RESUMO
This study aimed to evaluate the changes in the left ventricular (LV) myocardial work (MW) in breast cancer patients following chemotherapy by left ventricular pressure-strain loop (LVPSL).A total of 50 patients with newly breast cancer undergoing postoperative adjuvant chemotherapy containing anthracycline were selected. Echocardiography was performed before the treatment (T0), the second (T2) and fourth (T4) cycles of chemotherapy, and 3 (P3 m) and 6 (P6 m) months after the end of chemotherapy. The standard dynamic images of the required sections were collected. After off-line analysis, the routine, global myocardial strain, and global MW parameters were obtained, and the average regional MW index (RMWI) and regional MW efficiency (RMWE) at three levels of LV were calculated.Compared with those at T0 and T2, the global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and global longitudinal strain (GLS) gradually decreased and global wasted work (GWW) gradually increased at T4, P0, and P6 m. The mean RMWI and RMWE of the three levels of LV exhibited a gradually decreasing trend at T4, P0, and P6 m compared with those at T0 and T2. The GWI, GCW, GWE, mean RMWI, and RMWE (basal, medial, and apical) were negatively correlated with the GLS (r = -0.76, -0.66, -0.67, -0.76, -0.77, -0.66, -0.67, -0.59, and -0.61, respectively), whereas the GWW was positively correlated with the GLS (r = 0.55).The mean RMWI and RMWE are effective parameters to reflect the cardiotoxicity of LV, and LVPSL has certain value in the evaluation of the left ventricular myocardial work (LVMW) during anthracycline treatment and follow-up in breast cancer patients.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pressão Ventricular , Função Ventricular Esquerda , Ecocardiografia/métodos , Antraciclinas/efeitos adversos , Volume SistólicoAssuntos
Procedimentos Cirúrgicos Cardíacos , Artéria Pulmonar , Humanos , Pressão Ventricular , Coração , CateteresRESUMO
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients. OBJECTIVES: The authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH. METHODS: A total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed. RESULTS: LVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival. CONCLUSIONS: Elevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.
Assuntos
Fibrilação Atrial , Hipertensão Pulmonar , Hipertensão , Insuficiência da Valva Mitral , Estenose da Valva Mitral , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Função Ventricular Esquerda , Pressão Propulsora Pulmonar , Pressão VentricularRESUMO
BACKGROUND: The lack of reliable echocardiographic techniques to assess diastolic function in children is a major clinical limitation. Our aim was to develop and validate the intraventricular pressure difference (IVPD) calculation using blood speckle-tracking (BST) and investigate the method's potential role in the assessment of diastolic function in children. METHODS: Blood speckle-tracking allows two-dimensional angle-independent blood flow velocity estimation. Blood speckle-tracking images of left ventricular (LV) inflow from the apical 4-chamber view in 138 controls, 10 patients with dilated cardiomyopathies (DCMs), and 21 patients with hypertrophic cardiomyopathies (HCMs) <18 years of age were analyzed to study LV IVPD during early diastole. Reproducibility of the IVPD analysis was assessed, IVPD estimates from BST and color M mode were compared, and the validity of the BST-based IVPD calculations was tested in a computer flow model. RESULTS: Mean IVPD was significantly higher in controls (-2.28 ± 0.62 mm Hg) compared with in DCM (-1.21 ± 0.39 mm Hg, P < .001) and HCM (-1.57 ± 0.47 mm Hg, P < .001) patients. Feasibility was 88.3% in controls, 80% in DCM patients, and 90.4% in HCM patients. The peak relative negative pressure occurred earlier at the apex than at the base and preceded the peak E-wave LV filling velocity, indicating that it represents diastolic suction. Intraclass correlation coefficients for intra- and interobserver variability were 0.908 and 0.702, respectively. There was a nonsignificant mean difference of 0.15 mm Hg between IVPD from BST and color M mode. Estimation from two-dimensional velocities revealed a difference in peak IVPD of 0.12 mm Hg (6.6%) when simulated in a three-dimensional fluid mechanics model. CONCLUSIONS: Intraventricular pressure difference calculation from BST is highly feasible and provides information on diastolic suction and early filling in children with heart disease. Intraventricular pressure difference was significantly reduced in children with DCM and HCM compared with controls, indicating reduced early diastolic suction in these patient groups.
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Cardiomiopatia Dilatada , Cardiomiopatia Hipertrófica , Humanos , Criança , Pressão Ventricular/fisiologia , Volume Sistólico/fisiologia , Reprodutibilidade dos Testes , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Diástole/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
This study reports a new methodology for right heart imaging by ultrasound in mice under right ventricular (RV) pressure overload. Pulmonary artery constriction (PAC) or sham surgeries were performed on C57BL/6 male mice at 8 wk of age. Ultrasound imaging was conducted at 2, 4, and 8 wk postsurgery using both classical and advanced ultrasound imaging modalities including electrocardiogram (ECG)-based kilohertz visualization, anatomical M-mode, and strain imaging. Based on pulsed Doppler, the PAC group demonstrated dramatically enhanced pressure gradient in the main pulmonary artery (MPA) as compared with the sham group. By the application of advanced imaging modalities in novel short-axis views of the ventricles, the PAC group demonstrated increased thickness of RV free wall, enlarged RV chamber, and reduced RV fractional shortening compared with the sham group. The PAC group also showed prolonged RV contraction, asynchronous interplay between RV and left ventricle (LV), and passive leftward motion of the interventricular septum (IVS) at early diastole. Consequently, the PAC group exhibited prolongation of LV isovolumic relaxation time, without change in LV wall thickness or systolic function. Significant correlations were found between the maximal pressure gradient in MPA measured by Doppler and the RV systolic pressure by catheterization, as well as the morphological and functional parameters of RV by ultrasound.NEW & NOTEWORTHY The established protocol overcomes the challenges in right heart imaging in mice, thoroughly elucidating the changes of RV, the dynamics of IVS, and the impact on LV and provides new insights into the pathophysiological mechanism of RV remodeling.
Assuntos
Disfunção Ventricular Direita , Remodelação Ventricular , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Coração , Ventrículos do Coração/diagnóstico por imagem , Ultrassonografia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia , Pressão Ventricular/fisiologia , Função Ventricular DireitaRESUMO
Plasminogen activator inhibitor-1 (PAI-1) is a specific and rapid-acting inhibitor of endogenous plasminogen activators (uPA and tPA). The global PAI-1 knockout mice (PAI-1KO) develop age-dependent cardiac-selective fibrosis, and young global PAI-1KO mice exhibit augmented susceptibility to developing cardiac fibrosis in response to hypertension. Here, we tested the hypothesis that cardiomyocyte PAI-1 is necessary to provide cardioprotective effects in a left ventricular pressure overload-induced murine model of cardiac hypertrophy and fibrosis using cardiomyocyte-specific PAI-1 knockout (cmPAI-1KO) mice. The results revealed that cmPAI-1KO mice display significantly worse cardiac fibrosis than controls. To investigate the molecular mechanisms responsible for these effects, genome-wide cardiac transcriptome analysis was performed. Loss of cardiomyocyte PAI-1 led to differential expression of 978 genes compared to controls in response to left ventricular pressure overload. Pathway enrichment analysis identified the inflammatory response, cell substrate adhesion, regulation of cytokine production, leukocyte migration, extracellular matrix organization, and cytokine-mediated signaling pathways as being significantly upregulated in cmPAI-1KO hearts. Conversely, specific epigenetic repressors, cation transmembrane transport, muscle system processes, and nitric oxide signaling were significantly downregulated in cmPAI-1KO hearts compared to control hearts in response to left ventricular pressure overload. Collectively, the present study provides strong evidence of the impact of cardiomyocyte PAI-1 in regulation of the transcriptome network involved in the cardiac stress response. In response to stress, the deregulatory impact of cardiomyocyte PAI-1 loss on the cardiac transcriptome may be the underlying cause of cardiac-selective accelerated fibrogenesis in global PAI-1-deficient mice.
Assuntos
Cardiomiopatias , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Miocárdio/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Transcriptoma , Pressão Ventricular , Cardiomiopatias/patologia , Fibrose , Citocinas/metabolismo , Camundongos Knockout , Remodelação Ventricular , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. This study aimed to evaluate the change in RV pressure waveform in patients receiving a combination of inhaled epoprostenol and inhaled milrinone (iE&iM) before cardiopulmonary bypass (CPB) and to assess the safety of this approach with a matched case-control group. METHODS: A prospective single-centre cohort study of adult patients undergoing cardiac surgery administered iE&iM through an ultrasonic mesh nebulizer. RV pressure waveform monitoring was obtained by continuously transducing the RV port of the pulmonary artery (PA) catheter. RESULTS: The final analysis included 26 patients receiving iE&iM. There was a significant drop in mean PA pressure (MPAP) (-4.8 ± 8.7, P = 0.010), systolic PA pressure (SPAP) (-8.2 ± 12.8, P = 0.003), RV end-diastolic pressure (RVEDP) (-2.1 ± 2.8, P < 0.001) and RV diastolic pressure gradient (RVDPG) (-1.7 ± 1.4, P < 0.001) after 17 ± 9 minutes of iE&iM administration. Patients also had a significant increase in RV outflow tract (RVOT) gradient (3.7 ± 4.7, P < 0.001), RV maximal rate of pressure rise during early systole (dP/dt max) (68.3 ± 144.7, P = 0.024), and left ventricular (LV) dP/dt max (66.4 ± 90.1, P < 0.001). Change in RVOT gradient was only observed in those with a positive pulmonary vasodilator response to treatment. Treatment with iE&iM did not present adverse effects when compared with a matched case-control group. CONCLUSIONS: Coadministration of iE&iM in cardiac surgery patients presenting with PH or signs of RV dysfunction is a safe and effective treatment approach in improving RV function. Appearance of a transient increase in RVOT gradient after iE&iM could be useful to predict response to treatment.
Assuntos
Hipertensão Pulmonar , Disfunção Ventricular Direita , Adulto , Humanos , Milrinona , Epoprostenol , Pressão Ventricular , Estudos de Coortes , Estudos Prospectivos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Função Ventricular Direita , Disfunção Ventricular Direita/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVE: The left ventricular pressure waveform is indispensable for the construction of the pressure strain loop when investigating coronary artery disease (CAD) patients. In previous studies by others, exclusion of CAD patients has not allowed a reliable estimation of the left ventricular pressure waveform from the pressure strain loop of these patients. To remedy this, we propose a patient-specific noninvasive method for the estimation of left ventricular pressure. METHODS: A simplified systemic circulation model consisting primarily of a single fiber model and a 1D simulation of the arterial tree was used. Sensitivity analysis based on the Morris method was performed to select a subset of the important parameters. Following this, the important parameter subset and the set of all the parameters were identified in the model using the pressure waveform of a peripheral artery as input, in a two-step process. In addition, the left ventricular pressure waveform was estimated using the set of all parameters. RESULTS: Reducing the size of the parameter subset significantly decreases the computational cost of parameter optimization in the first step and greatly simplifies the identification of the full parameter set in the second step. Comparison with the reference left ventricular pressure waveform from CAD patients, showed that the proposed method provides a good estimate of the reference left ventricular pressure waveform. The correlation coefficients between the estimated and reference were r = 0.907, r = 0.904 andâ r = 0.780 for systolic blood pressure, pulse pressure and mean blood pressure, respectively. CONCLUSIONS: This work may provide a convenient surrogate for the estimation of the left ventricular pressure waveform.
Assuntos
Pressão Ventricular , Humanos , Pressão Sanguínea/fisiologia , Simulação por ComputadorRESUMO
BACKGROUND: Phase space is a mechanical systems approach and large-scale data representation of an object in 3-dimensional space. Whether such techniques can be applied to predict left ventricular pressures non-invasively and at the point-of-care is unknown. OBJECTIVE: This study prospectively validated a phase space machine-learned approach based on a novel electro-mechanical pulse wave method of data collection through orthogonal voltage gradient (OVG) and photoplethysmography (PPG) for the prediction of elevated left ventricular end diastolic pressure (LVEDP). METHODS: Consecutive outpatients across 15 US-based healthcare centers with symptoms suggestive of coronary artery disease were enrolled at the time of elective cardiac catheterization and underwent OVG and PPG data acquisition immediately prior to angiography with signals paired with LVEDP (IDENTIFY; NCT #03864081). The primary objective was to validate a ML algorithm for prediction of elevated LVEDP using a definition of ≥25 mmHg (study cohort) and normal LVEDP ≤ 12 mmHg (control cohort), using AUC as the measure of diagnostic accuracy. Secondary objectives included performance of the ML predictor in a propensity matched cohort (age and gender) and performance for an elevated LVEDP across a spectrum of comparative LVEDP (<12 through 24 at 1 mmHg increments). Features were extracted from the OVG and PPG datasets and were analyzed using machine-learning approaches. RESULTS: The study cohort consisted of 684 subjects stratified into three LVEDP categories, ≤12 mmHg (N = 258), LVEDP 13-24 mmHg (N = 347), and LVEDP ≥25 mmHg (N = 79). Testing of the ML predictor demonstrated an AUC of 0.81 (95% CI 0.76-0.86) for the prediction of an elevated LVEDP with a sensitivity of 82% and specificity of 68%, respectively. Among a propensity matched cohort (N = 79) the ML predictor demonstrated a similar result AUC 0.79 (95% CI: 0.72-0.8). Using a constant definition of elevated LVEDP and varying the lower threshold across LVEDP the ML predictor demonstrated and AUC ranging from 0.79-0.82. CONCLUSION: The phase space ML analysis provides a robust prediction for an elevated LVEDP at the point-of-care. These data suggest a potential role for an OVG and PPG derived electro-mechanical pulse wave strategy to determine if LVEDP is elevated in patients with symptoms suggestive of cardiac disease.
Assuntos
Disfunção Ventricular Esquerda , Humanos , Disfunção Ventricular Esquerda/diagnóstico , Pressão Sanguínea , Sistemas Automatizados de Assistência Junto ao Leito , Análise de Onda de Pulso , Aprendizado de Máquina , Função Ventricular Esquerda , Pressão Ventricular , Volume SistólicoRESUMO
Acute right ventricular pressure overload (RVPO) occurs following congenital heart surgery and often results in low cardiac output syndrome. We tested the hypothesis that the RV exhibits limited ability to modify substrate utilization in response to increasing energy requirements during acute RVPO after cardiopulmonary bypass (CPB). We assessed the RV fractional contributions (Fc) of substrates to the citric acid cycle in juvenile pigs exposed to acute RVPO by pulmonary artery banding (PAB) and CPB. Sixteen Yorkshire male pigs (median 38 days old, 12.2 kg of body weight) were randomized to SHAM (Ctrl, n = 5), 2-h CPB (CPB, n = 5) or CPB with PAB (PAB-CPB, n = 6). Carbon-13 (13 C)-labeled lactate, medium-chain, and mixed long-chain fatty acids (MCFA and LCFAs) were infused as metabolic tracers for energy substrates. After weaning from CPB, RV systolic pressure (RVSP) doubled baseline in PAB-CPB while piglets in CPB group maintained normal RVSP. Fc-LCFAs decreased significantly in order PAB-CPB > CPB > Ctrl groups by 13 C-NMR. Fc-lactate and Fc-MCFA were similar among the three groups. Intragroup analysis for PAB-CPB showed that the limited Fc-LCFAs appeared prominently in piglets exposed to high RVSP-to-left ventricular systolic pressure ratio and high RV rate-pressure product, an indicator of myocardial oxygen demand. Acute RVPO after CPB strongly inhibits LCFA oxidation without compensation by lactate oxidation, resulting in energy deficiency as determined by lower (phosphocreatine)/(adenosine triphosphate) in PAB-CPB. Adequate energy supply but also metabolic interventions may be required to circumvent these RV energy metabolic abnormalities during RVPO after CPB.
Assuntos
Disfunção Ventricular Direita , Suínos , Animais , Masculino , Pressão Ventricular/fisiologia , Desmame , Ponte Cardiopulmonar/efeitos adversos , Metabolismo Energético , LactatosRESUMO
Left ventricular end-diastolic pressure (LVEDP) is an important hemodynamic marker of left ventricular performance and affects coronary perfusion. We evaluated the association of LVEDP with patient outcomes after elective or urgent percutaneous coronary intervention (PCI). We included n = 49,600 patients undergoing elective or urgent PCI. Patients were divided according to LVEDP tertile for descriptive analysis. The primary end point was in-hospital mortality. A recursive partitioning tree model for mortality was built to guide decision-making in patients with high LVEDP undergoing nonemergent PCI. Overall, n = 18,099 patients had an LVEDP <13 mm Hg, n = 15,416 had an LVEDP 13 to 18 mm Hg, and n = 16,085 had an LVEDP >18 mm Hg. Patients in the high LVEDP tertile had a worse clinical and angiographic/procedural profile and experienced a higher incidence of in-hospital post-PCI adverse outcomes, including death (LVEDP <13 mm Hg 0.3% vs LVEDP 13 to 18 mm Hg 0.4% vs LVEDP >18 mm Hg 0.8%, p <0.001). An elevated LVEDP was an independent predictor of adverse outcomes including mortality. An LVEDP ≥26 mm Hg was identified as a marker of high mortality (1.5%) in patients who underwent elective PCI, with rates varying from 0.5% to 10.4%, based upon a clinical profile defined by hemoglobin, systolic blood pressure, renal and left ventricular function, and atrial fibrillation. In conclusion, an elevated LVEDP is observed in 1/3 of the patients who underwent elective or urgent PCI and is associated with higher rates of in-hospital adverse outcomes, including death. Patients with an LVEDP ≥26 mm Hg who underwent elective PCI had markedly higher mortality rates, suggesting that such patients may warrant further optimization before PCI.
Assuntos
Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Pressão Sanguínea , Fatores de Risco , Função Ventricular Esquerda/fisiologia , Ventrículos do Coração , Pressão VentricularRESUMO
A novel method to derive pressure-volume (PV) loops noninvasively from cardiac magnetic resonance images has recently been developed. The aim of this study was to evaluate inter- and intraobserver variability of hemodynamic parameters obtained from noninvasive PV loops in healthy controls, subclinical diastolic dysfunction (SDD), and patients with heart failure with preserved ejection fraction, mildly reduced ejection fraction, and reduced ejection fraction. We included 75 subjects, of whom 15 were healthy controls, 15 subjects with SDD (defined as fulfilling 1 to 2 echocardiographic criteria for diastolic dysfunction), and 15 patients with preserved ejection fraction, 15 with mildly reduced ejection fraction, and 15 with reduced ejection fraction. PV loops were computed using time-resolved left ventricular volumes from cardiac magnetic resonance images and a brachial blood pressure. Inter- and intraobserver variability and intergroup differences of PV loop-derived hemodynamic parameters were assessed. Bias was low and limits of agreement were narrow for all hemodynamic parameters in the inter- and intraobserver comparisons. Interobserver difference for stroke work was 2 ± 9%, potential energy was 4 ± 11%, and maximal ventricular elastance was -4 ± 7%. Intraobserver for stroke work was -1 ± 7%, potential energy was 3 ± 4%, and maximal ventricular elastance was 1 ± 5%. In conclusion, this study presents a fully noninvasive left ventricular PV loop analysis across healthy controls, subjects with SDD, and patients with heart failure with preserved or impaired systolic function. In conclusion, the method for PV loop computation from clinical-standard manual left ventricular segmentation was rapid and robust, bridging the gap between clinical and research settings.
Assuntos
Insuficiência Cardíaca , Acidente Vascular Cerebral , Disfunção Ventricular Esquerda , Humanos , Pressão Ventricular , Variações Dependentes do Observador , Volume Sistólico , Insuficiência Cardíaca/diagnóstico por imagem , Função Ventricular Esquerda , Disfunção Ventricular Esquerda/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagemRESUMO
We used transverse aortic constriction (TAC) in mice to test the hypothesis that urocortin 2 (Ucn2) gene transfer would increase left ventricular (LV) systolic and diastolic function in the pressure-stressed LV. Three groups were studied: (1) control mice (no TAC); (2) mice that received saline 6 weeks after TAC; and (3) mice that received Ucn2 gene transfer 6 weeks after TAC, using adeno-associated virus 8 encoding murine Ucn2 (AAV8.mUcn2; 2 × 1013 genome copies (gc)/kg, i.v. per mouse). Echocardiography was performed 6 and 12 weeks after TAC. In terminal studies 12 weeks after TAC, rates of LV pressure development and decay and Tau were measured, and LV cardiac myocytes (CMs) were isolated and cytosolic Ca2+ transients and sarcomere shortening rates recorded. Reverse transcription polymerase chain reaction and immunoblotting were used to measure key proteins in LV samples. A CM cell line (HL-1) was used to explore mechanisms. Concentric LV hypertrophy was evident on echocardiography 6 weeks after TAC. Twelve weeks after TAC, LV ejection fraction (EF) was higher in mice that received Ucn2 gene transfer (TAC-saline: 65% ± 3%; TAC-Ucn2: 75% ± 2%; p = 0.01), as was LV peak +dP/dt (1.9-fold increase; p = 0.001) and LV peak -dP/dt (1.7-fold increase; p = 0.017). Tau was more rapid (23% reduction, p = 0.02), indicating improved diastolic function. The peak rates of sarcomere shortening (p = 0.002) and lengthening (p = 0.002) were higher in CMs from TAC-Ucn2 mice, and Tau was reduced (p = 0.001). LV (Ser-16) phosphorylation of phospholamban (PLB) was increased in TAC-Ucn2 mice (p = 0.025), and also was increased in HL-1 cells treated with angiotensin II to induce hypertrophy and incubated with Ucn2 peptide (p = 0.001). Ucn2 gene transfer in TAC-induced heart failure with preserved ejection fraction increased cardiac function in the intact LV and provided corresponding benefits in CMs isolated from study animals, including increased myofilament Ca2+ sensitivity during contraction. The mechanism includes enhanced CM Ca2+ handling associated with increased (Ser-16)-PLB.
Assuntos
Angiotensina II , Urocortinas , Camundongos , Animais , Urocortinas/genética , Urocortinas/metabolismo , Pressão Ventricular , Terapia Genética , Função Ventricular Esquerda/genética , Hipertrofia , Camundongos Endogâmicos C57BLRESUMO
Preclinical models of aortic stenosis can induce left ventricular pressure overload and coarsely control the severity of aortic constriction. However, they do not recapitulate the haemodynamics and flow patterns associated with the disease. Here we report the development of a customizable soft robotic aortic sleeve that can mimic the haemodynamics and biomechanics of aortic stenosis. By allowing for the adjustment of actuation patterns and blood-flow dynamics, the robotic sleeve recapitulates clinically relevant haemodynamics in a porcine model of aortic stenosis, as we show via in vivo echocardiography and catheterization studies, and a combination of in vitro and computational analyses. Using in vivo and in vitro magnetic resonance imaging, we also quantified the four-dimensional blood-flow velocity profiles associated with the disease and with bicommissural and unicommissural defects re-created by the robotic sleeve. The design of the sleeve, which can be adjusted on the basis of computed tomography data, allows for the design of patient-specific devices that may guide clinical decisions and improve the management and treatment of patients with aortic stenosis.
Assuntos
Estenose da Valva Aórtica , Robótica , Suínos , Animais , Fenômenos Biomecânicos , Pressão Ventricular , Estenose da Valva Aórtica/diagnóstico por imagem , HemodinâmicaRESUMO
Left ventricular (LV) catheterization with either a pressure catheter or pressure-volume catheter provides a means to measure cardiac function, an important endpoint in many studies including cardiac gene therapy. While the catheter can be inserted directly into the heart using a surgical approach, utilizing the carotid artery for access has the advantage of being a closed-chest procedure. This negates the need for intubation, prevents myocardial trauma, and preserves normal intrathoracic pressure, providing more accurate assessments of cardiac physiology parameters. We describe a protocol for obtaining carotid artery access and insertion of a pressure-volume catheter into the LV of rodents.
Assuntos
Cateterismo Cardíaco , Função Ventricular Esquerda , Animais , Cateterismo Cardíaco/métodos , Artérias Carótidas , Coração/fisiologia , Ratos , Função Ventricular Esquerda/fisiologia , Pressão VentricularRESUMO
Objective: Left ventricular hypertrophy in aortic stenosis, arterial hypertension or coarctation of the aorta is risk factor for early development of HF. In chronic late compared to early left ventricular afterload increases resulting from descending thoracic оr ascending aorta stenosis, we assess the left ventricular stroke work, pressure-volume area for Ð2 demand and effective work on the 4th and 8th weeks. It is suggested that reduced proximal thoracic aortic compliance presents with myocardial ischemia. However, development of adverse left ventricular hypertrophic remodeling and HF in different peak of LV afterload increase is understood poorly. Methods: Fourteen domestic male pigs (28 ± 3 kg) underwent descending thoracic or ascending aortic stenosis through posterior lateral thoracotomy, with cMRI and an invasive left ventricular pressure-volume loops' аrea assessment (Millar 5Fr pig-tailed conductance catheter) on the 4th and 8th weeks. Left ventricular stroke work and pressure-volume area PVA, parameter for LV O2 demand, were assessed in hypertrophic left ventricular remodeling, resulting from different peaks in LV afterload (late vs. early LV afterload) increase and we thus defined early adverse LV hypertrophic remodeling in linear and nonlinear end-systolic pressure-volume regression analysis. For this we used special software. Data was compared with two-way repeated measures ANOVA. Results presented are means ± (SEM) or medians and significance is set at p < 0.05. Results: The left ventricular nonlinear PVA was not different, in LL compared to EL on the 8th week and when using the linear regression analysis. Stroke work was not different. The linear and nonlinear potential energy were not different between LL vs. the EL group. Nonlinear bLVO2 demand was not different, being higher in LL compared to EL in the 8th week. Indexed PVA parameters were not different or changed between the 4th and 8th weeks, when being normalized for body surface-area (m²) or 100 grams of LV mass. Conclusion: The left ventricular potential energy, PVA with effective work and LVO2 demands are not different in hypertrophic LV remodeling in LL vs. EL group at the 8th week. Difference is not present when end-systolic pressure-volume relation is assessed from indexed LV volumes for m² BSA or 100 grams of LV mass. EL is as important as LL in increased LV afterloads based on LV work and mechanical coupling in this hypertensive heart failure model having preserved EF.
Assuntos
Estenose da Valva Aórtica , Acidente Vascular Cerebral , Aorta Torácica , Pressão Sanguínea , Constrição Patológica , Humanos , Masculino , Suínos , Função Ventricular Esquerda , Pressão VentricularRESUMO
Right ventricular (RV) pressure loading leads to RV and left ventricular (LV) dysfunction through RV hypertrophy, dilatation and fibrosis. Relief of RV pressure load improves RV function. However, the impact and mechanisms on biventricular reverse-remodelling and function are only partially characterized. We evaluated the impact of RV pressure overload relief on biventricular remodelling and function in a rabbit model of reversible pulmonary artery banding (PAB). Rabbits were randomized to three groups: (1) Sham-operated controls (n = 7); (2) PAB (NDef, n = 7); (3) PAB followed by band deflation (Def, n = 5). Sham and NDef animals were sacrificed at 6 weeks after PAB surgery. Def animals underwent PAB deflation at 6 weeks and sacrifice at 9 weeks. Biventricular geometry, function, haemodynamics, hypertrophy and fibrosis were compared between groups using echocardiography, magnetic resonance imaging, high-fidelity pressure-tipped catheters and histology. RV pressure loading caused RV dilatation, systolic dysfunction, myocyte hypertrophy and LV compression which improved after PAB deflation. RV end-diastolic pressure (RVEDP) decreased after PAB deflation, although remaining elevated vs. Sham. LV end-diastolic pressure (LVEDP) was unchanged following PAB deflation. RV and LV collagen volumes in the NDef and Def group were increased vs. Sham, whereas RV and LV collagen volumes were similar between NDef and Def groups. RV myocyte hypertrophy (r = 0.75, P < 0.001) but not collagen volume was related to RVEDP. LV myocyte hypertrophy (r = 0.58, P = 0.016) and collagen volume (r = 0.56, P = 0.031) correlated with LVEDP. In conclusion, relief of RV pressure overload improves RV and LV geometry, hypertrophy and function independent of fibrosis. The long-term implications of persistent fibrosis and increased biventricular filling pressures, even after pressure load relief, need further study. KEY POINTS: Right ventricular (RV) pressure loading in a pulmonary artery banding rabbit model is associated with RV dilatation, left ventricular (LV) compression; biventricular myocyte hypertrophy, fibrosis and dysfunction. The mechanisms and impact of RV pressure load relief on biventricular remodelling and function has not been extensively studied. Relief of RV pressure overload improves biventricular geometry in conjunction with improved RV myocyte hypertrophy and function independent of reduced fibrosis. These findings raise questions as to the importance of fibrosis as a therapeutic target.
Assuntos
Disfunção Ventricular Esquerda , Disfunção Ventricular Direita , Animais , Modelos Animais de Doenças , Fibrose , Ventrículos do Coração , Hipertrofia , Artéria Pulmonar , Coelhos , Disfunção Ventricular Esquerda/complicações , Função Ventricular Direita , Pressão VentricularRESUMO
BACKGROUND: Contemporary data on the independent association of severe tricuspid regurgitation (TR) with excess mortality are needed. The aims of this study were to describe contemporary outcomes of patients with severe TR and to identify outcome modifiers. METHODS: Consecutive echocardiographic reports linked to clinical data from the largest medical center in Israel (2007-2019) were reviewed. The primary outcome was all-cause mortality. Cox regression and propensity score matching models were applied. RESULTS: The final cohort included 97,096 patients. Mild, moderate, and severe TR was documented in 27,147 (28%), 2,844 (3%) and 1,805 (2%) patients, respectively. During a median follow-up period of 5 years (interquartile range, 2-8 years), 22,170 patients (23%) died. Kaplan-Meier survival analysis demonstrated an increased risk for death with an increasing degree of TR (log-rank P < .001). Propensity score matching of 1,265 patients with severe TR and matched control subjects showed that compared with those with nonsevere TR, patients with severe TR were 17% more likely to die (95% CI, 1.05-1.29; P = .003). The association of severe TR with survival was dependent on estimated right ventricular (RV) pressure, with a more pronounced effect among patients with estimated systolic pressure ≤ 40 mm Hg (hazard ratio, 2.12 vs 1.04; P for interaction < .001). A landmark subanalysis of 17,967 patients demonstrated that RV function deterioration on follow-up echocardiography modified the association of severe TR with survival. It was more significant among patients with preserved and stable RV function (P for interaction = .035). CONCLUSIONS: The outcome of severe TR is modified by RV pressure and function. Once RV function deteriorates, differences in the outcomes of patients with and without severe TR are less pronounced.
