Conduit Arteries Research Articles

BiGRU-attention for Continuous blood pressure trends estimation through single channel PPG

BackgroundPhysiological parameter monitoring based on photoplethysmography (PPG) detection has the advantage of fast, portable, and non-invasive. Changes in the morphology of the PPG waveform can reflect the effect of arterial elasticity changes on blood pressure (BP). However, machine learning models and non-recurrent neural network models typically ignore the time-dependency of continuous PPG data, leading to the decrease of accuracy or the increased calibration frequency. ObjectiveThis paper proposes a BiGRU model with attention to estimate BP trends, which uses a single-channel PPG signal combined with demographic information to estimate continuous BP trends point-by-point and to discuss the impact of calibration cycle. MethodsThis paper selects 15 typical subjects from two groups with/without cardiovascular disease (CVD) and evaluates the model performance. Regarding the calibration frequency problem, we set two modes of non-calibration and calibration to validate the results of blood pressure trends estimation. ResultsIn the calibration mode, the estimation errors (ME ± STD) of SBP for CVD/non-CVD groups are 0.91 ± 10.58 mmHg/0.17 ± 10.06 mmHg respectively, and DBP are 0.34 ± 5.28 mmHg/-0.19 ± 5.36 mmHg; in the non-calibration mode, the estimation errors of SBP for CVD/non-CVD groups are 0.27 ± 9.87 mmHg/-0.82 ± 9.92 mmHg respectively, and DBP are −0.63 ± 3.28 mmHg/0.80 ± 4.93 mmHg. ConclusionsThe results show that the proposed model has high accuracy in estimating BP levels, which is expected to achieve real-time, long-term continuous BP trends monitoring in wearable devices.

Effect of using hypotension prediction index versus conventional goal-directed haemodynamic management to reduce intraoperative hypotension in non-cardiac surgery: A randomised controlled trial

Study objectiveIt remains unclear whether it is the hypotension prediction index itself or goal-directed haemodynamic therapy that mitigates intraoperative hypotension. DesignA single centre randomised controlled trial. SettingSapporo Medical University Hospital. PatientsA total of 64 adults patients undergoing major non-cardiac surgery under general anaesthesia. InterventionsPatients were randomly assigned to either group receiving conventional goal-directed therapy (FloTrac group) or combination of the hypotension prediction index and conventional goal-directed therapy (HPI group). To investigate the independent utility of the index, the peak rates of arterial pressure and dynamic arterial elastance were not included in the treatment algorithm for the HPI group. MeasurementsThe primary outcome was the time-weighted average of the areas under the threshold. Secondary outcomes were area under the threshold, the number of hypotension events, total duration of hypotension events, mean mean arterial pressure during the hypotension period, number of hypotension events with mean arterial pressure < 50 mmHg, amounts of fluids, blood products, blood loss, and urine output, frequency and amount of vasoactive agents, concentration of haemoglobin during the monitoring period, and 30-day mortality. Main resultsThe time-weighted average of the area below the threshold was lower in the HPI group than in the control group; 0.19 mmHg (interquartile range, 0.06–0.80 mmHg) vs. 0.66 mmHg (0.28–1.67 mmHg), with a median difference of −0.41 mmHg (95% confidence interval, −0.69 to −0.10 mmHg), p = 0.005. Norepinephrine was administered to 12 (40%) and 5 (17%) patients in the HPI and FloTrac groups, respectively (p = 0.045). No significant differences were observed in the volumes of fluid and blood products between the study groups. ConclusionsThe current randomised controlled trial results suggest that using the hypotension prediction index independently lowered the cumulative amount of intraoperative hypotension during major non-cardiac surgery.

Effect of the Duration of Restrictive Fluid Therapy on Acute Kidney Injury in Robot-Assisted Laparoscopic Prostatectomy.

In robot-assisted laparoscopic prostatectomy (RALP), restrictive fluid therapy (RFT) is often utilized until the vesicourethral anastomosis (console period) is completed. RFT can cause acute kidney injury (AKI). Thus, RFT prolongation in surgeries that utilize the Trendelenburg position and pneumoperitoneum may increase the risk of postoperative AKI. We aimed to evaluate the effect of RFT duration on postoperative AKI. Forty-four patients who underwent RALP were included in this prospective observational study. Patients were divided into two groups according to the RFT duration (Group I, RFT duration ≤ 3 h, and Group II, RFT duration >3 h). AKI was diagnosed and staged according to the Kidney Disease Improving Global Outcomes criteria (KDIGO) using patients' serum creatinine levels after the first 24 h postoperatively. Hemodynamic parameters were monitored using the pressure recording analytical method. The AKI incidence was significantly higher in Group II than in Group I (45.5% vs. 9.1%; p = 0.016). In both groups, all patients who developed AKI were KDIGO stage 1 and all recovered on the second postoperative day. At the end of the console period, the heart rate and arterial elastance were significantly higher, whereas the stroke volume index was significantly lower in Group II than in Group I (p = 0.041, p = 0.016, and p < 0.001, respectively). Although the amounts of fluid administered before and after the anastomosis were similar between the groups, the total amount of fluid administered was significantly different (p < 0.001). There was a significant negative correlation between RFT duration and the total amount of fluid administered (r2 = 0.43, p < 0.001). RFT duration of >3 h, total fluid administration of ≤3.3 mL/kg/h, and stroke volume index (SVI) at the end of the console period of ≤32 mL/m2 increased the risk of AKI by 12.0 times (1.7-85.2) (p = 0.013). RFT prolongation in RALP may increase the risk of developing AKI.

Occult right ventricular dysfunction and right ventricular-vascular uncoupling in left ventricular assist device recipients

BackgroundCurrent assessments remain insensitive for detecting right heart failure post left ventricular assist device (LVAD). Sensitive pressure-volume loop assessments of right ventricle (RV) contractility may improve our appreciation of post-LVAD RV dysfunction. MethodsThirteen LVAD patients and 20 reference (non-LVAD) subjects underwent comparison of echocardiographic, right heart cath hemodynamic, and pressure-volume loop-derived assessments of RV contractility using end-systolic elastance (Ees), RV afterload by effective arterial elastance (Ea), and RV-pulmonary arterial (RV-PA) coupling (ratio of Ees/Ea). ResultsLVAD patients had lower RV Ees (0.20±0.08 vs. 0.30±0.15 mmHg/ml, p=0.01) and lower RV Ees/Ea (0.37±0.14 vs 1.20±0.54, p<0.001) versus reference subjects. Low RV Ees correlated with reduced RV septal strain, an indicator of septal contractility, in both the entire cohort (r=0.68, p=0.004) as well as the LVAD cohort itself (r=0.78, p=0.02). LVAD recipients with low RV Ees/Ea (below the median value) demonstrated more clinical heart failure (71% vs 17%, p=0.048), driven by an inability to augment RV Ees (0.22±0.11 vs 0.19±0.02 mmHg/ml, p=0.95) to accommodate higher RV Ea (0.82±0.38 vs 0.39±0.08 mmHg/ml, p=0.002). Pulmonary artery pulsatility index (PAPi) best identified low baseline RV Ees/Ea (≤0.35) in LVAD patients (AUC=0.80); during ramp study, change in PAPi also correlated with change in RV Ees/Ea (r=0.58, p=0.04). ConclusionsLVAD patients demonstrate occult intrinsic RV dysfunction. In the setting of excess RV afterload, LVAD patients lack the RV contractile reserve to maintain ventriculo-vascular coupling. Depression in RV contractility may be related to LVAD LV unloading which reduces septal contractility.

Noninvasive Evaluation of Central Haemodynamic Parameters

Ageing is one of the relevant cardiovascular risk factors. Non-invasive assessment of cardiac function is an important approach in preventive medicine. The aim of our study was to evaluate the effect of age and gender on central haemodynamics. Seventy-six clinically healthy individuals were divided into four groups according to their age and gender. Applanation tonometry was applied using Sphygmocor device (AtCor, Australia). Pulse wave analysis was utilized for non-invasive assessment of central pressures (systolic, diastolic, mean, pulse, augmentation and end-systolic). Several important derivative indices such as augmentation index AIx75 $$(\frac{\rm Augmentation\ pressure}{\rm Pulse\ pressure}\times 100$$, corrected for heart rate 75 beats/minute), arterial elastance (Ea,$$\frac{\rm End - systolic\ pressure}{\rm Stroke\ volume})$$ and wasted effort (Ew) were computed. Ew is the ventricular force that is generated to overcome the late systolic peak and does not contribute to an increased stroke volume. Arterial stiffening was confirmed by the significantly higher central systolic and pulse pressures, AIx75 and arterial elastance in the middle-aged groups ($$P&lt;0.01$$). Those alterations were most pronounced in middle-aged females in support to the concept for a postmenopausal effect of female gender beyond ageing. We have shown a positive correlation between Ew and Ea valid only for the middle-aged individuals ($$R=0.70$$, $$P&lt;0.001$$) that coincided with similar correlation between Ea and AIx75 for the same age groups ($$R=0.53$$, $$P&lt;0.001$$). Our supposition is that arterial stiffening contributes to the elevation of the `pulsatile' afterload thus impairing vascular/ventricular coupling and increasing myocardial load and oxygen demands. In conclusion, applanation tonometry and PWA provide reliable measures of central haemodynamics and myocardial afterload.

High Cardio-Ankle Vascular Index Values in Idiopathic Sudden Sensorineural Hearing Loss Patients Indicate Better Prognosis.

Vascular disorders and viral infections are the presumed etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) and acute sensorineural hearing loss, with no identifiable cause. However, no clinical test for estimating the extent of vascular involvement in ISSNHL has been reported despite its potential impact on prognosis and treatment. We investigated the correlation between the cardio-ankle vascular index (CAVI), which reflects arterial stiffness and elasticity, and hearing improvement to ascertain its usefulness as an additional indicator of ISSNHL prognosis and etiology. We enrolled 182 patients diagnosed with definite ISSNHL. The percentage of mild ISSNHL patients and that of patients experiencing no change were compared between the high-CAVI and low-CAVI groups. Age, initial and final pure-tone average (PTA) values, CAVI, presence or absence of vertigo, and medical histories were retrospectively reviewed and included in univariate and multivariate analyses. The percentage of mild ISSNHL patients was smaller in the high-CAVI group than in the low-CAVI group, whereas the percentage of patients experiencing no change was smaller in the high-CAVI group than in the low-CAVI group, although patients in the high-CAVI group were significantly older than those in the low-CAVI group. The Cox proportional hazard model revealed that high CAVI, hypertension, younger age, and initial PTA <90 dB were associated with hearing improvement. ISSNHL in patients with high CAVI was more severe but had a better prognosis than that in those with low CAVI. CAVI may help evaluate diseases of vascular and other etiologies, as well as ISSNHL.

Beyond the Cardiovascular Effects of Glucagon-like Peptide-1 Receptor Agonists: Body Slimming and Plaque Stabilization. Are New Statins Born?

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.

Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease. We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries. In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures. The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies.

Higher Cardio-Ankle Vascular Index Values in Patients With Vestibular Neuritis May Indicate a Better Prognosis.

The presumed etiology of vestibular neuritis (VN), a sudden onset of spontaneous vertigo without auditory or cranial nerve symptoms, includes viral infections and vascular disorders. However, no clinical test for estimating vascular disorders in VN has been reported. Moreover, estimating the etiology of VN is important to predict the prognosis and select appropriate treatment. This study aimed to evaluate the cardio-ankle vascular index (CAVI), which reflects arterial stiffness and elasticity, as an additional indicator for estimating the prognosis and etiology of VN. Among 207 consecutive patients with suspected VN, 88 patients diagnosed with definite VN were enrolled. Age, initial and final percent canal paresis (CP) in the caloric test, CAVI, presence or absence of vestibular-evoked myogenic potential asymmetry, and medical history were evaluated using univariate and multivariate analyses. Patients with VN with high CAVI had a better prognosis than those with low CAVI. High CAVI was a factor for improvement in percent CP, in addition to younger age and less severe initial percent CP in the Cox proportional hazard model. CAVI can be an additional indicator for estimating the prognosis and etiology of VN. This indicator can potentially be applied to other diseases, including vascular disorders with other etiologies.

Changes in common carotid artery elasticity in solid organ recipients

Background. Cardiovascular diseases are very common among solid organ recipients. They are associated with worsening transplant outcomes. Arterial vascular wall elasticity is an important prognostic indicator and a risk marker for cardiovascular events. Noninvasive measurement of common carotid artery (CCA) elasticity may be useful in assessing cardiovascular risk in solid organ recipients.Objective: To conduct a comparative analysis of indicators of CCA elasticity in solid organ recipients and to study their relationship with factors that potentially have a negative impact on the risk of adverse events.Materials and methods. The study included 154 patients aged 10 to 75 years, including heart (n = 77), liver (n = 9), and kidney (n = 35) recipients, as well as 33 patients with end-stage heart failure waitlisted for heart transplantation (HT). In all participants, carotid artery ultrasound was performed, pulse wave velocity was measured, and CCA elasticity was calculated.Results. CCA elasticity was found to be strongly inversely correlated with age, body mass index, systolic blood pressure, renal tubular filtration rate, CCA intima media thickness, and aortic pulse wave velocity. In heart recipients, CCA elasticity was significantly lower than in liver and kidney recipients (p = 0,002) and it inversely correlated with the length of time elapsed after transplantation, which is probably associated with cardiac denervation.Conclusion. CCA elasticity calculated via noninvasive ultrasound reflects the degree of adverse effects of pathological factors on the main arteries in solid organ recipients.

Association between speckle tracking echocardiography and pressure-volume loop derived parameters at increasing levels of myocardial damage in a porcine model of acute cardiogenic shock

Abstract Background Echocardiography is a diagnostic cornerstone in acute cardiovascular care. However, the relationship between speckle tracking assessed global longitudinal strain (LS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops remains poorly elucidated, especially with increasing levels of myocardial damage. Objectives We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central hemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction. Methods Twelve Danish landrace pigs weighing 75-80 kg were used. All instrumentations were performed percutaneously, including placement of a conductance catheter in the LV. Progressive LV dysfunction was induced by stepwise embolization trough the left main coronary artery every three minutes until a 50% reduction in cardiac output or mixed venous saturation, compared to baseline, or a mixed venous saturation &amp;lt;30%. Echocardiography was performed through a subxiphoid midline incision, and was done at baseline and 90 seconds after each injection. Results With progressive LV dysfunction, mean cardiac output decreased from 5.6 l/min (SD: 0.9) to 2.1 l/min (SD: 0.9) and mean mixed venous saturation deteriorated from 61.1%(SD: 7.9) to 35.3% (SD: 6.1). Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8% (SD 3.0) to -6.1% (SD: 2.0) and 16.9 cm (SD: 2.6) to 7.8 cm (SD: 1.8), respectively (Figure 1). LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted univariate regression (r2=0.53 and r2=0.49, respectively. p&amp;lt;0.01 for both). LS correlated significantly, but modest, with stroke volume (r2=0.46, p&amp;lt;0.01), end-systolic elastance (r2=0.32, p&amp;lt;0.01), systolic blood pressure (r2=0.37, p&amp;lt;0.01), ventriculo-arterial coupling(r2=0.34, p&amp;lt;0.01), and arterial elastance (r2=0.23, p&amp;lt;0.01) (Figure 2). In a multivariate regression analysis, LS showed significant correlation with stroke work, systolic blood pressure, and end-diastolic wall stress (r2=0.60, p&amp;lt;0.01). Conclusion In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and LS showed moderate correlations with contractility, arterial elastance and ventriculo-arterial coupling. This indicates that LS is a marker of overall ventricular performance.Echocardiographic changes from baselineScatter plot of LS and hemodynamics

Transcatheter-edge-to-edge-repair of functional mitral regurgitation in advanced HFrEF: the impact of intrinsic left ventricular performance on the degree of MR reduction and clinical outcome

Abstract Background Transcatheter-edge-to-edge-repair (TEER) of functional mitral regurgitation (FMR) reduces rehospitalisation and all-cause mortality in patients with HFrEF/HFmrEF. Not conclusively clarified is the interaction of pre-interventional intrinsic left ventricular (LV) function with TEER success and clinical outcome. By using the gold standard of LV contractility analysis, the invasive pressure-volume loop technique, we examined the interaction of pre-and post-interventional intrinsic LV performance with the degree of MR reduction and all-cause mortality after TEER in patients with advanced HFrEF. Methods In a prospective study of 71 patients with advanced HFrEF (median EF 26%, 22-31%) and severe FMR, we quantified different intrinsic parameters of LV performance by PV-loop analysis (single beat analysis) pre-and post-interventionally. Results In 83% of the patients a MR reduction to grad &amp;lt; 2 could be achieved (hospital discharge). In the ROC analysis, the best cut-off to separate medium-term survival from all-cause mortality (median FU 2.9 years) was a post-interventional regurgitation fraction (RF) &amp;lt; 20% (AUC 0.72, p&amp;lt;0.001, sensitivity 83%, specificity 60%) and a R-volume (RV) &amp;lt; 18ml (AUC 0,7, p=0.002, sensitivity 67%, specificity 72%). The PV-loop-derived intrinsic LV contractility (LV-endsystolic elastance, Ees), LV afterload (arterial elastance, Ea), LV-Ao-coupling (Ees/Ea), LV-mechanical efficacy (ME), PV-loop area (PVA), stroke work, Tau; end-diastolic elastance (Eed), LVEF, LVEDV, and LVESV, pre- and post-TEER, were not predictive for the extent of MR reduction acutely, after 6 months FU, and for all-cause mortality. In multivariate cox-regression analysis, only a post-interventional RF&amp;lt;20% (HR 0.36, p=0.017) or RV&amp;lt;18ml (HR 0.32, p=0.005) and the pre-interventional LV-contractile reserve (LV-CR: post-extra-systolic augmentation of LV-Ees) remained independent predictors of all-cause mortality. In a second model, we included the degree of LV-remodeling (LV-R: LVESV reduction from hospital discharge to 6 months) in the model. In addition to pre-interventional LV-CR, and RF&amp;lt;20%, the LV-R remains independent predictive for all-cause mortality. Conclusion In our peri-mitral-TEER LV-PV-loop study, only the extent of MR reduction and the pre-interventional LV-CR, but not the intrinsic LV performance at rest, determine the medium-term survival of patients with advanced HFrEF and FMR. TEER-mediated MR reduction itself seems not be determined by the LV performance.

Impact of collateral vessels on Fontan circulation by using 0-1 dimensional Fontan circulation model considering concepts of oxygen supply and consumption

Abstract Background/Purpose In patients with univentricular heart disease, the Fontan operation has played a significant role in improving cyanosis and reducing the volume load on the systemic ventricle. However, Fontan patients may develop various complications, and their hemodynamics may deteriorate gradually, resulting in a poor long-term survival rate. Development of collateral vessels before and/or after the Fontan operation is one of the significant problems, and the patients may suffer from advanced cyanosis and heart failure. Although recent studies about the collateral vessels by MRI showed that a significant amount of blood is flown through the collateral vessels, little is known about its effect on the Fontan circulation. Therefore, understanding the mechanism and impact of collateral vessels on the Fontan circulation is important. Methods A 0-1-dimensional Fontan circulation hemodynamic model was developed to reproduce the hemodynamic changes of the blood flow in the entire body by introducing two types of collateral vessels (VVC: veno-venous collateral, APC: aorto-pulmonary collateral) into the model considering clinical status. Also, giving various conditions by ranging catecholamine dose and introducing the concept of oxygen delivery and consumption by changing workloads, arterial and central venous oxygen saturations (SaO2 and SvO2) are predicted in the Fontan circulation models. To evaluate the cardiac function, considering the impact of collateral vessels, four representative values were examined: (1) cardiac output (CO) per minute; (2) Ees relative to arterial elastance (Ees/Ea); (3) ejection fraction; and (4) the stroke work (SW) to pressure-volume area (PVA) ratio (SW/PVA). Results SaO2 and SvO2 were less in Fontan circulations with both VVC and APC present (92% and 54%) than those without collateral vessels (96% and 62%). Also, with collateral vessels, Ees/Ea was decreased while SW/PVA was increased, leading to poor perfusion to the tissue. Regardless of the presence or absence of collateral circulation, SaO2 and SvO2, and systemic blood flow rate decreased when pulmonary vascular resistance was high. By administering catecholamine at 10 microgram/kg/min, in the presence of both VVC and APC, SvO2 was increased from 53% to 58%, while SaO2 was decreased from 92% to 88%. Conclusions The simulated results of arterial and venous blood oxygen saturations and systemic blood flow rate were well-reproduced, matching the previously reported clinical results. It is suggested that pulmonary vasodilators may be beneficial in increasing blood oxygen saturation and improving tissue perfusion, even in Fontan patients with collateral vessels. However, the catecholamine's positive effect is limited. For reproducing various conditions of Fontan circulations, it is necessary to collect actual measurement data from a variety of patients and validate the predicted value to increase the credibility of the model.Arterial and venous oxygen saturationsPressure and volume curves

The acute hemodynamic effects of sodium lactate infusion: increased cardiac output and decreased afterload in a randomized trial in pigs

Abstract Background Lactate is traditionally acknowledged as a by-product of anaerobic glucose metabolism. Recently, however, lactate has been proven to be a preferred oxidative substrate for stressed myocardium. Studies have shown that exogenous lactate infusion provides beneficial hemodynamic effects including increased cardiac output (CO). Nevertheless, the exact mechanism of action underlying the hemodynamic effects of lactate infusion has not been fully elucidated. Aim To identify the cardiovascular mechanisms behind the acute hemodynamic effects of exogenous sodium lactate infusion in an experimental model of healthy human-sized pigs. Methods We performed a randomized, assessor-blinded crossover study in eight female 60 kg pigs. In randomized order, the pigs received an infusion with 1 M sodium lactate for two hours and a control infusion with iso-osmolar and isovolumetric sodium chloride for two hours. The two infusion periods were separated by a one-hour washout period. We measured CO and pulmonary pressures hourly with a pulmonary artery catheter. A pressure-volume admittance catheter was inserted in the left ventricle to assess measures of cardiac efficiency, contractility, afterload, and preload. Hemodynamic measures as arterial blood pressure, heart rate, and mixed venous saturation (SvO2) were measured hourly as well. The study followed the principles of laboratory animal care (NIH Publication no. 85-23 revised 1985) and national and European legislations. Results Lactate levels increased by 9.9 mmol/L (95% CI 9.1 to 11.0) and CO increased by 2.0 L/min (95% CI 1.2 to 2.8) during lactate infusion as compared with the control period (figure 1). During lactate infusion, ejection fraction increased by 16.0 percentage points (95% CI 1.9 to 31.0) and heart rate by 21 bpm (95% CI 9 to 32) compared with control. Arterial elastance decreased by -1.1 mmHg/ml (95% CI -2.1 to -0.18). Lactate infusion also increased cardiac efficiency, SvO2, arterial pH, and arterial glucose concentration significantly. The infusion of lactate led to no changes in systemic arterial pressure nor pulmonary pressures including pulmonary artery wedge pressure. Also, no changes were found in left ventricle end systolic elastance (contractility). Futhermore, no change in left ventricle end-diastolic volume or -pressure (preload) were observed during lactate infusion compared with the control (figure 2). Conclusion High dose lactate infusion increased cardiac output by reducing afterload. No changes in left ventricular contractility or -preload were observed.Fig 1:Lactate concentration and COFig 2:Changes of endpoint parameters

Treatment with sacubitril/valsartan and improvement of ventricular-arterial coupling in heart failure with reduced ejection fraction

Abstract Background Treatment with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (S/V) in patients with heart failure and reduced ejection fraction (HFrEF) reduces mortality and heart failure (HF) hospitalizations. The specific hemodynamic mechanisms underlying these beneficial effects are currently unclear. Purpose This study aimed to assess the effects of S/V treatment on left ventricular (LV) end-systolic elastance (Ees), effective arterial elastance (Ea), and the ventricular-arterial coupling ratio (Ea/Ees) in patients with HFrEF using non-invasive pressure-volume analysis. Methods 117 patients with symptomatic HF and LVEF &amp;lt;40% in whom treatment with S/V was initiated were enrolled in this multicenter German prospective study. We used transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements for non-invasive pressure-volume loop analyses. Primary endpoints were changes in Ees, Ea, and Ea/Ees ratio after six months of S/V treatment. Results The mean age was 65 (±13) years and 30% were female. In 54.7% of the patients, the etiology of HF was ischemic, and 45.3% was non-ischemic. 58.4% had first HF diagnosis at baseline. 102 patients with complete clinical and echocardiographic data at baseline and after six months of follow-up were analyzed. Among those, 62% were on target dose of S/V. Six months of S/V treatment resulted in a significant increase of Ees (0.66 mmHg/ml, IQR [0.45;0.94] vs. 0.78 mmHg/ml [0.57;1.10], p=0.001) and decrease of Ea (1.76 mmHg/ml [1.48;2.13] vs. 1.62 mmHg/ml [1.36;1.96], p=0.014). Hence, the Ea/Ees ratio significantly improved (2.52 [1.88;4.05] vs. 1.93 [1.50;2.63], p&amp;lt;0.001). In addition, LV volumes and pressure improved significantly with a regression of the LV end-systolic volume (LVESV: 142 ml [115;180] vs. 96 ml [65;124]), end-diastolic volume (LVEDV: 216 ml [179;247] vs. 165 ml [132;200]) and LV end-diastolic pressure (LVEDP: 19.6 mmHg [18.2;22.4] vs. 17.8 mmHg [16.6;19.9]), p&amp;lt;0.001 respectively. The LVEF increased from a median of 33% (27;37) to 43% (36;49), p&amp;lt;0.001. NT-proBNP level decreased from (median) 1771 pg/ml [838;5211] to 724 pg/ml [300;1575] and mean 6-minute walking distance increased from 371m (±125) to 423 m (±122), p&amp;lt;0.001 respectively. The percentage of patients with NYHA class III changed from 25.6% to 5.9%. Conclusion In a 6-months treatment period, initiation of sacubitril/valsartan in patients with heart failure and reduced ejection fraction was associated with reduction of LV volumes, improved LV function, reduction in afterload and fewer heart failure symptoms. These new data indicate that beyond reverse LV remodeling, improvement of LV contractility and ventricular-arterial coupling may contribute to the favorable clinical outcomes on treatment with sacubitril/valsartan in chronic heart failure.

Right ventricular function in moderate-to-severe ventricular tricuspid regurgitation: Is there a pseudo-normalization of conventional echocardiographic parameters?

Abstract Background A reliable evaluation of right ventricular (RV) function in the presence of moderate-to-severe tricuspid regurgitation (m/s-TR) is of paramount importance for surgical or interventional risk stratification. Due to the significant systolic regurgitation of blood from the RV to the low-pressure right atrium, conventional echocardiographic parameters could appear normal and thus overestimate RV function (pseudo-normal). The aim of this study was to analyse and compare RV function in trace TR versus m/s-TR by the invasive pressure-volume-loop (PV-loop) technique, the gold standard of RV function analysis, with conventional echocardiographic indices in patients with the ventricular form of mild/no vs. m/s-TR. Methods The study was conducted in 134 patients with HFrEF in a post-hoc analysis (110 from the Magdeburg CRT Responder Trial, and 24 from a local CRT-optimization trial). Results The logistic regression analysis demonstrated that RV size (RV-end-diastolic volume, RVEDV) and RV function (measured as RV fractional area change, FAC), TAPSE, and lower fractional shortening (FS) of proximal the RV-outflow tract (RVOTprox) was closely associated with PV-loop-derived RV total afterload (pulmonary arterial elastance, Ea) and coupling of RV contractility (end-systolic RV elastance, Ees) to Ea (Ees/Ea) (all, p&amp;lt;0.001). Compared to trace TR (n=98, 73%), m/s-TR (n=36, 27%) was accompanied with significant higher total afterloads (Ea: 0.75 vs.0.41, p&amp;lt;0.001) and lower RV-PA coupling ratios (Ees/Ea, 0.4 vs. 0.79, p&amp;lt;0.001). This was associated with enlarged RVs (RVEDV: 210ml vs. 166ml), lower FAC (31% vs. 50%), TAPSE (13mm vs. 18mm), and RVOTprox (22% vs. 39%) (all p&amp;lt;0.001). For better comparability between trace TR and m/s-TR tertiles (T1-T3) of similar afterloads (Ea) were formed. The m/s-TR patients showed significant lower RV-PA coupling ratios than trace TR at the lower two Ea tertiles T1 (p=0.034) and T2 (p&amp;lt;0.001). At Ea T3 the difference was no longer significant (p=0.055). The hemodynamic data are mirrored by significant lower FACs, FS RVOTprox, and TAPSE at T1 and T2 (all p&amp;lt;0.05), and a nonsignificant difference at T3 in m/s-TR. In conclusion: In our cohort of HFrEF patients, echocardiographic RV function reflects very closely the hemodynamic coupling efficiency of RV contractility (Ees) to afterload (Ea) and seems independent from the extent of TR. We found no evidence for pseudo-normal or overestimated echocardiographic RV function in m/s-TR.

Abstract 13719: Minimal and Delayed Age-Related Increase of Arterial Stiffness Among Tsimane Forager-Horticulturalists

Background: Tsimane forager-farmers of the Bolivian Amazon exhibit a distinct trajectory of vascular aging, characterized by low age-related increases in BP, the lowest levels of coronary calcification ever reported, and robust VO 2 max. However, the prevalence of arterial stiffness (ArSt) in this population and its association with age and other cardiovascular risk factors are unknown. Methods: Large artery elasticity (LAE) and small artery elasticity (SAE) were measured among 491 Tsimane adults (mean age 55.3±13.0 y, 55% female) using HDI CR-2000 (Eagan, MN). Carotid-femoral pulse wave velocity (cfPWV) was assessed among 89 Tsimane (mean age 53.1±15.7 y, 54% female) using the foot-to-foot method with ECG and carotid/femoral pulse wave data. Results: Compared to previous studies from diverse urban populations, Tsimane show lower indices of ArSt: higher LAE (mean 22.79±12.21 ml/mmHg·10) and SAE (mean 7.57±4.04 ml/mmHg·100), and lower cfPWV (mean 6.34±2.1 m/s). LAE and SAE are 73% and 57% higher for Tsimane men, and 70% and 86% higher for Tsimane women, compared to age-matched US MESA adults. Tsimane demonstrate lower LAE and SAE with age, while higher cfPWV was only evident among Tsimane over 70 years (β=2.26±0.71, P =0.001; reference &lt;40 y). Hypertension is rare in this population, but was associated with having higher ArSt. Conclusion: Tsimane forager-farmers have substantially lower levels of ArSt and fewer age-related differences in ArSt compared to more urbanized and sedentary populations. The minimal and delayed age-related increase of arterial stiffness might contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimane.

Abstract 11994: Lithotripsy-Assisted Transcatheter Aortic Valve Implantation: An Emerging Approach to Vascular Access Issues in Severe Peripheral Arterial Disease

Introduction: Advances in minimally invasive valvular interventions like transcatheter aortic valve implantation (TAVI) allow for treatment of an increasingly older population. Severe calcific iliofemoral peripheral arterial disease (PAD) can preclude large sheath introduction necessary in TAVI. Conventional peripheral angioplasty has limited efficacy in these situations given its high-pressure dilation, which increases the risk of vascular complications. Intravascular shockwave lithotripsy (IVL) for PAD is an emerging and safe alternative for vascular access. Case Description: A 90-year-old man with severe symptomatic aortic stenosis (AS), coronary artery disease (CAD) status-post CABG and extensive PAD was referred for TAVI following balloon aortic valvuloplasty. Transthoracic echocardiogram showed severe, low-flow, low-gradient AS despite recent balloon aortic valvuloplasty. Abdominal imaging showed severe atherosclerosis and calcification of the bilateral common and external iliac arteries. Prior to TAVI, peripheral angiogram was performed, followed by IVL for a total of nine runs, each for fifteen seconds with a 7x60mm balloon to the right iliac and femoral arteries. Then, the right femoral groin sheath was upsized from six to eighteen French, followed by deployment of a 29mm Medtronic Evolute Pro+ self-expanding bioprosthetic aortic valve. Following successful TAVI, the patient was discharged home on aspirin and clopidogrel. Conclusion: IVL utilizes pulsatile mechanical shockwaves to modify plaque burden without altering arterial elasticity or structural integrity, which greatly reduces the risk for vascular complications in severely calcified arteries. The DISRUPT-PAD-III trial showed IVL was superior to percutaneous transluminal angioplasty with fewer complications in patients with calcified PAD. Therefore, IVL can be a safe alternative approach for PAD limiting vascular access in percutaneous valvular interventions.

Abstract 14318: Right Ventriculo- Arterial Coupling Assessment by High-Fidelity Hemodynamic Measurements in Patients Undergoing Left Ventricular Assist Device Implantation

Background: The changes in RV function after LVAD placement are not fully understood. RV- PA coupling, defined as the ratio of RV end-systolic to arterial elastances (E ES /E A ), offers unique insight into the cardiopulmonary unit and opportunity to address these knowledge gaps. We present early results from our study investigating RV adaptive changes after LVAD implantation by intraoperative placement of RV conductance catheters. Methods: Conductance catheter, echocardiographic, and hemodynamic data were gathered starting on the day of surgery. We used a 7Fr high-fidelity RV conductance catheter delivered through a 9Fr central venous sheath. P-V loop parameters were obtained before skin incision and after chest closure. Single- beat methods were used for E ES /E A determination. Early RVF was defined according to INTERMACS criteria. Intraoperative pre- and post-implantation echocardiographic and hemodynamic parameters were compared. Results: We present data on the first 14 patients who underwent successful placement of the RV conductance catheter. Moderate or severe RVF occurred in 3 patients (21.4%). Data are presented in the table. While overall E Es (1.2 vs 1.3, p=0.785), E A (1.1 vs 1.3, p=0.154), and RV-PA coupling (E ES /E A ratio 1.1 vs 1.0, p=0.129 ) remained unchanged, several patients underwent dramatic changes, either increase or decrease, in E ES and E A (Figure). Measures of energetic expense, such as stroke work ( SW, correlate of myocardial energy transferred) and pressure-volume area (PVA, correlate of myocardial oxygen consumption) significantly decreased after LVAD implantation. Conclusions: We have shown that RV function assessment using conductance catheters and 3D echocardiography is feasible and able to identify individual responses in RV-PA coupling after LVAD implantation. Continued accrual of data will help identify different phenotypes of RV adaptation and establish a cut-off level of RV-PA uncoupling at which RVF occurs.

Wall Properties of Elastic and Muscular Arteries in Children and Adolescents at Increased Cardiovascular Risk.

Pulse wave velocity (PWV) assessment represents a simple method to estimate arterial distensibility. At present, carotid-femoral PWV (cf-PWV) is considered the gold standard method in the non-invasive evaluation of the elastic properties of the aorta. On the other hand, the mechanical properties of muscular arteries can be evaluated on the axillo-brachial-radia axis by estimating the carotid-radial PWV (cr-PWV). While a number of studies have addressed these issues in adults, limited information is available on the respective features of cf-PWV and cr-PWV and on their modulating factors in children and adolescents at increased cardiovascular risk. The mechanical properties of the predominantly elastic (aorta) and muscular (axillo-brachial-radial axis) arteries were evaluated in a pediatric population characterized by either elevated blood pressure (BP) or excess body weight, and the main factors affecting cf-PWV and cr-PWV values in these individuals were investigated. 443 children and adolescents (median age 11.5 years, 43.3% females) were enrolled; 25% had BP values >90th percentile and 81% were excess weight. The cf-PWV values were significantly lower than the cr-PWV values: median (Q1-Q3) = 4.8 m/s (4.3-5.5) and 5.8 m/s (5.0-6.5), respectively (p < 0.001). The pubertal development (p < 0.03), systolic BP and diastolic BP z-scores (p = 0.002), heart rate (p < 0.001), and waist-to-height ratio (p < 0.005) were significantly associated with cf-PWV values. No significant association was found between BMI z-score and cf-PWV. Predictors of high cf-PWV (>95th percentile) were the heart rate (OR 1.07, 95%CI 1.04-1.10, p < 0.001) and waist-to-height ratio (OR 1.06, 95%CI 1.0-1.13, p = 0.04). The variables significantly related with cr-PWV values were diastolic BP z-score (p = 0.001), heart rate (p < 0.01), and HOMA index (p < 0.02). No significant association was found between the cr-PWV and BMI z-score or waist-to-height ratio. Systolic and diastolic BP values and central obesity are associated with aortic stiffness in a population of children and adolescents at increased cardiovascular risk. In contrast, diastolic BP, heart rate, and levels of insulin resistance appear to be related to distensibility of the upper limb vascular district.