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Accurate assessment of the left ventricular (LV) systolic function is indispensable in the clinic. However, estimation of a precise index of cardiac contractility, i.e., the end-systolic elastance (Ees), is invasive and cannot be established as clinical routine. The aim of this work was to present and validate a methodology that allows for the estimation of Ees from simple and readily available noninvasive measurements. The method is based on a validated model of the cardiovascular system and noninvasive data from arm-cuff pressure and routine echocardiography to render the model patient-specific. Briefly, the algorithm first uses the measured aortic flow as model input and optimizes the properties of the arterial system model to achieve correct prediction of the patient's peripheral pressure. In a second step, the personalized arterial system is coupled with the cardiac model (time-varying elastance model) and the LV systolic properties, including Ees, are tuned to predict accurately the aortic flow waveform. The algorithm was validated against invasive measurements of Ees (multiple pressure-volume loop analysis) taken from n = 10 patients with heart failure with preserved ejection fraction and n = 9 patients without heart failure. Invasive measurements of Ees (median = 2.4 mmHg/mL, range = [1.0, 5.0] mmHg/mL) agreed well with method predictions (normalized root mean square error = 9%, ρ = 0.89, bias = -0.1 mmHg/mL, and limits of agreement = [-0.9, 0.6] mmHg/mL). This is a promising first step toward the development of a valuable tool that can be used by clinicians to assess systolic performance of the LV in the critically ill.NEW & NOTEWORTHY In this study, we present a novel model-based method to estimate the left ventricular (LV) end-systolic elastance (Ees) according to measurement of the patient's arm-cuff pressure and a routine echocardiography examination. The proposed method was validated in vivo against invasive multiple-loop measurements of Ees, achieving high correlation and low bias. This tool could be most valuable for clinicians to assess the cardiovascular health of critically ill patients.
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Algoritmos , Determinação da Pressão Arterial , Ecocardiografia , Insuficiência Cardíaca/diagnóstico , Hemodinâmica , Modelos Cardiovasculares , Função Ventricular Esquerda , Idoso , Determinação da Pressão Arterial/instrumentação , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Esfigmomanômetros , SístoleRESUMO
Diastolic dysfunction (DD) is a major component of heart failure with preserved ejection fraction (HFpEF). Accordingly, a profound understanding of the underlying biomechanical mechanisms involved in DD is needed to elucidate all aspects of HFpEF. In this study, we have developed a computational model of DD by leveraging the power of an advanced one-dimensional arterial network coupled to a four-chambered zero-dimensional cardiac model. The two main pathologies investigated were linked to the active relaxation of the myocardium and the passive stiffness of the left ventricular wall. These pathologies were quantified through two parameters for the biphasic delay of active relaxation, which simulate the early and late-phase relaxation delay, and one parameter for passive stiffness, which simulates the increased nonlinear stiffness of the ventricular wall. A parameter sensitivity analysis was conducted on each of the three parameters to investigate their effect in isolation. The three parameters were then concurrently adjusted to produce the three main phenotypes of DD. It was found that the impaired relaxation phenotype can be replicated by mainly manipulating the active relaxation, the pseudo-normal phenotype was replicated by manipulating both the active relaxation and passive stiffness, and, finally, the restricted phenotype was replicated by mainly changing the passive stiffness. This article presents a simple model producing a holistic and comprehensive replication of the main DD phenotypes and presents novel biomechanical insights on how key parameters defining the relaxation and stiffness properties of the myocardium affect the development and manifestation of DD.NEW & NOTEWORTHY This study uses a complete and validated computational model of the cardiovascular system to simulate the two main pathologies involved in diastolic dysfunction (DD), i.e., abnormal active relaxation and increased ventricular diastolic stiffness. The three phenotypes of DD were successfully replicated according to literature data. We elucidate the biomechanical effect of the relaxation pathologies involved and how these pathologies interact to create the various phenotypes of DD.
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Simulação por Computador , Insuficiência Cardíaca/fisiopatologia , Modelos Cardiovasculares , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Fenômenos Biomecânicos , Diástole , Humanos , Fenótipo , Volume Sistólico , Pressão VentricularRESUMO
Transcatheter aortic valve replacement (TAVR) is increasingly used to treat severe aortic stenosis (AS) patients. However, little is known regarding the direct effect of TAVR on the ventricular-aortic interaction. In the present study, we aimed to investigate changes in central hemodynamics after successful TAVR. We retrospectively examined 33 cases of severe AS patients (84 ± 6 yr) who underwent TAVR. Invasive measurements of left ventricular and aortic pressures as well as echocardiographic aortic flow were acquired before and after TAVR (maximum within 5 days). We examined alterations in key features of central pressure and flow waveforms, including the aortic augmentation index (AIx), and performed wave separation analysis. Arterial parameters were determined via parameter-fitting on a two-element Windkessel model. Resolution of AS resulted in direct increase in the aortic systolic pressure and maximal aortic flow (131 ± 22 vs. 157 ± 25 mmHg and 237 ± 49 vs. 302 ± 69 mL/s, P < 0.001 for all), whereas the ejection duration decreased (P < 0.001). We noted a significant decrease in the AIx (from 42 ± 12 to 19 ± 11%, P < 0.001). Of note, the arterial properties remained unchanged. There was a comparable increase in both forward (61 ± 20 vs. 77 ± 20 mmHg, P < 0.001) and backward (35 ± 14 vs. 42 ± 10 mmHg, P = 0.013) pressure wave amplitudes, while their ratio, i.e., the reflection coefficient, was preserved. Our results highlight the impact of TAVR on the ventricular-aortic interaction by affecting the amplitude, shape, and related attributes of the aortic pressure and flow pulse and challenge the interpretation of AIx as a solely vascular measure in AS patients.NEW & NOTEWORTHY Transcatheter aortic valve replacement (TAVR) is linked with an immediate increase in aortic systolic blood pressure and maximal flow, as well as steeper aortic pressure and flow wave upstrokes. After TAVR, the forward wave pumped by the heart is enhanced. Although the arterial properties remain unchanged, the central augmentation index (AIx) is markedly decreased after TAVR. This challenges the interpretation of AIx as a solely vascular measure in patients with aortic valve stenosis.
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Aorta/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Pressão Arterial , Substituição da Valva Aórtica Transcateter , Função Ventricular Esquerda , Pressão Ventricular , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Modelos Cardiovasculares , Análise de Onda de Pulso , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Secondary mitral regurgitation is a frequent valvulopathy due to left ventricle remodeling. Although, its poor prognostic has been established, surgical interventions have shown no substantial benefits in terms of mortality benefit. MitraClip represents a transcatheter alternative. Two randomized trials - MITRA-FR and COAPT comparing the clipping versus optimal medical therapy- have confirmed the feasibility of this intervention in patients with secondary mitral regurgitation. MITRA-FR did not show any significant benefit for the MitraClip group with respect to the composite endpoint (all-cause mortality and rehospitalization for heart failure) at 12 months. On the other hand, COAPT showed a clear superiority of MitraClip in terms of mortality and rehospitalization rates, compared to the conservative treatment alone at 24 months.
L'insuffisance mitrale secondaire est une pathologie fréquente dont la prise en charge médicale est primordiale. L'approche chirurgicale n'a pas montré de bénéfice significatif en termes de réduction de la mortalité. Récemment, les procédures d'implantation de clips mitraux ont été analysées au cours de deux études randomisées (MITRA-FR et COAPT) qui comparent le clip à un traitement médicamenteux optimal. MITRA-FR n'a pas montré de bénéfice du clip par rapport au traitement médicamenteux pour le critère de jugement primaire (mortalité de toute cause et réhospitalisation pour insuffisance cardiaque) à 12 mois. A l'opposé, l'étude COAPT a montré un clair bénéfice du MitraClip par rapport au traitement conservateur en termes de mortalité globale et réhospitalisation pour insuffisance cardiaque à 24 mois.
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Insuficiência Cardíaca , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Insuficiência Cardíaca/etiologia , Humanos , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: Achieving optimal exposure of the mitral valve during surgical intervention poses a significant challenge. This study aimed to compare perioperative and postoperative outcomes associated with 3 left atriotomy techniques in mitral valve surgery-the conventional direct, transseptal, and superior septal approaches-and assess differences during the surgical procedure and the postoperative period. METHODS: Inclusion criteria were patients undergoing mitral valve surgery from January 2010 to December 2020, categorized into 3 cohorts: group 1 (conventional direct; n = 115), group 2 (transseptal; n = 33), and group 3 (superior septal; n = 59). To bolster sample size, the study included patients undergoing mitral valve surgery independently or in conjunction with other procedures (eg, coronary artery bypass grafting, aortictricuspid surgery, or maze procedure). RESULTS: No substantial variance was observed in the etiology of mitral valve disease across groups, except for a higher incidence of endocarditis in group 3 (P = .01). Group 1 exhibited a higher frequency of elective surgeries and isolated mitral valve procedures (P = .008), along with reduced aortic clamping and cardiopulmonary bypass durations (P = .002). Conversely, group 3 patients represented a greater proportion of emergency procedures (P = .01) and prolonged intensive care unit and hospital stays (P = .001). No significant disparities were detected in terms of permanent pacemaker implantation, postoperative complications, or mortality among the groups. CONCLUSION: Mitral valve operations that employed these 3 atriotomy techniques demonstrated a safe profile. The conventional direct approach notably reduced aortic clamping and cardiopulmonary bypass durations. The superior septal method was primarily employed for acute pathologies, with no significant escalation in postoperative arrhythmias or permanent pacemaker implantation, although these patients had prolonged intensive care unit and hospital stays. These outcomes may be linked to the underlying pathology and nature of the surgical intervention rather than the incision method itself.
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Procedimentos Cirúrgicos Cardíacos , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Humanos , Doenças das Valvas Cardíacas/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Decreased endothelial Nitric oxide (NO) bioavailability is one of the earliest events of endothelial dysfunction. Assessment of microvascular blood flow using a Laser Doppler Imager during local noninvasive administration of L-N-Arginine-Methyl-Ester (L-NAME) by skin iontophoresis may help discriminate the relative contributions of NO and non-NO pathways during a skin thermal hyperemic test. METHODS: In healthy nonsmokers, the effects of thermal vasodilation and sodium nitroprusside-mediated vasodilation were tested on skin pretreated with 0.9% saline solution, 2% L-NAME iontophoresis (n = 12), or intradermal injection of 25 nmol L-NAME (n = 10). The effects of L-NAME iontophoresis were also measured in a group of smokers (n = 10). RESULTS: L-NAME iontophoresis and intradermal injection of L-NAME decreased the skin response to local heating to a similar degree (-41% ± 4% vs. -44% ± 6%). L-NAME iontophoresis site-to-site and day-to-day coefficients of correlation were 0.83 and 0.76, respectively (P < 0.01). The site-to-site and day-to-day coefficients of correlation of L-NAME injection were lower than those of iontophoresis at 0.66 (P < 0.05) and 0.12, respectively (P = not significant). Sodium nitroprusside-induced skin hyperemia was not affected by L-NAME administration. L-NAME iontophoresis-mediated inhibition of skin thermal hyperemia was greater in smokers than in nonsmokers (P < 0.05). CONCLUSIONS: Laser Doppler Imager assessment of skin thermal hyperemia after L-NAME iontophoresis provides a reproducible and selective bedside method of qualitatively analyzing the contribution of the NO pathway to microvascular vasomotor function.
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Inibidores Enzimáticos/administração & dosagem , Hiperemia/fisiopatologia , Hipertermia Induzida , Iontoforese , NG-Nitroarginina Metil Éster/administração & dosagem , Pele/irrigação sanguínea , Vasodilatação/fisiologia , Adulto , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Estudos de Viabilidade , Humanos , Injeções Intradérmicas , Fluxometria por Laser-Doppler , Masculino , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/administração & dosagem , Nitroprussiato/administração & dosagem , Reprodutibilidade dos Testes , Transdução de Sinais , Fumar/efeitos adversos , Fumar/fisiopatologia , Vasodilatação/efeitos dos fármacos , Adulto JovemRESUMO
In the last few years, technological advances in MR imaging, PET detectors, and attenuation correction algorithms have allowed the creation of truly integrated PET/MR imaging systems, for both clinical and research applications. These machines allow a comprehensive investigation of cardiovascular diseases, by offering a wide variety of detailed anatomical and functional data in combination. Despite significant pathophysiologic mechanisms being clarified by this new data, its clinical relevance and prognostic significance have not been demonstrated yet.
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Relevância Clínica , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de PósitronsRESUMO
The transaortic valvular pressure gradient (TPG) plays a central role in decision-making for patients suffering from severe aortic stenosis. However, the flow-dependence nature of the TPG makes the diagnosis of aortic stenosis challenging since the markers of cardiac performance and afterload present high physiological interdependence and thus, isolated effects cannot be measured directly in vivo. We used a validated 1D mathematical model of the cardiovascular system, coupled with a model of aortic stenosis, to assess and quantify the independent effect of the main left ventricular performance parameters (end-systolic (Ees) and end-diastolic (Eed) elastance) and principal afterload indices (total vascular resistance (TVR) and total arterial compliance (TAC)) on the TPG for different levels of aortic stenosis. In patients with critical aortic stenosis (aortic valve area (AVA) ≤ 0.6 cm2), a 10% increase of Eed from the baseline value was associated with the most important effect on the TPG (-5.6 ± 0.5 mmHg, p < 0.001), followed by a similar increase of Ees (3.4 ± 0.1 mmHg, p < 0.001), in TAC (1.3 ±0.2 mmHg, p < 0.001) and TVR (-0.7 ± 0.04 mmHg, p < 0.001). The interdependence of the TPG left ventricular performance and afterload indices become stronger with increased aortic stenosis severity. Disregarding their effects may lead to an underestimation of stenosis severity and a potential delay in therapeutic intervention. Therefore, a comprehensive evaluation of left ventricular function and afterload should be performed, especially in cases of diagnostic challenge, since it may offer the pathophysiological mechanism that explains the mismatch between aortic severity and the TPG.
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Introduction: Arterial wave reflection is an important component of the left ventricular afterload, affecting both pressure and flow to the aorta. The aim of the present study was to evaluate the impact of wave reflection on transvalvular pressure gradients (TPG), a key parameter for the evaluation of aortic valve stenosis (AS), as well as its prognostic significance in patients with AS undergoing a transcatheter aortic valve replacement (TAVR). Materials and Methods: The study population consisted of 351 patients with AS (mean age 84 ± 6 years, 43% males) who underwent a complete hemodynamic evaluation before the TAVR. The baseline assessment included right and left heart catheterization, transthoracic echocardiography, and a thorough evaluation of the left ventricular afterload by means of wave separation analysis. The cohort was divided into quartiles according to the transit time of the backward pressure wave (BWTT). Primary endpoint was all-cause mortality at 1 year. Results: Early arrival of the backward pressure wave was related to lower cardiac output (Q1: 3.7 ± 0.9 lt/min vs Q4: 4.4 ± 1.0 lt/min, p < 0.001) and higher aortic systolic blood pressure (Q1: 132 ± 26 mmHg vs Q4: 117 ± 26 mmHg, p < 0.001). TPG was significantly related to the BWTT, patients in the arrival group exhibiting the lowest TPG (mean TPG, Q1: 37.6 ± 12.7 mmHg vs Q4: 44.8 ± 14.7 mmHg, p = 0.005) for the same aortic valve area (AVA) (Q1: 0.58 ± 0.35 cm2 vs 0.61 ± 0.22 cm2, p = 0.303). In multivariate analysis, BWTT remained an independent determinant of mean TPG (beta 0.3, p = 0.002). Moreover, the prevalence of low-flow, low-gradient AS with preserved ejection fraction was higher in patients with early arterial reflection arrival (Q1: 33.3% vs Q4: 14.9%, p = 0.033). Finally, patients with early arrival of the reflected wave (Q1) exhibited higher all-cause mortality at 1 year after the TAVR (unadjusted HR: 2.33, 95% CI: 1.17-4.65, p = 0.016). Conclusion: Early reflected wave arrival to the aortic root is associated with poor prognosis and significant aortic hemodynamic alterations in patients undergoing a TAVR for AS. This is related to a significant decrease in TPG for a given AVA, leading to a possible underestimation of the AS severity.
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Introduction: Pulmonary hypertension (PH), traditionally defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg, is associated with poor outcomes in patients undergoing a transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Recently, a novel definition for PH has been proposed, placing the cut-off value of mean PAP at 20 mmHg, and introducing pulmonary vascular resistance as an exclusive indicator for the pre-capillary involvement. In light of the novel criteria, whether PH still preserves its prognostic significance remains unknown. Methods: The study population consisted of 380 patients with AS, who underwent a right heart catheterization before TAVR. The cohort was divided according to the presence of PH (n = 174, 45.7%) or not. Patients with PH were further divided into the following groups: (1) Pre-capillary PH ((Pre-capPH), n = 46, 12.1%); (2) Isolated post-capillary PH ((IpcPH), n = 78, 20.5%); (3) Combined pre and post-capillary PH ((CpcPH), n = 82, 21.6%). The primary endpoint was all-cause mortality at 1 year. Results: A total of 246 patients (64.7%) exhibited mean PAP > 20 mmHg. Overall, the presence of PH was associated with higher 1-year mortality rates (hazard ratio (HR) 2.8, 95% CI: 1.4−5.8, p = 0.004). Compared to patients with no PH, Pre-capPH and CpcPH (but not IpcPH) were related to higher 1-year mortality (HR 2.7, 95% CI: 1.0−7.2, p = 0.041 and HR 3.9, 95% CI: 1.8−8.5, p = 0.001, respectively). This remained significant even after the adjustment for baseline comorbidities. Conclusions: Pre-interventional PH according to the novel hemodynamic criteria, is linked with poor outcomes in patients undergoing TAVR for severe AS. However, this is mainly driven by patients with mean PAP ≥ 25 mmHg. Patients with a pre-capillary PH component as defined by increased PVR present an even worse prognosis as compared to patients with isolated post-capillary or no PH who present comparable 1-year mortality rates.
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Aortic compliance is an important determinant of cardiac afterload and a contributor to cardiovascular morbidity. In the present study, we sought to provide in silico insights into the acute as well as long-term effects of aortic compliance decrease on central hemodynamics. To that aim, we used a mathematical model of the cardiovascular system to simulate the hemodynamics (a) of a healthy young adult (baseline), (b) acutely after banding of the proximal aorta, (c) after the heart remodeled itself to match the increased afterload. The simulated pressure and flow waves were used for subsequent wave separation analysis. Aortic banding induced hypertension (SBP 106 mmHg at baseline versus 152 mmHg after banding), which was sustained after left ventricular (LV) remodeling. The main mechanism that drove hypertension was the enhancement of the forward wave, which became even more significant after LV remodeling (forward amplitude 30 mmHg at baseline versus 60 mmHg acutely after banding versus 64 mmHg after remodeling). Accordingly, the forward wave's contribution to the total pulse pressure increased throughout this process, while the reflection coefficient acutely decreased and then remained roughly constant. Finally, LV remodeling was accompanied by a decrease in augmentation index (AIx 13% acutely after banding versus -3% after remodeling) and a change of the central pressure wave phenotype from the characteristic Type A ("old") to Type C ("young") phenotype. These findings provide valuable insights into the mechanisms of hypertension and provoke us to reconsider our understanding of AIx as a solely arterial parameter.
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Left ventricular end-systolic elastance (Ees) is a major determinant of cardiac systolic function and ventricular-arterial interaction. Previous methods for the Ees estimation require the use of the echocardiographic ejection fraction (EF). However, given that EF expresses the stroke volume as a fraction of end-diastolic volume (EDV), accurate interpretation of EF is attainable only with the additional measurement of EDV. Hence, there is still need for a simple, reliable, noninvasive method to estimate Ees. This study proposes a novel artificial intelligence-based approach to estimate Ees using the information embedded in clinically relevant systolic time intervals, namely the pre-ejection period (PEP) and ejection time (ET). We developed a training/testing scheme using virtual subjects (n = 4,645) from a previously validated in-silico model. Extreme Gradient Boosting regressor was employed to model Ees using as inputs arm cuff pressure, PEP, and ET. Results showed that Ees can be predicted with high accuracy achieving a normalized RMSE equal to 9.15% (r = 0.92) for a wide range of Ees values from 1.2 to 4.5 mmHg/ml. The proposed model was found to be less sensitive to measurement errors (±10-30% of the actual value) in blood pressure, presenting low test errors for the different levels of noise (RMSE did not exceed 0.32 mmHg/ml). In contrast, a high sensitivity was reported for measurements errors in the systolic timing features. It was demonstrated that Ees can be reliably estimated from the traditional arm-pressure and echocardiographic PEP and ET. This approach constitutes a step towards the development of an easy and clinically applicable method for assessing left ventricular systolic function.
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Ventricular-arterial coupling is a major determinant of cardiovascular performance, however, there are still inherent difficulties in distinguishing ventricular from vascular effects on arterial pulse phenotypes. In the present study, we employed an extensive mathematical model of the cardiovascular system to investigate how sole changes in cardiac contractility might affect hemodynamics. We simulated two physiologically relevant cases of high and low contractility by altering the end-systolic elastance, Ees, (3 versus 1 mmHg/mL) under constant cardiac output and afterload, and subsequently performed pulse wave analysis and wave separation. The aortic forward pressure wave component was steeper for high Ees, which led to the change of the total pressure waveform from the characteristic Type A phenotype to Type C, and the decrease in augmentation index, AIx (-2.4% versus +18.1%). Additionally, the increase in Ees caused the pulse pressure amplification from the aorta to the radial artery to rise drastically (1.86 versus 1.39). Our results show that an increase in cardiac contractility alone, with no concomitant change in arterial properties, alters the shape of the forward pressure wave, which, consequently, changes central and peripheral pulse phenotypes. Indices based on the pressure waveform, like AIx, cannot be assumed to reflect only arterial properties.
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Aorta/fisiopatologia , Artérias/fisiologia , Hemodinâmica , Modelos Cardiovasculares , Modelos Teóricos , Contração Miocárdica , Função Ventricular Esquerda/fisiologia , Pressão Sanguínea , Humanos , Análise de Onda de PulsoRESUMO
The compliance of the proximal aortic wall is a major determinant of cardiac afterload. Aortic compliance is often estimated based on cross-sectional area changes over the pulse pressure, under the assumption of a negligible longitudinal stretch during the pulse. However, the proximal aorta is subjected to significant axial stretch during cardiac contraction. In the present study, we sought to evaluate the importance of axial stretch on compliance estimation by undertaking both an in silico and an in vivo approach. In the computational analysis, we developed a 3-D finite element model of the proximal aorta and investigated the discrepancy between the actual wall compliance to the value estimated after neglecting the longitudinal stretch of the aorta. A parameter sensitivity analysis was further conducted to show how increased material stiffness and increased aortic root motion might amplify the estimation errors (discrepancies between actual and estimated distensibility ranging from - 20 to - 62%). Axial and circumferential aortic deformation during ventricular contraction was also evaluated in vivo based on MR images of the aorta of 3 healthy young volunteers. The in vivo results were in good qualitative agreement with the computational analysis (underestimation errors ranging from - 26 to - 44%, with increased errors reflecting higher aortic root displacement). Both the in silico and in vivo findings suggest that neglecting the longitudinal strain during contraction might lead to severe underestimation of local aortic compliance, particularly in the case of women who tend to have higher aortic root motion or in subjects with stiff aortas.
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Aorta/fisiologia , Adolescente , Adulto , Aorta/diagnóstico por imagem , Fenômenos Biomecânicos , Complacência (Medida de Distensibilidade) , Simulação por Computador , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Modelos Cardiovasculares , Movimento (Física) , PressãoRESUMO
BACKGROUND: Transcatheter aortic valve implantation (TAVI) represents an effective therapeutic procedure, particularly in patients with severe aortic stenosis. We hypothesized that the decreased afterload induced by TAVI would improve exercise capacity by enhancing oxygen uptake in working muscles. METHODS: A standardized exercise test was performed in patients with severe aortic stenosis the day before TAVI and within 5 days thereafter. The main study endpoint was the workload achieved during a 5-minute standardized exercise test. Using electrical cardiometry and near-infrared spectroscopy, we explored and compared the changes in cardiac index (CI), as well as muscular and cerebral tissue oximetry, during the 2 exercise tests. RESULTS: Thirty patients completed the study protocol. Compared with the pre-TAVI period, patients achieved a higher median workload after TAVI (316 Joules [interquartile range {IQR}: 169-494] vs 190 Joules [IQR: 131-301], P = 0.002). Baseline CI increased from 2.5 l/min per m2 (IQR: 2.1-2.9) to 2.9 l/min per m2 (IQR: 2.5-3.2; P = 0.009), whereas CI at the end of the exercise test increased from 4.5 l/min per m2 (IQR: 3.4-5.3) to 4.7 l/min per m2 (3.4-6.4; P = 0.019). At the end of the exercise test, cerebral tissue oximetry increased from 70% (IQR: 65-72) to 74% (IQR: 66-78), and muscle tissue oximetry increased from 62% (IQR: 58-65) to 71% (65-74; P = 0.046 and P < 0.001, respectively). CONCLUSIONS: Early improvement of exercise capacity after TAVI is associated with increased CI and better oxygen utilization in the brain and skeletal muscles.
CONTEXTE: Le remplacement valvulaire aortique par cathéter (TAVI) représente une procédure thérapeutique efficace, en particulier chez les patients présentant une sténose aortique sévère. Nous avons émis l'hypothèse que la diminution de la postcharge induite par le TAVI améliorerait la capacité à l'effort en favorisant la consommation d'oxygène des muscles travaillant. MÉTHODES: Un test d'effort standardisé a été réalisé chez des patients souffrant de sténose aortique sévère la veille de l'intervention TAVI et dans les 5 jours qui ont suivi. Le principal critère d'évaluation de l'étude était la charge de travail atteinte lors d'un test d'effort standardisé de 5 minutes. En utilisant la cardiométrie électrique et la spectroscopie proche infrarouge, nous avons exploré et comparé les changements de l'index cardiaque (IC), ainsi que l'oxymétrie des tissus musculaires et cérébraux, pendant les 2 tests d'effort. RÉSULTATS: Trente patients ont terminé le protocole d'étude. Par rapport à la période pré-TAVI, les patients ont atteint une charge de travail médiane plus élevée après le TAVI (316 Joules [intervalle interquartile (IIQ) : 169-494] contre 190 Joules [IIQ : 131-301], p = 0.002). L'IC de base est passé de 2,5 l/min par m2 (IIQ : 2,1-2,9) à 2,9 l/min par m2 (IIQ : 2,5-3,2 ; p = 0.009), tandis que l'IC à la fin du test d'effort est passé de 4,5 l/min par m2 (IIQ : 3.4-5.3) à 4,7 l/min par m2 (3,4-6,4 ; p = 0,019). À la fin du test d'effort, l'oxymétrie du tissu cérébral est passée de 70 % (IIQ : 65-72) à 74 % (IIQ : 66-78), et l'oxymétrie du tissu musculaire est passée de 62 % (IIQ : 58-65) à 71 % (65-74; p = 0,046 et p < 0,001, respectivement). CONCLUSIONS: L'amélioration précoce de la capacité d'exercice après le TAVI est associée à un IC accru et à une meilleure utilisation de l'oxygène au niveau du cerveau et des muscles squelettiques.
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1. Recently, we have demonstrated that cigarette smoke exposure proportionally increases plasma nicotine levels and arterial wave reflection to the aorta. However, the exact contribution of nicotine to the smoke-induced enhancement of wave reflection and the potential underlying mechanisms have not been fully investigated. 2. The present study was a prospective study in 15 healthy male non-smokers. All received a placebo and a 2 mg nicotine tablet, according to a randomized double-blind cross-over study design. Each subject underwent repeated measurements at baseline and for 1 h after nicotine or placebo intake, using carotid-femoral pulse wave velocity (PWV) to assess arterial compliance. Concurrently, aortic pressures and the augmentation index were evaluated using applanation tonometry. 3. Plasma nicotine concentrations achieved 1 h after intake of the nicotine tablet reached comparable levels to those achieved after 1 h exposure to passive smoke (3.6 +/- 0.4 vs 3.2 +/- 0.4 ng/mL, respectively; P = 0.4). 4. Nicotine enhanced arterial wave reflection to the aorta, as assessed by the augmentation index corrected for heart rate (4.2 +/- 1.3 vs-0.7 +/- 0.8% with placebo; P = 0.001). In addition, a progressive increase in carotid-femoral PWV was noted after nicotine administration (0.3 +/- 0.1 vs-0.02 +/- 0.1 m/s with placebo; P = 0.04). This remained significant even after adjustment for changes in mean blood pressure and heart rate (P = 0.01). 5. Plasma nicotine concentrations comparable to those achieved after exposure to passive smoke enhance arterial wave reflection to the aorta. This is accompanied by an increase in carotid-femoral PWV, denoting a deterioration of arterial compliance by nicotine.
Assuntos
Aorta/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Artéria Femoral/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Nicotina/efeitos adversos , Animais , Aorta/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Artérias Carótidas/fisiopatologia , Estudos Cross-Over , Método Duplo-Cego , Elasticidade , Artéria Femoral/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Nicotina/sangue , Estudos Prospectivos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto JovemRESUMO
Blockade of the skeletal muscle Na(+)-K(+)-ATPase pump by digoxin could result in a more marked hyperkaliema during a forearm exercise, which in turn could stimulate the mechano- and metaboreceptors. In a randomized, double-blinded, placebo-controlled, and cross-over-design study, we measured mean blood pressure (MBP), heart rate (HR), ventilation (V(E)), oxygen saturation (SpO(2)), muscle sympathetic nerve activity (MSNA), venous plasma potassium and lactic acid during dynamic handgrip exercises, and local circulatory arrest in 11 healthy subjects. Digoxin enhanced MBP during exercise but not during the post-handgrip ischemia and had no effect on HR, V(E), SpO(2), and MSNA. Venous plasma potassium and lactic acid were also not affected by digoxin-induced skeletal muscle Na(+)-K(+)-ATPase blockade. We conclude that digoxin increased MBP during dynamic exercise in healthy humans, independently of changes in potassium and lactic acid. A modest direct sensitization of the muscle mechanoreceptors is unlikely and other mechanisms, independent of muscle reflexes and related to the inotropic effects of digoxin, might be implicated.
Assuntos
Digoxina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Reflexo de Estiramento/efeitos dos fármacos , Cardiotônicos/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Exercício Físico/fisiologia , Força da Mão/fisiologia , Humanos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Esquelético/fisiologia , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Placebos , Reflexo de Estiramento/fisiologia , Adulto JovemRESUMO
INTRODUCTION: We sought to identify baseline and periprocedural variables affecting hospital length of stay (LoS) in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: Data on 304 consecutive patients undergoing TAVI at a single centre between August 2008 and December 2017 were collected prospectively. All patients underwent a complete clinical, echocardiographic and laboratory evaluation including a comprehensive frailty assessment at baseline. LoS was defined as the number of in-hospital days after the TAVI procedure during the index hospitalisation until the time the patient left the hospital for home or a rehabilitation clinic. RESULTS: The mean LoS was 10.4 ± 7.1 days (median 8, interquartile range 5–12) with a significant trend towards shorter LoS over time (p <0.001). Patients discharged directly home were more likely to have shorter LoS (p = 0.007). All periprocedural complications were significantly associated with prolonged LoS (p <0.05 for all). Multivariate analysis showed an independent association between LoS and emergency admission (beta 3.24 ± 1.56, p = 0.039), baseline gait speed (beta: 0.39 ± 0.16, p = 0.018), baseline serum C-reactive protein (CRP, beta 0.14 ± 0.04, p = 0.001) and subclavian access (beta 8.27 ± 2 .9, p = 0.005). Gait speed and serum CRP remained significant determinants of LoS even after adjustment for periprocedural complications and patients’ discharge destination. CONCLUSION: Baseline gait speed and serum CRP are significant independent determinants of LoS after TAVI.
Assuntos
Tempo de Internação/estatística & dados numéricos , Próteses e Implantes , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Hospitalização , Humanos , Masculino , Alta do Paciente/estatística & dados numéricos , Estudos ProspectivosRESUMO
BACKGROUND: The peripheral chemoreflex contributes to cardiovascular regulation and represents the first line of defence against hypoxia. The effects of nicotine on chemoreflex regulation in non-smoking humans are unknown. METHOD: We conducted a prospective, randomized, crossover, and placebo-controlled study in 20 male non-smokers to test the hypothesis that nicotine increases chemoreflex sensitivity. The effects of two intakes of 2 mg nicotine tabs and placebo on sympathetic nerve activity to muscle circulation (muscle sympathetic nerve activity; MSNA), minute ventilation (Ve), blood pressure and heart rate were assessed during normoxia, moderate isocapnic hypoxia, hyperoxic hypercapnia and an isometric handgrip in 10 subjects. Maximal end-expiratory apnoeas were performed at baseline and at the end of the fifth minute of hypoxia. In a second experimental setting, we studied the ventilatory response to a more marked isocapnic hypoxia in 10 other volunteers. RESULTS: Mean MSNA and Ve were not modified by nicotine during the 5 min of normoxia or moderate hypoxia. In the presence of nicotine MSNA was related to oxygen desaturation (P < 0.01). The sympathoexcitatory effects of nicotine became especially evident when apnoeas achieved oxygen saturations less than 85% (511 +/- 44% increase in MSNA after the first intake, and 436 +/- 43% increase after the second intake versus 387 +/- 56% and 338 +/- 31% with placebo, respectively, P < 0.05). Nicotine also increased the ventilatory response compared with placebo when oxygen saturation decreased to less than 85% (P < 0.05). CONCLUSION: This is the first study to demonstrate that nicotine increases peripheral chemoreflex sensitivity to large reductions in arterial oxygen content in healthy non-smokers.
Assuntos
Células Quimiorreceptoras/efeitos dos fármacos , Estimulantes Ganglionares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipóxia/fisiopatologia , Nicotina/farmacologia , Respiração/efeitos dos fármacos , Adulto , Apneia/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Corpo Carotídeo/efeitos dos fármacos , Estudos Cross-Over , Eletrocardiografia/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Estudos ProspectivosRESUMO
1. Nicotine is a well studied pleiotropic agent which occurs naturally in tobacco smoke and has been largely accused for many of the adverse effects of smoking on the cardiovascular system, including autonomic imbalance, endothelial dysfunction and coronary blood flow dysregulation. 2. The acute sympathoexcitatory effects of smoking on the cardiovascular system are partially mediated by catecholamine release, muscle sympathetic nerve excitation and peripheral chemoreceptor sensitivity increase, consecutive to nicotinic receptor stimulation in the autonomic nervous system. 3. Recent animal data suggest that nicotine promotes the oxidative and inflammatory stress to the endothelium and induces pathological angiogenesis, leading to the progression of the atherosclerotic lesions. 4. Nicotine increases myocardial work without impairing the physiological coronary vasodilatation. Consequently, nicotine per se cannot explain the sudden reduction in coronary flow reserve after exposure to both active and passive smoking. 5. Nicotine's biological effects are characterized by a rapid onset of tolerance, which can explain why nicotine administration does not elicit acute coronary and chemoreflex side-effect in smokers.