ0.03 mm2, P = 0.13), indicating that low-level LBNP attenuates the choroid expansion associated with 3 days of -6° HDT bed rest. These data suggest that low-level LBNP may be an effective countermeasure for SANS.NEW & NOTEWORTHY Choroid measurements appear to be sensitive to changes in gravitational gradients, as well as periods of head-down tilt (HDT) bed rest, suggesting that they are potential indicators of early ocular remodeling and could serve to evaluate the efficacy of countermeasures for SANS. Eight hours of lower body negative pressure (LBNP) daily attenuates the choroid expansion associated with 3 days of strict -6° HDT bed rest, indicating that LBNP may be an effective countermeasure for SANS.
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Repouso em Cama , Decúbito Inclinado com Rebaixamento da Cabeça , Repouso em Cama/efeitos adversos , Deslocamentos de Líquidos Corporais , Humanos , Pressão Negativa da Região Corporal Inferior , Simulação de Ausência de PesoRESUMO
BACKGROUND: Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high-risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated left ventricular (LV) myocardial stiffness in comparison with healthy controls as a key marker for future HFpEF. METHODS: Forty-six patients with LVH (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or troponin T [>0.6 pg/mL]) were recruited, along with 61 age- and sex-matched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion. RESULTS: There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (eg, pulmonary capillary wedge pressure: LVH, 13.4±2.7 versus control, 11.7±1.7 mm Hg, P<0.0001). The LV was less distensible in LVH than in controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (pulmonary capillary wedge pressure - right atrial pressure), LV myocardial stiffness was nearly 30% greater in LVH than in controls (LVH stiffness constant, 0.053±0.027 versus controls, 0.042±0.020, P=0.028). CONCLUSIONS: LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than in age- and sex-matched controls and thus appears to represent a transitional state from a normal healthy heart to HFpEF. Although the LV myocardial stiffness of patients with LVH is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high-risk individuals. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03476785 and NCT02039154.
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Insuficiência Cardíaca/patologia , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Ecocardiografia , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Índice de Gravidade de Doença , Volume Sistólico , Troponina T/sangueRESUMO
Background: Increased visceral adipose tissue (VAT) is strongly associated with cardiometabolic risk factors. Accurate quantification of VAT is available through magnetic resonance imaging (MRI), which incurs a significant financial and time burden. We aimed to assess the accuracy of dual-energy X-ray absorptiometry- (DXA-) derived VAT (DXA-VAT) against a gold standard MRI protocol (MRI-VAT) in children with normal weight and obesity cross-sectionally, and over the course of a lifestyle intervention. Methodology: MRI-VAT and DXA-VAT were quantified in 61 children (30 normal weight and 31 with obesity) at baseline. Children with obesity entered a three-month exercise and/or nutrition intervention after which VAT was reassessed. MRI- and DXA-VAT cross-sectional area, volume, and mass were quantified, and associations were calculated at baseline (n = 61) and pre-post intervention (n = 28, 3 participants dropped out). Method agreement was assessed through Bland-Altman analysis, linear regression, and Passing-Bablok regression. Results: At baseline, all DXA- and MRI-VAT outcomes were strongly associated (r = 0.90, P < 0.001). However, there were no significant associations between absolute or relative change in DXA- and MRI-VAT outcomes (r = 0.25-0.36, P > 0.05). DXA significantly overestimated VAT CSA (cross-sectional area), volume, and mass when compared with MRI (P < 0.001) at baseline. Significant proportional bias was observed for all DXA-VAT outcomes at baseline and for relative longitudinal changes in DXA-VAT. Conclusions: Although DXA-VAT outcomes were strongly associated with MRI-VAT outcomes at baseline, estimates were subject to proportional bias in children with obesity and normal weight. DXA lacks validity for detecting changes in VAT among children with obesity. This trial is registered with NCT01991106.
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Absorciometria de Fóton , Gordura Intra-Abdominal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Obesidade Infantil/diagnóstico por imagem , Adolescente , Composição Corporal , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/fisiopatologia , Estudos Longitudinais , Masculino , Obesidade Infantil/fisiopatologia , Reprodutibilidade dos Testes , Comportamento de Redução do RiscoRESUMO
This study aimed to quantify the sedative effects, detection rates, and cardiovascular responses to xenon. On 3 occasions, participants breathed xenon (FiXe 30% for 20 min; FiXe 50% for 5 min; FiXe 70% for 2 min) in a nonblinded design. Sedation was monitored by a board-certified anesthesiologist. During 70% xenon, participants were also verbally instructed to operate a manual value with time-to-task failure being recorded. Beat-by-beat hemodynamics were measured continuously by ECG, photoplethysmography, and transcranial Doppler. Over 48 h postadministration, xenon was measured in blood and urine by gas chromatography-mass spectrometry. Xenon caused variable levels of sedation and restlessness. Task failure of the self-operating value occurred at 60-90 s in most individuals. Over the first minute, 50% and 70% xenon caused a substantial reduction in total peripheral resistance (P < 0.05). All dosages caused an increase in cardiac output (P < 0.05). By the end of xenon inhalation, slight hypertension was observed after all three doses (P < 0.05), with an increase in middle cerebral artery velocity (P < 0.05). Xenon was consistently detected, albeit in trace amounts, up to 3 h after all three doses of xenon inhalation in blood and urine with variable results thereafter. Xenon inhalation caused sedation incompatible with self-operation of a breathing apparatus, thus causing a potential life-threatening condition in the absence of an anesthesiologist. Yet, xenon can only be reliably detected in blood and urine up to 3 h postacute dosing.NEW & NOTEWORTHY Breathing xenon in dosages conceivable for doping purposes (FiXe 30% for 20 min; FiXe 50% for 5 min; FiXe 70% for 2 min) causes an initial rapid fall in total peripheral resistance with tachycardia and thereafter a mild hypertension with elevated middle cerebral artery velocity. These dose duration intervals cause sedation that is incompatible with operating a breathing apparatus and can only be detected in blood and urine samples with a high probability for up to ~3 h.
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Hemodinâmica/efeitos dos fármacos , Esportes/fisiologia , Xenônio/administração & dosagem , Administração por Inalação , Adulto , Anestésicos Inalatórios/administração & dosagem , Circulação Cerebrovascular/efeitos dos fármacos , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Masculino , Ultrassonografia Doppler Transcraniana/métodosRESUMO
This study aimed to assess the efficacy of acute subanesthetic dosages of xenon inhalation to cause erythropoiesis and determine the effect of chronic xenon dosing on hematological parameters and athletic performance. To assess the acute effects, seven subjects breathed three subanesthetic concentrations of xenon: 30% fraction of inspired xenon (FiXe) for 20 min, 50% FiXe for 5 min, and 70% FiXe for 2 min. Erythropoietin (EPO) was measured at baseline, during, and after xenon inhalation. To determine the chronic effects, eight subjects breathed 70% FiXe for 2 min on 7 consecutive days, and EPO, total blood, and plasma volume were measured. Phase II involved assessment of 12 subjects for EPO, total blood volume, maximal oxygen uptake, and 3-km time before and after random assignment to 4 wk of xenon or sham gas inhalation. FiXe 50% and 70% stimulated an increase in EPO at 6 h [+2.3 mIU/mL; 95% confidence interval (CI) 0.1-4.5; P = 0.038] and at 192 h postinhalation (+2.9 mIU/mL; 95% CI 0.6-5.1; P = 0.017), respectively. Seven consecutive days of dosing significantly elevated plasma volume (+491 mL; 95% CI 194-789; P = 0.002). Phase II showed no significant effect on EPO, hemoglobin mass, plasma volume, maximal oxygen uptake, or 3-km time. Acute exposure to subanesthetic doses of xenon caused a consistent increase in EPO, and 7 consecutive days of xenon inhalation significantly expanded plasma volume. However, this physiological response appeared to be transient, and 4 wk of xenon inhalation did not stimulate increases in plasma volume or erythropoiesis, leaving cardiorespiratory fitness and athletic performance unchanged.NEW & NOTEWORTHY This is the first study to examine each element of the cascade by which xenon inhalation is purported to take effect, starting with measurement of the hypoxia-inducible factor effector, erythropoietin, to hemoglobin mass and blood volume and athletic performance. We found that acute exposure to xenon increased serum erythropoietin concentration, although major markers of erythropoiesis remained unchanged. While daily dosing significantly expanded plasma volume, no physiological or performance benefits were apparent following 4 wk of dosing.
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Desempenho Atlético/fisiologia , Eritropoetina/metabolismo , Xenônio/administração & dosagem , Adulto , Eritropoese/efeitos dos fármacos , Feminino , Hemoglobinas/metabolismo , Humanos , Hipóxia/metabolismo , Masculino , Volume Plasmático/efeitos dos fármacosRESUMO
OBJECTIVE: The time needed to increase oxygen utilisation to meet metabolic demand (VÌO2 kinetics) is impaired in heart failure (HF) with reduced ejection fraction and is an independent risk factor for HF mortality. It is not known if VÌO2 kinetics are slowed in HF with preserved ejection fraction (HFpEF). We tested the hypothesis that VÌO2 kinetics are slowed during submaximal exercise in HFpEF and that slower VÌO2 kinetics are related to impaired peripheral oxygen extraction. METHODS: Eighteen HFpEF patients (68±7 years, 10 women) and 18 healthy controls (69±6 years, 10 women) completed submaximal and peak exercise testing. Cardiac output (acetylene rebreathing, QÌc), ventilatory oxygen uptake (VÌO2, Douglas bags) and arterial-venous O2 difference (a-vO2 difference) derived from QÌc and VÌO2 were assessed during exercise. Breath-by-breath O2 uptake was measured continuously throughout submaximal exercise, and VÌO2 kinetics was quantified as mean response time (MRT). RESULTS: HFpEF patients had markedly slowed VÌO2 kinetics during submaximal exercise (MRT: control: 40.1±14.2, HFpEF: 65.4±27.7 s; p<0.002), despite no relative impairment in submaximal cardiac output (QÌc: control: 8.6±1.7, HFpEF: 9.7±2.2 L/min; p=0.79). When stratified by MRT, HFpEF with an MRT ≥60 s demonstrated elevated QÌc, and impaired peripheral oxygen extraction that was apparent during submaximal exercise compared with HFpEF with a MRT <60 s (submaximal a-vO2 difference: MRT <60 s: 9.7±2.1, MRT ≥60 s: 7.9±1.1 mL/100 mL; p=0.03). CONCLUSION: HFpEF patients have slowed VÌO2 kinetics that are related to impaired peripheral oxygen utilisation. MRT can identify HFpEF patients with peripheral limitations to submaximal exercise capacity and may be a target for therapeutic intervention.