Left Ventricular Cardiac Output Research Articles

Efficacy of Beraprost Sodium Combined with Sildenafil and Its Effects on Vascular Endothelial Function and Inflammation in Patients Experiencing Left Heart Failure Complicated with Pulmonary Arterial Hypertension.

BackgroundTo explore the efficacy of beraprost sodium combined with sildenafil and its effects on the vascular endothelial function and inflammation in left heart failure patients complicated with pulmonary arterial hypertension.Material/MethodsA total of 80 patients with left heart failure complicated with pulmonary arterial hypertension was enrolled as the subjects of this study and assigned into an observation group (n=40) and a control group (n=40) using a random number table. The changes in pulmonary arterial hypertension-associated indicators at 3 months after treatment and the alterations in the levels of cardiac function-associated biochemical indicator brain natriuretic peptide (BNP), inflammatory factor tumor necrosis factor alpha (TNF-α), and mean pulmonary arterial pressure during treatment were compared between the 2 groups.ResultsAt 3 months after treatment, the pulmonary arterial hypertension-associated indicators human urotensin II and calcitonin gene-related peptide in the observation group were lower and higher, respectively, than those in control group. Moreover, the observation group had significantly lower BNP and TNF-α levels and mean pulmonary arterial pressure than the control group. After intervention, the echocardiographic parameters left ventricular ejection fraction (LVEF), cardiac output (CO), and stroke volume (SV) in both groups were significantly higher than those before intervention, and the observation group had significantly higher LVEF, SV, and CO than the control group after intervention.ConclusionsBeraprost sodium combined with sildenafil for left heart failure complicated with pulmonary arterial hypertension can effectively improve pulmonary arterial hypertension, alleviate left heart failure, and reduce inflammatory responses, thereby achieving better clinical efficacy in patients.

427 Prenatal prediction of the fetal to neonatal cardiovascular transition

We sought to evaluate changes in the fetal pulmonary artery Doppler following maternal hyperoxygenation during the third trimester of pregnancy and correlate those findings with neonatal echocardiograph indices. Forty-six women with a singleton pregnancy ≥31weeks’ gestational age(GA) were prospectively recruited. Pulsatility index(PI),Resistance index(RI), acceleration time(AT) and ejection time(ET) were measured in the distal fetal pulmonary artery (PA). Doppler measurements were taken at baseline and following maternal hyperoxygenation(MH) for 10minutes.Reactivity to MH was considered where a decrease in PAPI was ≥10% from the baseline. Within 24hours of life a neonatal functional echocardiogram was performed to assess right ventricular systolic pressures,PAAT,ejection fraction(EF) and left ventricular cardiac output(LVCO). The median GA was 35weeks. There was a decrease in fetal PAPI and PARI and an increase in PAAT leading to an increase in AT:ET following MH (Table 1).Fetuses that responded to MH had an increased LVCO and EF. These findings were not dependent on LV size or mitral valve (MV) annular diameter but were related to an increased MV inflow.The PA reactivity was not associated with maternal age, BMI or GA at the time of MH (Table 2).The effect of MH on neonatal LVCO and EF was not dependent on mode of delivery or GA at delivery but on the prenatal response to MH. Maternal hyperoxygenation in the third trimester is associated with significant changes in fetal PA Doppler waveforms.An increased LVCO and EF in the neonates who responded to MH,suggests that MH may prove to be a more reliable predictor of postnatal cardio-pulmonary dysfunction compared to the prenatal evaluation of anatomic structures alone. The response to MH predicted neonatal LVCO suggesting that there is a cohort of infants who may be identified by MH,that may have an increased vulnerability to deal with neonatal illness, due to a limited ability to optimise LV preload. This warrants further exploration to establish the ability of MH to predict the neonatal cardiovascular transition.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Changes in left ventricular size, geometry, pump function and left heart pressures during healthy aging.

There are cross-sectional and longitudinal imaging studies using echocardiography and cardiac magnetic resonance in healthy adult subjects which have demonstrated associations of left ventricular (LV) structure and pump function with age. There are also cross-sectional data regarding the relationships of age with invasively measured left heart chamber pressures. Increasing age is associated with decreases in LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic length (LVEDL), stroke volume (SV) and cardiac output (CO), and increases in relative wall thickness (RWT), LV mass/LVEDV ratio (LVMVR) and ejection fraction (LVEF). Older age is not accompanied by a change in mean left atrial (LA) pressure, but there is both direct and indirect evidence which suggests that LV end-diastolic pressure (LVEDP) increases with age. LVEDV remains lower in older than younger subjects during fluid infusion and the resulting increases in LA pressure. The combination of an increase in LVEF with reductions of both SV and CO demonstrates an age-related increase in divergence between LVEF and LV pump function. A lower LVEDV in older compared to younger subjects can be characterized as an aging-related decrease in LV capacity, with the higher LVEDP in older subjects also indicating a reduction of preload reserve.

Wall shear stress in the thoracic aorta at rest and with dobutamine stress after arterial switch operation.

OBJECTIVESProgressive root dilatation is an important complication in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) that may be caused by altered flow dynamics. Aortic wall shear stress (WSS) distribution at rest and under dobutamine stress (DS) conditions using 4D flow magnetic resonance imaging were investigated in relation to thoracic aorta geometry.METHODS4D flow magnetic resonance imaging was performed in 16 adolescent TGA patients after ASO (rest and DS condition) and in 10 healthy controls (rest). The primary outcome measure was the WSS distribution along the aortic segments and the WSS change with DS in TGA patients. Based on the results, we secondary zoomed in on factors [aortic geometry and left ventricular (LV) function parameters] that might relate to these WSS distribution differences. Aortic diameters, arch angle, LV function parameters (stroke volume, LV ejection fraction, cardiac output) and peak systolic aortic WSS were obtained.RESULTSTGA patients had significantly larger neoaortic root and smaller mid-ascending aorta (AAo) dimensions and aortic arch angle. At rest, patients had significantly higher WSS in the entire thoracic aorta, except for the dilated root. High WSS levels beyond the proximal AAo were associated with the diameter decrease from the root to the mid-AAo (correlation coefficient r = 0.54–0.59, P = 0.022–0.031), not associated with the aortic arch angle. During DS, WSS increased in all aortic segments (P < 0.001), most pronounced in the AAo segments. The increase in LV ejection fraction, stroke volume and cardiac output as a result of DS showed a moderate linear relationship with the WSS increase in the distal AAo (correlation coefficient r = 0.54–0.57, P = 0.002–0.038).CONCLUSIONSIncreased aortic WSS was observed in TGA patients after ASO, related to the ASO-specific geometry, which increased with DS. Stress-enhanced elevated WSS may play a role in neoaortic root dilatation and anterior aortic wall thinning of the distal AAo.

Quantitative assessment of left ventricular volume and function by transthoracic and transesophageal echocardiography, ultrasound velocity dilution, and gated magnetic resonance imaging in healthy foals.

To compare measurements of left ventricular volume and function derived from 2-D transthoracic echocardiography (2DE), transesophageal echocardiography (TEE), and the ultrasound velocity dilution cardiac output method (UDCO) with those derived from cardiac MRI (cMRI) in healthy neonatal foals. 6 healthy 1-week-old Standardbred foals. Foals were anesthetized and underwent 2DE, TEE, and cMRI; UDCO was performed simultaneously with 2DE. Images acquired by 2DE included the right parasternal 4-chamber (R4CH), left apical 4- and 2-chamber (biplane), and right parasternal short-axis M-mode (M-mode) views. The longitudinal 4-chamber view was obtained by TEE. Measurements assessed included left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction, stroke volume (LVSV), cardiac output (CO), and cardiac index (CI). Bland-Altman analyses were used to compare measurements derived from biplane, R4CH, and M-mode images and UDCO with cMRI-derived measurements. Repeatability of measurements calculated by 3 independent reviewers was assessed by the intraclass correlation coefficient. Compared with cMRI, all 2DE and TEE modalities underestimated LVEDV and LVESV and overestimated ejection fraction, CO, and CI. The LVSV was underestimated by the biplane, R4CH, and TEE modalities and overestimated by UDCO and M-mode methods. However, the R4CH-derived LVSV, CO, and CI were clinically comparable to cMRI-derived measures. Repeatability was good to excellent for measures derived from the biplane, R4CH, M-mode, UDCO, and cMRI methods and poor for TEE-derived measures. All assessed modalities yielded clinically acceptable measurements of LVEDV, LVESV, and function, but those measurements should not be used interchangeably when monitoring patient progress.

Echocardiographic assessment of left ventricular size and systolic function in Warmblood horses using linear measurements, area-based indices, and volume estimates: A retrospective database analysis.

BackgroundEchocardiographic assessment of left ventricular (LV) size and function using area‐based indices and volumetric estimates is not well established in horses.ObjectiveTo report reference intervals and measurement variability for uni‐, 2‐, and 3‐dimensional echocardiographic indices of LV size and systolic function in Warmblood horses and to provide proof of concept for allometric scaling of variables to body weight. Unidimensional indices were to be compared to area‐based indices and LV volume estimates to establish their clinical use.AnimalsThirty healthy Warmblood horses and 70 Warmblood horses with a primary diagnosis of mitral regurgitation or aortic regurgitation.MethodsEchocardiographic indices of LV size and systolic function were measured using an existing echocardiography database. Weight‐related variables were scaled to body weight (BWT). Reference intervals and measurement variability were calculated, the influence of valvular regurgitation on LV size and function was investigated and agreement between different variables for detection of reduced, normal, and increased LV size and systolic function was assessed.ResultsReference values for healthy Warmblood horses were reported. Measurement variability was sufficiently low for clinical use of all variables. Allometric scaling was effective to correct diastolic LV dimensions and cardiac output for differences in BWT. Various echocardiographic indices resulted in different conclusions regarding identification of LV enlargement and systolic dysfunction in healthy horses and horses with valvular regurgitation.Conclusions and Clinical ImportanceEchocardiographic assessment of LV size and systolic function should include joint assessment of multiple uni‐ and multidimensional indices. Area‐based or volumetric indices that reflect LV long‐axis motion should be included.

Abstract 15036: Artificial Intelligence for Characterizing Heart Failure in Cardiac Magnetic Resonance Images

Introduction: Congestive heart failure (CHF) increases hospitalization burden and risk of mortality.; However, currently there are no guidelines for preemptive screening for CHF. This study aimed to identify imaging features to classify past CHF in order to predict future CHF in cardiac magnetic resonance images (CMRIs). Hypothesis: Machine learning (ML) may reliably segment the heart chambers from CMRIs and these segmentations yield imaging biomarkers to predict CHF. Methods: This study extracted CMRIs from 350 subjects with and without CHF in the UK Biobank. Participants with no CHF were randomly selected to match those with CHF. Convolutional neural networks (CNNs) segmented the heart in short and long axis CMRIs. Each model was based on VGGNet with added skip connections that perform transposed convolutions. These convolutions upsampled feature maps at each scale and concatenated them at the network’s resolution. The VGGNet learned deep feature representations, while the transposed convolutions compensated for issues underlying network depth. The resulting segmentations and imaging metadata were parsed to extract clinical parameters related to heart measurements and function. Support vector machines (SVM) consistently yielded the highest performance among all ML classifiers. A following step split the data into 80%/20% training/testing and run five-fold cross validation on the training set to select optimal SVM parameters. Linear SVM provided feature weights that corresponded to relative feature importance. Results: The pipeline identified past/current HF with 0.84 accuracy and 0.86 precision. The key features for identifying past/current CHF included left ventricular (LV) end diastolic volume, LV end systolic volume, LV stroke volume, LV ejection fraction (LVEF), LV mass, left atrial volume (LAV) max, and LAV min. Future prediction yielded 0.80 accuracy and 0.80 precision. In comparison, these results resulted in the following key features: LVEF, LV cardiac output, left atrial stroke volume, left atrial ejection fraction. Conclusion: CMRI provides a reliable method of extracting indicators for cardiac measurements and function. These values help capture heart health and predict future heart complications like CHF.

Partial normalisation of cardiac mechanics with active CRT in patients with chronic failure: a novel application of 3.0T CMR

Abstract Introduction Cardiac resynchronisation therapy (CRT) is a routine treatment for chronic heart failure (CHF) with reduced ejection fraction and conduction delay to improve prognosis. Cardiac mechanics in patients with CHF are believed to be altered from controls based on invasive and echocardiographic based data. Technological advancements in cardiac magnetic resonance (CMR) and devices enable investigation of the cardiac response to CRT over a range of heart rates. Methods Patients with a CRT-D device were enrolled from heart failure clinics at Leeds General Infirmary, UK. After a MRI safety assessment, a baseline device check was conducted by a cardiac physiologist. Left ventricular (LV) volumes and systolic BP were measured at baseline and heart rates of 75, 90, 100, 115, 125, and 140 (randomised order) with CRT active and intrinsic conduction. All scans were conducted using a 3.0 T Siemens Prisma MRI scanner. Analysis of the scans used commercially available software. LV contractility was derived as a ratio of the LV end systolic volume and systolic BP. A post scan device interrogation was conducted to assess for scanning safety. Control participants with a 3.0T MR-conditional dual chamber pacemakers completed a similar protocol. Results Scanning was conducted in 17 CRT patients and 13 controls with a pre and post device and lead interrogation. No patient experienced symptoms related to scanning or device failure. The mean LV ejection fraction at baseline in the CRT cohort was 33.7±12.9%. Left ventricular ejection fraction fell across both cohorts as paced heart rate increased with reduced deterioration in control patients and those with CRT active. Peak LV cardiac output was significantly higher during active CRT (p&amp;lt;0.05). LV contractility was relatively static with CRT disabled (r2=0.13, p=0.38) and improved with CRT active (r2=0.91, p=0.01) and in controls (r2=0.74, p=0.01). Peak LV strain occurred at 100bpm during active CRT and in control patients whereas CRT disabled resulted in earlier deterioration. Conclusion We have demonstrated improvements in cardiac output and contractility consequent to active CRT using 3.0T CMR and subsequently validated via strain analysis. CRT appears to partially normalise cardiac mechanics across the range of heart rates studied. Further work is required to explore this phenomenon on a cellular or metabolic level. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AK is supported by an unconditional grant provided by Medtronic

Photoacoustic mapping of tissue hypoxia after myocardial infarction in mice

Introduction Early alterations of microvascular blood flow after myocardial infarction (MI) may participate in the development of multiple organ failure. The aim of this study was to assess the contribution of photoacoustic imaging, a hybrid technology based on laser and ultrasound energy coupling, to detect early oxygen saturation (sO2) impairment in peripheral organs (kidney, liver) after MI in mice. Methods An experimental preclinical study was carried out on two groups of six week BALB/c mice: Sham (n=22) versus MI (n=40). MI was obtained by permanent ligation of the left anterior descending artery within 7 days of follow-up. High resolution ultrasound was used to assess left ventricular (LV) function (ejection fraction (EF), Cardiac Output (CO) and longitudinal strain). Photoacoustic imaging (VevoLAZR, ViualSonics®) was used to measure kinetics of the heart, kidney and liver sO2 after MI. Plasma biomarkers (ASAT, ALAT, creatinine, lactate) were assessed. Results LV function was altered 4h post-MI (LVEF: Sham 61.7% n=16, MI 25.7% n=32, p Discussion Post-MI heart failure generates moderate hypoxia of the peripheral organs in mice. Photoacoustic imaging enables early detection of sO2 multi-organ desaturation. The mapping of sO2 organs in real time seems to be an accurate marker to identify microcirculation alteration. This emerging imaging technology could be used to improve and evaluate early microvascular therapeutics.

The Partial Support of the Left Ventricular Assist Device Shifts the Systemic Cardiac Output Curve Upward in Proportion to the Effective Left Ventricular Ejection Fraction in Pressure-Volume Loop.

Left ventricular assist device (LVAD) has been saving many lives in patients with severe left ventricular (LV) failure. Recently, a minimally invasive transvascular LVAD such as Impella enables us to support unstable hemodynamics in severely ill patients. Although LVAD support increases total LV cardiac output (COTLV) at the expense of decreases in the native LV cardiac output (CONLV), the underlying mechanism determining COTLV remains unestablished. This study aims to clarify the mechanism and develop a framework to predict COTLV under known LVAD flow (COLVAD). We previously developed a generalized framework of circulatory equilibrium that consists of the integrated CO curve and the VR surface as common functions of right atrial pressure (PRA) and left atrial pressure (PLA). The intersection between the integrated CO curve and the VR surface defines circulatory equilibrium. Incorporating LVAD into this framework indicated that LVAD increases afterload, which in turn decreases CONLV. The total LV cardiac output (COTLV) under LVAD support becomes COTLV = CONLV+EFe · COLVAD, where EFe is effective ejection fraction, i.e., Ees/(Ees+Ea). Ees and Ea represent LV end-systolic elastance (Ees) and effective arterial elastance (Ea), respectively. In other words, LVAD shifts the total LV cardiac output curve upward by EFe · COLVAD. In contrast, LVAD does not change the VR surface or the right ventricular CO curve. In six anesthetized dogs, we created LV failure by the coronary ligation of the left anterior descending artery and inserted LVAD by withdrawing blood from LV and pumping out to the femoral artery. We determined the parameters of the CO curve with a volume-change technique. We then changed the COLVAD stepwise from 0 to 70–100 ml/kg/min and predicted hemodynamics by using the proposed circulatory equilibrium. Predicted COTLV, PRA, and PLA for each step correlated well with those measured (SEE; 2.8 ml/kg/min 0.17 mmHg, and 0.65 mmHg, respectively, r2; 0.993, 0.993, and 0.965, respectively). The proposed framework quantitatively predicted the upward-shift of the total CO curve resulting from the synergistic effect of LV systolic function and LVAD support. The proposed framework can contribute to the safe management of patients with LVAD.

Efficacy of methylene blue in a murine model of amlodipine overdose.

Amlodipine overdoses have significant cardiac toxicity and are difficult to treat. Methylene blue has potential as a treatment for overdoses. A randomized controlled study of methylene blue as a treatment for amlodipine toxicity was conducted in C57Bl/6 mice. A baseline echocardiography was followed by gavage administration of amlodipine (90 mg/kg). Five minutes after gavage, animals received either vehicle solution (controls) or methylene blue (20 mg/kg) by intra-peritoneal injection. Animals were continuously monitored, and cardiac parameters were acquired every 15 min up to two hours. Only 50% of control animals survived to the two-hour endpoint compared to 83% that received methylene blue. Amlodipine delivery induced significant reduction in left ventricular ejection fraction (EF), fractional shortening (FS), stroke volume (SV), and cardiac output (CO) in the vehicle treated animals relative to animals in the treatment group (p < 0.05 vehicle versus Methylene blue for EF, FS, SV, CO, and HR). The amlodipine dose induced cardiotoxicity that were effects were more pronounced in the untreated group. 50% vehicle controls quickly progressed into heart failure (within 90 min of exposure) and did not survive the two h observation endpoint. Distinctly, only one animal from the Methylene blue treatment group did not survive (83% survival) the study. Additionally, the surviving animals from the Methylene blue group displayed significantly higher ejection fraction, fractional shortening, stroke volume, and cardiac output compared to vehicle group, indicating that methylene blue preserved cardiac function. In this mouse model of amlodipine overdose, methylene blue decreased cardiac toxicity.

Pharmacodynamic and pharmacokinetic effects of S086, a novel angiotensin receptor neprilysin inhibitor

Background and PurposeAngiotensin receptor-NEP inhibitor (ARNi), which includes an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has been proven safe and effective for treating heart failure with reduced ejection fraction (HF-REF). S086 is a novel single-molecule ARNi that includes the molecular moieties of EXP3174 (the active metabolite of the ARB losartan) and sacubitril (a NEP inhibitor prodrug) in a 1:1 M ratio. We performed preclinical animal model studies to evaluate the efficacy of S086 in treating HF. Experimental ApproachRat and dog models of myocardial ischemia-induced chronic heart failure were used in this research. Principal ResultsThe oral administration of S086 dose-dependently lowered the heart weight index, attenuated cardiac fibrosis, and improved left ventricular ejection fraction, shortening fraction, and cardiac output, without effects on hemodynamics in animal models of myocardial ischemia-induced chronic heart failure. A comparable protective effect to LCZ696 was observed for S086 at an equal molar dose in dog models. In addition, S086 was superior to LCZ696 since it significantly reversed the decrease in left ventricular posterior wall end-systolic thickness. ConclusionThis animal study suggests that S086 is effective in treating myocardial ischemia-induced chronic heart failure.

Right Ventricle Mechanics and Function during Stress in Patients with Asymptomatic Primary Moderate to Severe Mitral Regurgitation and Preserved Left Ventricular Ejection Fraction.

Background and objectives. Mitral regurgitation (MR) is usually dynamic and increasing with exertion. Stress may provoke symptoms, cause the progression of pulmonary hypertension (PH) and unmask subclinical changes of the left and right ventricle function. The aim of this study was to evaluate changes of right ventricle (RV) functional parameters during stress and to find out determinants of RV function in patients with MR. Materials and methods. We performed a prospective study that included patients with asymptomatic primary moderate to severe MR and preserved left ventricular (LV) ejection fraction (EF) at rest (≥60%). Conventional 2D echocardiography at rest and during stress (bicycle ergometry) and offline speckle tracking analysis were performed. Results. 80 patients were included as MR (50) and control (30) groups. Conventional functional and myocardial deformation parameters of RV were similar in both groups at all stages of exercise (p > 0.05). The grade of MR (p = 0.004) and higher LV global longitudinal strain (p = 0.037) contributed significantly to the changes of tricuspid annular plane systolic excursion (TAPSE) from rest to peak stress. Changes of MR ERA from the rest to peak stress were related to RV free wall longitudinal strain (FWLS) and four chambers longitudinal stain (4CLS) at rest (p = 0.011; r = −0.459 and p = 0.001; r = −0.572, respectively). Significant correlations between LV EF, stroke volume, cardiac output and RV fractional area change, S′, TAPSE, FWLS, 4CLS were obtained. However, systolic pulmonary artery pressure and RV functional, deformation parameters were not related (p > 0.05). Conclusions. Functional parameters of LV during exercise and severity of MR were significant determinants of RV function while PH has no correlation with it in patients with primary asymptomatic moderate to severe MR.

Feasibility of ventricular volumetry by cardiovascular MRI to assess cardiac function in the fetal sheep.

The application of fetal cardiovascular magnetic resonance imaging (CMR) to assess fetal cardiovascular physiology and cardiac function through the quantification of ventricular volumes has previously been investigated, but the approach has not yet been fully validated. Ventricular output measurements calculated from heart rate and stroke volumes (SV) of the right and left ventricles measured by ventricular volumetry (VV) exhibited a high level of agreement with phase-contrast (PC) blood flow measurements in the main pulmonary artery and ascending aorta, respectively. Ejection fraction of the right ventricle, which is lower than that of the left ventricle in postnatal subjects, was similar to the left ventricular ejection fraction in the fetus; probably due to the different loading conditions present in the fetal circulation. This study provides evidence to support the reliability of VV in the sheep fetus, providing evidence for its use in animal models of human diseases affecting the fetal circulation. The application of ventricular volumetry (VV) by cardiovascular magnetic resonance imaging (CMR) in the fetus remains challenging due to the small size of the fetal heart and high heart rate. The reliability of this technique in utero has not yet been established. The aim of this study was to assess the feasibility and reliability of VV in a fetal sheep model of human pregnancy. Right and left ventricular outputs by stroke volume (SV) measured using VV were compared with 2D phase-contrast (PC) CMR measurements of blood flow in the main pulmonary artery (MPA) and ascending aorta (AAo). At 124-140days (d) gestation, singleton bearing Merino ewes underwent CMR under general anaesthesia using fetal femoral artery catheters, implanted at 109-117d, to trigger cine steady state free precession acquisitions of ventricular short-axis stacks. The short-axis cine stacks were segmented at end-systole and end-diastole, yielding right and left ventricular SV, ejection fraction, and cardiac outputs (SV×heart rate). PC cine acquisitions of MPA and AAo were analysed to measure blood flow, which served as comparators for the right and left cardiac outputs by VV. There was good correlation and agreement between VV and PC measures of ventricular outputs with no significant bias (r2 =0.926; P<0.0001; Bias=-4.7±10.5mlmin-1 kg-1 ; 95% limits of agreement: -15.9 to 25.2mlmin-1 kg-1 ). This study validates fetal VV by CMR in a large animal model of human pregnancy and provides preliminary reference values of fetal sheep right and left ventricles in late gestation.

P1322EFFECTS OF HAEMODIALYSIS ARTERIOVENOUS FISTULA CREATION ON CARDIAC STRUCTURE AND FUNCTION

Abstract Background and Aims Arteriovenous fistula (AVF) is considered the preferred type of access for maintenance haemodialysis. The creation of an AVF may contribute to maladaptive cardiovascular remodelling. We conducted a study to evaluate the effect of AVF creation on cardiac structure and function in patients with end-stage renal disease (ESRD). Method In this prospective cohort study, patients with ESRD listed for AVF creation underwent cardiac magnetic resonance imaging at baseline and at 6 weeks. All participants had ultrasound measurements of AVF blood flow at 6 weeks. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, left atrial volume, LV ejection fraction, LV global longitudinal strain, cardiac output/index, and septal thickness. Results A total of 65 patients were enrolled, of whom 40 had an AVF creation and completed both scans. Patients were divided into 2 groups based on AVF blood flows: 22 in the high flow group (≥ 600mL/min) and 18 in the low flow group (&amp;lt; 600mL/min). On the second cardiac magnetic resonance scan, a mean increase of 7.4 g (95% CI, 1.1–13.7, P=0.02) was observed in LV mass; in the high flow group the mean increase was 15.5 g (95% CI, 7.3–23.8) compared with a small decrease of 2.5 g (95% CI, −10.6 to 5.6) in the low flow group (P=0.003). Significant increases in LV end-diastolic volumes, cardiac output, and cardiac index were also seen after AVF creation (P&amp;lt;0.04). No significant changes were observed in LV ejection fraction (P=0.52), LV end-systolic volumes (P=0.12), and LV global longitudinal strain (P=0.21). Conclusion Creation of AVF in adults with ESRD resulted in significant increase of LV myocardial mass early after surgery.

SAT-550 Changes in Albuminuria Precede Dietary Sodium-Dependent Changes in BP During Aging - a Longitudinal Study

Background: Hypertension (HT) is a well-established independent risk factor for adverse cardiovascular and renal (CVR) outcomes and a high salt (HS) diet is the main cause for high blood pressure (BP). Despite extensive research focusing on HT, surprisingly there are no longitudinal studies assessing the long-term effects of HS. Aims: This study aimed (1) to evaluate the timing of onset for changes in CVR health during long-term sodium loading and (2) to assess whether salt restriction can prevent these effects. Methods: C57BL/6 mice were randomized to HS, moderate (NS) or low (LS) salt diet and followed longitudinally for 50 weeks (wks). BP, urinary albumin/creatinine ratio (AC), plasma aldosterone (PA) and renin activity (PRA) were assessed monthly. At the end of the study, renal artery resistance and left ventricular (LV) parameters were measured by ultrasound and echocardiogram. Renal AT1 expression (Western Blot) and activity (IHQ) were quantified. Results: At the beginning of the study, there were no differences in BP and AC between the three dietary groups. Relative to wk 1, BP (mmHg) in the HS group was higher in wk 21 (131±1.7 vs. 115±3.0, p= 0.05). Sodium restriction delayed this increase: SBP was higher in wk 41 in the NS group compared to the wk 1 (128±3.4 vs. 115±6.4, p= 0.05) but did not reach significance in the LS group until the end of the study. Similarly, relative to wk 1, AC (µg/mg) only in the HS group reached significantly higher levels in wk 17 (44±4.2, p<0.05). Again, sodium restriction delayed the occurrence of renal damage. AC reached significance in wks 25 and 41 for NS and LS (35±1.1 and 42±2.6 respectively, p<0.05 vs. baseline). Interestingly, the changes in AC always preceded the changes in BP, irrespective of diet. PA and PRA were appropriately activated by dietary salt restriction and suppressed by aging. The aging-induced suppression appeared stronger for PA than for PRA in the HS group only. Long-term sodium loading (HS) induced increased renal resistance, which was prevented in the LS but not in the NS group. Relative to HS, the LV mass index and cardiac output were lower in the NS and LS groups (p<0.05). LV volume indices and ejection fraction did not differ between groups. Renal AT1 protein expression and activation status (IHQ) were decreased in the sodium restricted group. Conclusions: Our study showed that long-term exposure to HS induced a progressive increase in BP and AC in mice. Importantly, these changes were delayed by long-term reduction in sodium intake. Interestingly, changes in AC preceded those in BP, irrespective of diet. Cardiac parameters suggest a sodium-induced eccentric cardiac hypertrophy in the older age, which was prevented by sodium restriction. One possible mechanism behind these effects is the overactivation of the AT1 receptor pathway.

Maternal azithromycin therapy for Ureaplasma parvum intraamniotic infection improves fetal hemodynamics in a nonhuman primate model

Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases. This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes. Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (107 colony-forming units/mL, n=15), and intraamniotic infection plus azithromycin treatment (12.5 mg/kg twice a day intravenously, n=8) groups. At approximately 135 days' gestation (term=165 days), pulsed and color Doppler ultrasonography was used to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebroplacental ratio, and left and right ventricular cardiac outputs) and cardiac function (ratio of peak early vs late transmitral flow velocity [marker of ventricular function], Tei index [myocardial performance index]). These indices were stratified by amniotic fluid proinflammatory mediator levels and cardiac histology. Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P<.05). Azithromycin treatment restored values to control levels. Amniotic fluid prostaglandin F2 alpha levels were significantly higher in animals with abnormal umbilical artery pulsatility index (>1.1) than in those with normal blood flow (P<.05; Spearman ρ=0.6, P<.05). In the intraamniotic inoculation with Ureaplasma parvum group, left ventricular cardiac output was significantly decreased (P<.001), and more animals had abnormal right-to-left ventricular cardiac output ratios (defined as >1.6, P<.05). Amniotic fluid interleukin-6 concentrations were elevated in cases of abnormal right-to-left ventricular cardiac output ratios compared with those in normal cases (P<.05). Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.

The Regulation of Heme Metabolism in Myocytes by Hypoxia and Ischemia: Substrate‐Enzyme Dyssynchrony

Current strategies for the treatment of acute myocardial infarction (AMI) are limited therefore better pharmacological interventions are needed to improve cardiac function post‐injury. Overexpression of the enzyme heme oxygenase‐1 (HMOX1) has been shown to exert cytoprotective effects in models of acute myocardial infarction and represents a highly attractive therapeutic target. HMOX1 is the stress‐inducible enzyme responsible for the catabolism of heme, the functional backbone by which oxygen is carried in proteins like hemoglobin and cytochromes in the electron transport chain. As a potent inducer of HMOX1 and an FDA‐approved heme‐surrogate for the treatment of porphyria, hemin represents a novel treatment strategy for AMI.Translation of HMOX1‐targeted therapeutics to the clinic has been stymied by a singular focus on HMOX1 and an incomplete understanding of fundamental heme metabolism regulation in response to hypoxia, ischemia or pharmacological stimulation with hemin. To date, studies investigating hemin pharmacology and its use in models of ischemic injury are limited. The objective of the present study was to provide a temporal and pharmacokinetic characterization of the changes in heme regulatory enzyme expression in response to hemin and ischemic cardiac injury (i.e. AMI).Echocardiographic, hemodynamic and protein quantification analyses were performed in male CD‐1 mice following a single intraperitoneal hemin injection, permanent ligation AMI, or daily hemin treatment pre‐ or post‐AMI with corresponding sham and vehicle controls. Temporal changes in left ventricular heme regulatory enzyme expression were measured in response to hemin and AMI. This is the first study to holistically characterize the effects of either AMI and/or hemin on endogenous heme regulation in the myocardium.Hemin markedly increased HMOX1 levels and instigated isoform switching between heme‐synthesizing enzymes in the left ventricle of healthy mice. This isoform switching was further observed with AMI and suggests a progressive increase in heme bioavailability with ischemic injury. Interestingly, HMOX1 — a heme and stress‐inducible enzyme — was induced at only 3 days post‐AMI and did not increase concomitantly with heme‐synthesizing enzymes.Echocardiographic analyses showed preserved left ventricular morphology and cardiac output with hemin administration both pre‐ and post‐AMI. Invasive hemodynamics revealed preserved left ventricular function in mice administered daily hemin when initiated 3h pre‐AMI but not when initiated 2h post‐AMI. Similarly, hemin administration significantly increased H9C2 cardiomyotubule viability when administered prior to H2O2‐mediated injury but not with simultaneous or 2h post‐injury hemin administration. This suggests that time‐dependent mechanisms are involved in conferring hemin‐mediated cardioprotection and could suggest differential mechanisms related to myocyte survival and cardiac remodelling.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Nova Scotia Health Research Foundation

Nutraceutical support in heart failure: a position paper of the International Lipid Expert Panel (ILEP).

Heart failure (HF) is a complex clinical syndrome that represents a major cause of morbidity and mortality in Western countries. Several nutraceuticals have shown interesting clinical results in HF prevention as well as in the treatment of the early stages of the disease, alone or in combination with pharmacological therapy. The aim of the present expert opinion position paper is to summarise the available clinical evidence on the role of phytochemicals in HF prevention and/or treatment that might be considered in those patients not treated optimally as well as in those with low therapy adherence. The level of evidence and the strength of recommendation of particular HF treatment options were weighed up and graded according to predefined scales. A systematic search strategy was developed to identify trials in PubMed (January 1970 to June 2019). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' or 'left verntricular dysfunction' were used in the literature search. The experts discussed and agreed on the recommendation levels. Available clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, l-carnitine, d-ribose, carnosine, vitamin D, probiotics, n-3 PUFA and beet nitrates) might be associated with improvements in self-perceived quality of life and/or functional parameters such as left ventricular ejection fraction, stroke volume and cardiac output in HF patients, with minimal or no side effects. Those benefits tended to be greater in earlier HF stages. Available clinical evidence supports the usefulness of supplementation with some nutraceuticals to improve HF management in addition to evidence-based pharmacological therapy.

Left ventricular unloading during extracorporeal membrane oxygenation - Impella versus atrial septal defect: A simulation study.

Atrial septal defect and Impella have been proposed for left ventricular unloading in venoarterial extracorporeal membrane oxygenation patients. This work aims at evaluating the haemodynamic changes in venoarterial extracorporeal membrane oxygenation patients after Impella implantation or atrial septal defect realization by a simulation study. A lumped parameter model of the cardiovascular system was adapted to this study. Atrial septal defect was modelled as a resistance between the two atria. Venoarterial extracorporeal membrane oxygenation and Impella were modelled starting from their pressure-flow characteristics. The baseline condition of a patient undergoing venoarterial extracorporeal membrane oxygenation was reproduced starting from haemodynamic and echocardiographic data. The effects of different atrial septal defect size, Impella and venoarterial extracorporeal membrane oxygenation support were simulated. Impella caused an increment of mean arterial pressure up to 67%, a decrement in mean pulmonary arterial pressure up to 8%, a decrement in left ventricular end systolic volume up to 11% with a reduction up to 97% of left ventricular cardiac output. Atrial septal defect reduces left atrial pressure (19%), increases right atrial pressure (22%), increases mean arterial pressure (18%), decreases left ventricular end systolic volume (11%), increases right ventricular volume (33%) and decreases left ventricular cardiac output (55%). Impella has a higher capability in left ventricular unloading during venoarterial extracorporeal membrane oxygenation in comparison to atrial septal defect with a lower right ventricular overload.