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Background Arterial stiffness and earlier wave reflections can increase afterload and impair cardiovascular function. Most prior studies have been performed in patients with preserved left ventricular function. We describe novel measures of pulsatile arterial hemodynamics and their association with clinical outcomes in patients with heart failure with reduced ejection fraction. Methods and Results Participants with heart failure with reduced ejection fraction (n=137, median age 56 years, 49% women, 58% Black) and age-matched healthy controls (n=124) underwent measurements of large artery stiffness and pulsatile arterial hemodynamics. Carotid-femoral pulse wave velocity and augmentation index were assessed using radial applanation tonometry. Pressure-flow analyses derived reflected wave transit time, the systolic pressure-time integral imposed by proximal aortic characteristic impedance, and the pressure-time integral from wave reflection (wasted pressure effort). Cox proportional hazards models defined associations between hemodynamic measures and (1) all-cause death and (2) a combined end point of left ventricular assist device implant, heart transplant, and death, at 2 years adjusted for race, BNP (B-type natriuretic peptide), and the Meta-Analysis Global Group in Chronic Heart Failure Risk Score. Compared with controls, participants with heart failure with reduced ejection fraction exhibited similar carotid-femoral pulse wave velocity (6.8±1.6 versus 7.0±1.6 m/s, P=0.40) but higher augmentation index normalized to a heart rate of 75 bpm (13±2% versus 22±2%, P<0.001). Shorter reflected wave transit time (ie, earlier wave reflection arrival to the proximal aorta) was associated with an increased risk of death (adjusted hazard ratio [aHR] 1.67 [95% CI 1.03-1.63]) and the combined end point of death/left ventricular assist device/heart transplant (aHR, 1.61 [95% CI, 1.06-2.44]) at 2 years. Wasted pressure effort/proximal aortic characteristic impedance, representing the proportion of systolic load from wave reflection versus aortic root characteristic impedance, was univariately associated with death (hazard ratio (HR), 1.44 [95% CI, 1.05-1.97]) and with death/left ventricular assist device/heart transplant on univariate (HR, 1.42 [95% CI, 1.07-1.88]) and multivariable (aHR, 1.40 [95% CI, 1.02-1.93]) analysis. Conclusions Increased left ventricular systolic load from premature wave reflections is associated with adverse clinical outcomes in patients with heart failure with reduced ejection fraction.

Asunto(s)

Insuficiencia Cardíaca , Rigidez Vascular , Disfunción Ventricular Izquierda , Humanos , Femenino , Persona de Mediana Edad , Masculino , Análisis de la Onda del Pulso , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Presión Sanguínea/fisiología , Hemodinámica , Rigidez Vascular/fisiología , Aorta

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RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

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Insuficiencia Renal Crónica , Enfermedades Vasculares , Humanos , Fuerza de la Mano , Espectroscopía Infrarroja Corta/métodos , Análisis de la Onda del Pulso , Grosor Intima-Media Carotídeo , Estudios Transversales , Músculo Esquelético/metabolismo , Enfermedades Vasculares/metabolismo , Consumo de Oxígeno/fisiología

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BACKGROUND: Pressure wave reflections (PWRs) within the circulation are assessed at various arterial sites by various noninvasive methods. We aimed at reviewing the conflicting data regarding the hypothesis that higher PWRs are associated with higher left ventricular mass and tested whether this association stands for all available indices of PWRs, all (proximal or distal to the heart) sites of assessment, and is modified by sex, age and heart rate. METHODS: Based on a predefined protocol applying the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we identified eligible for meta-analysis data regarding: augmentation index, augmentation pressure, backward pressure (Pb), reflection index, and their association with left ventricular mass index (19 studies, total population n=8686). RESULTS: We found statistically significant associations, independent from blood pressure level, for all indices of PWRs at all arterial sites (carotid augmentation index; odds ratio; standardized beta coefficient [ß]: 0.14 [95% CI, 0.07% to 0.21%], per SD increase), radial augmentation index (ß: 0.21; 0.11 to 0.31), central augmentation pressure (ß: 0.15; 0.03 to 0.27), central Pb (ß: 0.23; 0.05 to 0.42), and central reflection index (ß: 0.14; 0.06 to 0.22), except for aortic augmentation index as estimated by generalized transfer functions. Meta-regression analysis showed that the association between carotid augmentation index and left ventricular mass was higher among populations with higher heart rate (P=0.036, beta: 0.017 [95% CI, 0.001 to 0.033]) and tended to be higher in middle-aged (P=0.07, beta: -0.001; -0.021 to 0.001). CONCLUSIONS: A clinically meaningful association between PWRs and left ventricular mass, assessed at either central or peripheral arterial sites by most available methods was shown, suggesting that PWR reduction strategies might be useful. Based on the present evidence, such trials should target middle-aged populations with high normal heart rate.

Asunto(s)

Arterias Carótidas , Plomo , Presión Sanguínea/fisiología , Frecuencia Cardíaca , Análisis de Regresión , Análisis de la Onda del Pulso

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Coronary artery disease (CAD) is the leading cause of human death and has a high prevalence throughout the world. Therefore, it is important to detect CAD early and to apply individualized therapy according to the patients' risk. There is an increasing interest in pulsatile arterial hemodynamics in the cardiovascular area. Widely used measurements of arterial pulsatile hemodynamics include pulse pressure, pulse wave velocity and augmentation index. Here, we will review underlying pathophysiology linking the association of arterial pulsatile hemodynamics with CAD, and the usefulness of the measurements of pulsatile hemodynamics in the prediction of future cardiovascular events of CAD patients. Clinical and therapeutic implications will be also addressed.

RESUMEN

Preeclampsia is a worldwide pregnancy complication with serious short- and long-term maternal and neonatal consequences. Our understanding of preeclampsia pathophysiology has significantly evolved over the last decades with the recognition that impaired arterial function and structure may occur early in the course of pregnancy, preceding the clinic-humoral syndrome and driving long-term cardiovascular disease risk in the future of these patients. Although an early abnormal placentation may be the inciting event for a large proportion of cases, there is growing evidence that challenges the placental hypothesis in all affected women, since placental histopathology lesions thought to be characteristic are neither sensitive nor specific markers for the disorder. Recent hemodynamic investigations and studies on left ventricular function and structure in women with preeclampsia further challenge this universal paradigm and propose that placental dysfunction could be secondary to a maternal cardiovascular maladaptation to pregnancy in certain patients. Supporting this hypothesis, certain vascular features, which are characteristically enhanced in normal pregnancy allowing a healthy vascular adaptation, are absent in preeclampsia and comparable to the nonpregnant population. However, arterial biomechanics in preeclampsia may only not cope with hemodynamic demands of pregnancy but also impose additional detrimental loads to the maternal heart ("impaired left-ventricle-aorta coupling") and transmit pressure and flow disturbances into the fetoplacental circulation ("impaired large arteries-microcirculation coupling"). In this review, we analyze the major role of the arterial dysfunction in the cardiovascular maladaptation hypothesis of preeclampsia, shed light on its potential etiopathogenic link, and discuss the complementary nature of the placental and cardiovascular theories.

Asunto(s)

Arterias/fisiopatología , Endotelio Vascular/fisiopatología , Hemodinámica/fisiología , Preeclampsia/fisiopatología , Rigidez Vascular/fisiología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Placenta/irrigación sanguínea , Embarazo

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BACKGROUND: Hemolysis in sickle cell disease (SCD) releases cell free hemoglobin, which scavenges nitric oxide (NO), leading to pulmonary vascular vasoconstriction, increased pulmonary vascular resistance (PVR), and the development of PH. However, PVR is only one component of right ventricular (RV) afterload. Whether sickled red blood cells increase the total RV afterload, including compliance and wave reflections, is unclear. OBJECTIVE: Patients with SCD and pulmonary hypertension (PH) have a significantly increased risk of sudden death compared to patients with SCD alone. Sickled red blood cells (RBCs) are fragile and lyse easily. Here, we sought to determine the acute effects of SCD RBCs and increased cell free hemoglobin on RV afterload. METHODS: Main pulmonary artery pressures and flows were measured in C57BL6 mice before and after exchanges of whole blood (~200 uL, Hct=45%) with an equal volume of SCD RBCs in plasma (Hct=45%) or cell free hemoglobin (Hb+) in solution. After transfusions, animals were additionally stressed with acute hypoxia (AH; 10% O2). RESULTS: SCD RBCs increased PVR only compared to control RBCs; cell free hemoglobin increased PVR and wave reflections. These increases in RV afterload increased further with AH. CONCLUSIONS: The release of cell free hemoglobin from fragile SCD RBCs in vivo increases the total RV afterload and may impair RV function more than the SCD RBCs themselves.

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BACKGROUND: Lipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD). METHODS: Three hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels. RESULTS: After dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 µg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 µg/L and in the 1st tertile (Lp-PLA2 values < 101 µg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 µg/L. A linear regression analysis showed that Lp-PLA2 values > 138 µg/L negatively correlated to FMD [b = - 0.45 (95% CI: - 0.79 - -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57-3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with ß-blockers. CONCLUSIONS: Elevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.

Asunto(s)

1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Enfermedad de la Arteria Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Rigidez Vascular/fisiología , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad

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Cerebral pulsatility reflects a balance between the transmission and damping of pulsatility in the cerebrovasculature. Females experience greater cerebral pulsatility with aging, which may have implications for sex differences in stroke risk and cognitive decline. This study sought to explore vascular contributors to cerebral pulsatility and pulsatile damping in men and women. Adults (n = 282, 53% female) underwent measurements of cerebral (middle cerebral artery) pulsatility, pulsatile damping (ratio of cerebral to carotid pulsatility), large artery stiffening (ratio of aortic to carotid pulse wave velocity), and carotid wave transmission/reflection dynamics using wave intensity analysis. Multiple regression revealed that older age, female sex, greater large artery stiffening, higher carotid pulse pressure, and greater forward wave energy was associated with increased cerebral pulsatility (adjusted R2 = 0.44, P < 0.05). Contributors to decreased cerebral pulsatile damping included older age, female sex, and lower wave reflection index (adjusted R2 = 0.51, P < 0.05). Our data link greater large artery stiffening, carotid pulse pressure, and forward wave energy to greater cerebral pulsatility, while greater carotid wave reflection may enhance cerebral pulsatile damping. Lower cerebral pulsatile damping among females may contribute to greater age-associated cerebral pulsatile burden compared with males.NEW & NOTEWORTHY Cerebral pulsatility contributes to brain health and depends on a balance between transmission and damping of pulsatile hemodynamics into the cerebrovasculature. Our data indicate that cerebral pulsatility increases with age, female sex, extracranial artery stiffening, forward wave energy, and pulse pressure, whereas pulsatile damping decreases with age and female sex and increases with greater carotid wave reflections. These novel data identify pulsatile damping as a potential contributor to sex differences in cerebral pulsatile burden.

Asunto(s)

Grosor Intima-Media Carotídeo , Flujo Pulsátil , Análisis de la Onda del Pulso , Rigidez Vascular , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Arterias Carótidas , Femenino , Humanos , Masculino

RESUMEN

Using high-fidelity micromanometers and flow velocity sensors at right heart catheterization, we compared pulmonary hemodynamics and wave reflections in age-matched normal adults and those with atrial septal defects, separated into three subgroups based on levels of mean pulmonary artery pressure: low (<17 mmHg), intermediate (17-26 mmHg), high (>26 mmHg). We made baseline measurements in all groups and after intravenous sodium nitroprusside in the subgroups. All of the subgroups had higher than normal baseline pulmonary flows and corresponding power that did not differ among the subgroups. The pulmonary vascular resistance, input resistance, and characteristic impedance in the subgroups did not differ from normal. Aside from the elevated flow and power, the hemodynamics in the low subgroup did not differ from normal. The intermediate subgroup had significantly higher than normal right ventricular and pulmonary artery pressures, wave reflections, and shorter wave reflection time, which all reverted to normal after nitroprusside. The high subgroup had similar changes as the intermediate subgroup. Unlike that subgroup, however, the pressures, wave reflections, and reflection return time did not revert to normal after nitroprusside. Hence, elevated wave reflections, but not resistance or characteristic impedance, are the hallmark of pulmonary hypertension in adults with atrial septal defects. Our results demonstrate that detailed measurements of hemodynamics and assessment of responsiveness to vasodilators provide important information about the pulmonary circulation in atrial septal defect. Coupled with studies after defect closure, those results may be a better foundation than current ones for clinical decisions.

Asunto(s)

Defectos del Tabique Interatrial/fisiopatología , Hemodinámica , Circulación Pulmonar , Adulto , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Nitroprusiato/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiopatología , Vasodilatadores/farmacología

RESUMEN

BACKGROUND: Augmentation index (AIx) is used to quantify the augmented systolic aortic pressure that impedes ventricular ejection. Its use as an index of wave reflections is questionable. We hypothesize that AIx is quantitatively different from the reflection coefficient under varied physiological conditions. METHODS: 42 datasets of aortic pressure and flow waveforms were obtained during induced hypertension (methoxamine infusion) and vasodilation (nitroprusside infusion) in our mongrel dog experiments (n = 5) and from Mendeley data during various interventions (vasoconstrictors, vasodilators, pacing, stimulation, hemorrhage and hemodilution). Wave reflections and principal components of reflection coefficients were computed for comparison to AIx and heart rate normalized AIx. RESULTS: Principal reflection coefficient, Γ1, increased in hypertension and decreased in vasodilation, hemorrhage and hemodilution. AIx followed the trend in many cases but was consistently lower than Γ1 in almost all the subjects. The Bland-Altman analysis also showed that both AIx and normalized AIx underestimated Γ1. The relationship between augmentation index and reflection coefficient was explained by a linear regression model (r2 = 0.23, p < 0.01) in which AIx followed directional changes in Γ1 and the normalization of AIx resulted in a linear model that explained less variation in the relationship between AIx and Γ1. CONCLUSION: AIx is a reasonable clinical trend indicator, albeit not an accurate surrogate measure of the amount of wave reflections.

Asunto(s)

Presión Sanguínea , Hemorragia/fisiopatología , Hipertensión/fisiopatología , Modelos Cardiovasculares , Sístole , Vasodilatación , Animales , Bases de Datos Factuales , Perros , Hemodilución , Humanos , Hipertensión/inducido químicamente , Metoxamina/efectos adversos , Metoxamina/farmacología , Nitroprusiato/farmacología , Análisis de la Onda del Pulso

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BACKGROUND: Increased pulse wave reflections in hypertension arise due to impedance mismatching and the effective energy transmission to the vasculature is compromised. Their quantification in the time and the frequency domains are compared and the beneficial effect of vasodilator is evaluated in the study. METHODS: A simple, fast time domain method for the resolution of aortic pressure and flow pulses into their forward and reflected components is presented, together with frequency domain reflection coefficient and impedance calculations. Both steady and pulsatile energy components are quantified during induced hypertension (HBP) and subsequent vasodilator (VSD, nitroprusside) treatment in experimental mongrel dogs. Corresponding power generation and usage are also analyzed. RESULTS: Characteristic impedance and peripheral resistance were not statistically different between the methods (p > 0.05). Time domain reflection coefficient identified significant differences among control, HBP and VSD groups (p < 0.05) while the frequency domain method did not adequately differentiate the control and the HBP groups. Impedance calculations were similar between the two methods. Frequency domain calculations of total, mean and pulsatile power were, on average, 32.6 mW higher, 12.8 mW lower and 45.4 mW higher than their respective time domain calculations (p < 0.05). Hypertension increased energy consumption, on average, by 88.8 mJ (p < 0.05) and subsequent VSD decreased the energy consumption, on average, by 99.4 mJ (p < 0.05). CONCLUSION: Impedance mismatching in hypertension which leads to increased wave reflections and significantly increased pulsatile work, could be effectively alleviated through vasodilator therapy. This can be quantified through the time-domain method, which is fast and equally accurate as the time-consuming frequency domain approach. The time domain method to quantify crucial parameters such as stroke work cannot be readily determined using the frequency domain methods.

Asunto(s)

Impedancia Eléctrica , Hipertensión , Nitroprusiato/farmacología , Análisis de la Onda del Pulso , Resistencia Vascular/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Modelos Animales de Enfermedad , Perros , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología

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Background The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement ( AVR ). Methods and Results We enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR . Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P=0.002) but not extracellular mass (42.3 versus 40.6 g; P=0.67) was seen after AVR . Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P=0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm5; P=0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR ( R=-0.51; P=0.0026). The 6-minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time ( R=0.52; P=0.01). Conclusions Consistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR . Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population.

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Estenosis de la Válvula Aórtica/diagnóstico , Arterias/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Miocardio/patología , Rigidez Vascular/fisiología , Función Ventricular Izquierda/fisiología , Remodelación Ventricular , Anciano , Estenosis de la Válvula Aórtica/fisiopatología , Arterias/fisiopatología , Presión Sanguínea/fisiología , Femenino , Fibrosis/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética/métodos , Masculino , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad

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BACKGROUND: High blood pressure states (HBP) would differ in wave components and reflections indexes, which could associate clinical and prognostic implications. The study aims: 1) to characterize the association of aortic wave components and reflection parameters (backward [Pb], forward [Pf], Pb/Pf ratio and augmentation index [AIx]) with demographic, anthropometric, hemodynamic and arterial parameters in healthy children and adolescents; 2) to generate multivariate prediction models for the associations, to contribute to understand the main determinants of Pf, Pb, Pb/Pf and AIx; 3) to identify if differences in wave reflection indexes observed in HBP could be explained by differences in the analyzed parameters. METHODS: Healthy children and adolescents (n=816, females: 386; Age: 3-20 years) were studied. EVALUATIONS: central aortic pressure and wave components (Pb, Pf, Pb/Pf and AIx determination with SphygmoCor [SCOR] and Mobil-o-Graph [MOG]); anthropometric assessment; regional arterial stiffness (carotid-femoral, carotid-radial pulse wave velocity [PWV] and PWV ratio); carotid intima-media thickness; carotid and femoral distensbility; cardiac output; systemic vascular resistances (SVR). Simple and multiple regression models were constructed to determine aortic wave parameters; the main explanatory variables. Normotensive and HBP groups were compared. Differences in wave reflection indexes were analyzed before and after controlling for explanatory variables. Equivalences between SphygmoCor and Mobil-O-Graph data were assessed (correlation and Bland-Altman analyses). RESULTS AND CONCLUSION: There were systematic and proportional differences between the data obtained with SphygmoCor and Mobil-O-Graph devices. Heart rate (HR), peripheral pulse pressure, height and weight were the variables that isolated (simple associations) or combined (multiple associations), showed the major capability to explain interindividual differences in Pf, Pb, Pb/Pf and AIx. Arterial stiffness also showed explanatory capacity, being the carotid the artery with the major contribution. HBP associated higher Pf, Pb, AIx and lower Pb/Pf ratio. Those findings were observed together with higher weight, arterial stiffness and HR. After adjusting for anthropometric characteristics, HR, cardiac output and SVR, the HBP group showed greater Pf and Pb. Then, Pf and Pb characteristics associated with HBP would not be explained by anthropometric or hemodynamic factors. Evaluating wave components and reflection parameters could contribute to improve the comprehension and management of HBP states.

Asunto(s)

Aorta/fisiopatología , Presión Arterial , Hipertensión/fisiopatología , Rigidez Vascular , Adolescente , Factores de Edad , Antropometría , Determinación de la Presión Sanguínea , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Frecuencia Cardíaca , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Masculino , Análisis de la Onda del Pulso , Factores de Riesgo , Factores de Tiempo , Adulto Joven

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Isquemia Encefálica , Accidente Cerebrovascular , Presión Sanguínea , Hemodinámica , Humanos , Pronóstico

RESUMEN

High dietary sodium intake can lead to hypertension and increased incidence of cardiovascular disease. We sought to determine the effect of short-term dietary sodium loading on central blood pressure and arterial stiffness in young (YG; 22-40 years) and middle-aged (MA; 41-60 years) normotensive adults. YG (n = 49; age: 27 ± 1 years) and MA (n = 36; age: 52 ± 1 years) subjects were randomized, in a cross-over design, to 7 days of low-sodium (LS; 20 mmol/d) or high-sodium (HS; 300 mmol/d) diet. On the last day of each diet, central pressures, forward and reflected wave amplitudes (via radial artery applanation tonometry), and carotid-femoral pulse wave velocity were assessed. Central systolic blood pressure (cSBP) was greater after HS in both YG (LS: 96 ± 1 vs. HS: 99 ± 1 mm Hg; P = .012) and MA (LS: 106 ± 2 vs. HS: 115 ± 3 mm Hg; P < .001). However, the increase in cSBP was greater in MA (YG: 4 ± 1 vs. MA: 9 ± 2; P = .02). In MA subjects, HS elicited greater forward (LS: 25 ± 1 vs. HS: 29 ± 1 mm Hg; P < .001) and reflected (LS: 19 ± 1 vs. HS: 23 ± 1 mm Hg; P < .001) wave amplitudes. Carotid-femoral pulse wave velocity was also greater in MA on HS but after adjustment for mean arterial pressure, the difference was no longer significant. Our data indicate that HS intake leads to a greater increase in cSBP in MA adults, which may be the result of increased forward and reflected wave amplitudes.

Asunto(s)

Presión Arterial/fisiología , Análisis de la Onda del Pulso , Sodio en la Dieta/efectos adversos , Rigidez Vascular/fisiología , Adulto , Factores de Edad , Determinación de la Presión Sanguínea , Arterias Carótidas/fisiopatología , Estudios Cruzados , Dieta Hiposódica , Femenino , Arteria Femoral/fisiopatología , Humanos , Hipertensión/dietoterapia , Hipertensión/epidemiología , Hipertensión/etiología , Incidencia , Masculino , Persona de Mediana Edad , Adulto Joven

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Measures of interaction between the left ventricle (LV) and arterial system (ventricular-arterial coupling) are important but under-recognised cardiovascular phenotypes in heart failure. Ventriculo-arterial coupling is commonly assessed in the pressure-volume plane, using the ratio of effective arterial elastance (EA) to LV end-systolic elastance (EES) to provide information on ventricular-arterial system mechanical efficiency and performance when LV ejection fraction is abnormal. These analyses have significant limitations, such as neglecting systolic loading sequence, and are less informative in heart failure with preserved ejection fraction (HFpEF). EA is almost entirely dependent on vascular resistance and heart rate. Assessment of pulsatile arterial haemodynamics and time-resolved myocardial wall stress provide critical incremental physiological information and should be more widely utilised. Pulsatile arterial load represents a promising therapeutic target in HFpEF. Here, we review various approaches to assess ventricular-arterial interactions, and their pathophysiological and clinical implications in heart failure.

RESUMEN

BACKGROUND AND AIMS: The soluble receptor for advanced glycation end products (sRAGE) has been implicated in diabetic vascular complications. We have examined the association between sRAGE and cardiac markers [NT-proBNP and cardiac troponin T (cTnT)] and subclinical vascular markers in older men with and without diabetes. METHODS: We performed a cross-sectional study of 1159 men aged 71-92 years with no history of cardiovascular disease (myocardial infarction, stroke, heart failure, coronary artery bypass graft operation or angioplasty). Prevalent diabetes included men with a doctor diagnosis of diabetes, men with fasting glucose ≥7 mmol/l or HbA1c ≥ 6.5% (N = 180). Subclinical vascular measurements included carotid intima media thickness (cIMT), arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure and arterial wave reflections [central augmentation pressure (AP) and augmentation index (AIx)]. RESULTS: sRAGE was strongly and positively associated with renal dysfunction in men with and without diabetes. sRAGE was significantly and positively associated with NT-proBNP (but not cTnT) and AP and AIx in both groups of men after adjustment for CVD risk and metabolic risk markers, renal function and inflammation. However, no association was seen between sRAGE and central aortic blood pressure, cIMT or arterial stiffness as determined by PWV in either group. CONCLUSIONS: Higher plasma sRAGE was associated with increased NT-proBNP and markers of arterial wave reflections in men both with and without diabetes. Increased sRAGE may contribute to or be a marker of worsening cardiac dysfunction or HF. Further studies with cardiac imaging data are required to confirm this.

Asunto(s)

Enfermedades Cardiovasculares/sangre , Diabetes Mellitus/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Receptor para Productos Finales de Glicación Avanzada/sangre , Troponina T/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Presión Arterial , Enfermedades Asintomáticas , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Grosor Intima-Media Carotídeo , Estudios Transversales , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatología , Hemoglobina Glucada/metabolismo , Humanos , Riñón/fisiopatología , Masculino , Pronóstico , Estudios Prospectivos , Análisis de la Onda del Pulso , Factores de Riesgo , Factores Sexuales , Reino Unido , Regulación hacia Arriba , Rigidez Vascular

RESUMEN

Multiple phase III trials over the last few decades have failed to demonstrate a clear benefit of various pharmacologic interventions in heart failure with a preserved left ventricular (LV) ejection fraction (HFpEF). Therefore, a better understanding of its pathophysiology is important. An accompanying review describes key technical and physiologic aspects regarding the deep phenotyping of arterial hemodynamics in HFpEF. This review deals with the potential of this approach to enhance our clinical, translational, and therapeutic approach to HFpEF. Specifically, the role of arterial hemodynamics is discussed in relation to (1) the pathophysiology of left ventricular diastolic dysfunction, remodeling, and fibrosis, (2) impaired oxygen delivery to peripheral skeletal muscle, which affects peripheral oxygen extraction, (3) the frequent presence of comorbidities, such as renal failure and dementia in this population, and (4) the potential to enhance precision medicine approaches. A therapeutic approach to target arterial hemodynamic abnormalities that are prevalent in this population (particularly, with inorganic nitrate/nitrite) is also discussed.

Asunto(s)

Arterias/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Volumen Sistólico , Animales , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Modelos Cardiovasculares , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico

RESUMEN

A better understanding of the pathophysiology of heart failure with a preserved left ventricular ejection fraction (HFpEF) is important. Detailed phenotyping of pulsatile hemodynamics has provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, microvascular disease, and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance, the cardinal feature of HFpEF. Furthermore, arterial pulsatile hemodynamic mechanisms likely contribute to the frequent presence of comorbidities, such as renal failure and dementia, in this population. Our therapeutic approach to HFpEF can be enhanced by clinical phenotyping tools with the potential to "segment" this population into relevant pathophysiologic categories or to identify individuals exhibiting prominent specific abnormalities that can be targeted by pharmacologic interventions. This review describes relevant technical and physiologic aspects regarding the deep phenotyping of arterial hemodynamics in HFpEF. In an accompanying review, the potential of this approach to enhance our clinical and therapeutic approach to HFpEF is discussed.

Asunto(s)

Arterias/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Volumen Sistólico , Animales , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Modelos Cardiovasculares , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico

RESUMEN

BACKGROUND: Left ventricular (LV) structure and function are predictors of cardiovascular (CV) morbidity and mortality and are related to resting peripheral haemodynamic load in older adults. The central haemodynamic response to exercise may reveal associations with LV structure and function not detected by traditional peripheral (brachial) measures in a younger population. PURPOSE: To examine correlations between acute exercise-induced changes in central artery stiffness and wave reflections and measures of resting LV structure and function. METHODS: Sixteen healthy men (age 26 ± 6 year; BMI 25·3 ± 2·7 kg m-2 ) had measures of central haemodynamic load measured before/after a 30-s Wingate anaerobic test (WAT). Common carotid artery stiffness and reflected wave intensity were assessed via wave intensity analysis as a regional pulse wave velocity (PWV) and negative area (NA), respectively. Resting LV structure (LV mass) and function [midwall fractional shortening (mFS)] were assessed using M-mode echocardiography in the parasternal short-axis view. RESULTS: There was a significant association between mFS and WAT-mediated change in carotid systolic BP (r = -0·57, P = 0·011), logNA (r = -0·58, P = 0·009) and PWV (r = -0·44, P = 0·045). There were no significant associations between resting mFS and changes in brachial systolic BP (r = -0·26, P>0·05). There were no associations between resting LV mass and changes in any haemodynamic variable (P>0·05). CONCLUSION: Exercise-induced increases in central haemodynamic load reveal associations with lower resting LV function in young healthy men undetected by traditional peripheral haemodynamics.

Asunto(s)

Arteria Carótida Común/fisiología , Ejercicio Físico/fisiología , Ventrículos Cardíacos/anatomía & histología , Hemodinámica , Descanso/fisiología , Rigidez Vascular , Función Ventricular Izquierda , Adaptación Fisiológica , Adulto , Arteria Braquial/fisiología , Arteria Carótida Común/diagnóstico por imagen , Ecocardiografía , Prueba de Esfuerzo , Voluntarios Sanos , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Análisis de la Onda del Pulso , Ultrasonografía Doppler , Adulto Joven