Mean Aortic Pressure Research Articles

In vitro Doppler versus catheter transvalvular pressure gradients in balloon-expandable versus self-expanding transcatheter aortic valves.

The objective of this in vitro study was to compare Doppler versus catheter transvalvular pressure gradients (TPG) in third generations balloon-expandable (BE) versus self-expanding (SE) transcatheter heart valves (THV). TPG is a key parameter to assess and follow valve hemodynamic function following transcatheter aortic valve implantation (TAVI). It remains uncertain and debated whether, and to which extent, TPGs differ according to the type of THV, that is, BE versus SE and to the method used for TPG measurement, that is, Doppler echocardiography versus cardiac catheterization. The CoreValve EVOLUT PRO 26 mm and the SAPIEN 3 23 mm THVs were tested in a left heart simulator using a 21 mm aortic annulus under following conditions: heart rate: 70 bpm, mean aortic pressure: 100 mmHg, stroke volume: 30, 70 and 100 ml. Mean TPGs were measured by continuous-wave Doppler and by micro-tip pressure catheters positioned in the left ventricle and at 50 mm downstream to the tip of the THV leaflets. Doppler TPGs (9.5 ± 3.9 mmHg) were on average 40.5 ± 13.9% higher (p < 0.001) than catheter TPGs (6.3 ± 3.4 mmHg). Both Doppler and catheter TPGs were lower (p=0.003) in the SE versus BE THVs (Doppler: 8.7 ± 3.5 vs. 10.7 ± 4.6; catheter: 5.0 ± 1.7 mmHg vs. 7.1 ± 2.2). The Doppler versus catheter difference in TPG increased with the higher flow conditions. The Doppler versus catheter difference in TPG was similar in BE versus SE THVs (3.6 ± 1.1 vs. 3.7 ± 1.4 mmHg or 42 ± 9 vs. 47 ± 9%; p=0.58) overall and in each flow conditions. The Doppler TPGs are, on average, 40% higher than the catheter TPGs for both BE and SE THVs. The SE THV had lower Doppler and catheter TPGs compared to the BE THV, at normal and high flow states. The absolute and percent differences between Doppler versus catheter TPGs were similar in BE versus SE THVs.

NATURAL HISTORY OF MITRAL ANNULUS CALCIFICATION AND CALCIFIC MITRAL VALVE DISEASE

<h3>BACKGROUND</h3> Mitral annular calcification (MAC) is a common finding, but the natural history and risk for developing calcific mitral valve disease (CMVD) have been poorly defined. We sought to evaluate the progression rate of MAC and of the development of CMVD. <h3>METHODS AND RESULTS</h3> Patients with at least mild MAC and paired echocardiograms at least one year apart between 2005 and 2019 were included. Progression rates from mild/moderate MAC to severe MAC and to CMVD (defined as severe MAC and significant mitral stenosis and/or regurgitation) were assessed, along with potential associations with sex and aortic valve stenosis (AS) progression. A total of 11,605 patients (73±10 years, 51% male) with MAC (78% mild, 17% moderate, 5% severe) were included and had a follow up echocardiogram at 4.2±2.7 years. In patients with mild/moderate MAC on their initial echocardiogram, the incidence of severe MAC at 10 years was 33%. The incidence was higher in females than in males (41% vs. 24%, P < 0.001, HR=1.3, P < 0.001) and in patients with moderate vs. mild MAC (71% vs. 22%, P < 0.001, HR=6.1, P < 0.001, see Figure 1). The overall incidence of CMVD at 10 years was 10% (4%, 23% and 60% in patients with mild, moderate, and severe MAC, respectively) and was predicted by female sex (15% vs. 5%, P < 0.0001), even after adjustment for MAC severity (HR=1.9, P < 0.001, see Figure 2). Patients who progressed to severe MAC had larger increases in aortic valve mean pressure gradient (AV MPG) (+4.1±4.5 vs. +3.3±3.6 mmHg/year, P < 0.001) that persisted after adjustment for age, sex, and baseline AV MPG. <h3>CONCLUSION</h3> In this large patient cohort with MAC, progression to severe MAC is common and frequently results in CMVD. Female sex was associated with higher progression rates and an association between MAC and AS progression was observed. MAC and CMVD are expected to dramatically increase as the population ages and there is an urgent need to better understand the pathophysiology of MAC in order to develop effective preventative medical therapies.

Myocardial Perfusion in Hypoplastic Left Heart Syndrome

The status of the systemic right ventricular coronary microcirculation in hypoplastic left heart syndrome (HLHS) is largely unknown. It is presumed that the systemic right ventricle's coronary microcirculation exhibits unique pathophysiological characteristics of HLHS in Fontan circulation. The present study sought to quantify myocardial blood flow by cardiac magnetic resonance imaging and evaluate the determinants of microvascular coronary dysfunction and myocardial ischemia in HLHS. One hundred nineteen HLHS patients (median age, 4.80 years) and 34 healthy volunteers (median age, 5.50 years) underwent follow-up cardiac magnetic resonance imaging ≈1.8 years after total cavopulmonary connection. Right ventricle volumes and function, myocardial perfusion, diffuse fibrosis, and late gadolinium enhancement were assessed in 4 anatomic HLHS subtypes. Myocardial blood flow (MBF) was quantified at rest and during adenosine-induced hyperemia. Coronary conductance was estimated from MBF at rest and catheter-based measurements of mean aortic pressure (n=99). Hyperemic MBF in the systemic ventricle was lower in HLHS compared with controls (1.89±0.57 versus 2.70±0.84 mL/g per min; P<0.001), while MBF at rest normalized by the rate-pressure product, was similar (1.25±0.36 versus 1.19±0.33; P=0.446). Independent risk factors for a reduced hyperemic MBF were an HLHS subtype with mitral stenosis and aortic atresia (P=0.017), late gadolinium enhancement (P=0.042), right ventricular diastolic dysfunction (P=0.005), and increasing age at total cavopulmonary connection (P=0.022). The coronary conductance correlated negatively with systemic blood oxygen saturation (r, -0.29; P=0.02). The frequency of late gadolinium enhancement increased with age at total cavopulmonary connection (P=0.014). The coronary microcirculation of the systemic ventricle in young HLHS patients shows significant differences compared with controls. These hypothesis-generating findings on HLHS-specific risk factors for microvascular dysfunction suggest a potential benefit from early relief of frank cyanosis by total cavopulmonary connection.

Comparison of Echocardiographic Variables in Patients With Severe Aortic Stenosis and Preserved Ejection Fraction Grouped by Flow and Gradient

The pathophysiology of severe aortic stenosis (AS) is complex with vascular, valvular, and myocardial components. To better define this process, we compared echocardiographic and clinical variables in patients with severe AS and preserved EF according to flow and gradient. We retrospectively studied the clinical and echocardiographic data of 287 patients (mean age 76 ± 11 years, 57% men) from 2012 to 2017 with severe AS (indexed aortic valve area <0.6 cm2/m2) and preserved ejection fraction (>50%). Patients were divided into 4 groups based on flow (stroke volume index < or ≥35 ml/m2) and mean aortic pressure gradient (< or ≥40 mm Hg): normal flow, high gradient (NFHG), normal flow, low gradient (NFLG), low flow, high gradient (LFHG) and low flow, low gradient (LFLG). Among patients with severe AS, 23% had NFHG, 44% had NFLG, 10% had LFHG, and 23% had LFLG. Only diabetes was marginally significantly different among the clinical variables. Aortic valve area index was largest in NFLG and smallest in LFHG (p < 0.001 for pairwise comparisons). Valvuloarterial impedance was highest in LFHG (p < 0.01 for pairwise comparisons). Systemic arterial compliance was lower and systemic vascular resistance was higher in low flow compared with normal flow groups. In conclusion, LFHG had the smallest valve area index along with markers of increased vascular resistance combined with high gradients, which suggests a unique pathophysiology in this group of severe AS patients with preserved EF.

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes

ObjectivesAdenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. MethodsTwenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. ResultsMean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44–0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm−1.sec−1 vs 4.2 ± 1.7 mmHg.cm−1.sec−1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all). ConclusionsIn patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Controlling the flow balance: In vitro characterization of a pulsatile total artificial heart in preload and afterload sensitivity.

The objective of this study is to identify the preload and afterload sensitivity of the ReinHeart TAH 2.0. For adequate left-right flow balance, the concept of a reduced right stroke volume (by about 10%) and active adaption of the right diastole duration are evaluated concerning the controllability of the flow balance. This study used an active mock circulation loop to test a wide range of preload and afterload conditions. Preload sensitivity was tested at atrial pressures (APs) between 4 and 20mmHg. Left afterload was varied in a range of 60-140mmHg mean aortic pressure (MAP), right afterload was simulated between 15 and 40mmHg. Four scenarios were developed to verify that the flow difference fully covers the defined target range of 0-1.5L/min. Although a positive correlation between inlet pressure and flow is identified for the right pump chamber, the left pump chamber already fills completely at an inlet pressure of 8-10mmHg. With increasing afterload, both the left and right flow decrease. A positive flow balance (left flow exceeds right flow) is achieved over the full range of tested afterloads. At high APs, the flow difference is limited to a maximum of 0.7L/min. The controllability of flow balance was successfully evaluated in four scenarios, revealing that a positive flow difference can be achieved over the full range of MAPs. Under physiological test conditions, the linear relationship between flow and heart rate was confirmed, ensuring good controllability of the TAH.

Effects of Add-On Left Ventricular Assist Device to Extracorporeal Membrane Oxygenation During Refractory Cardiac Arrest in a Porcine Model.

This study evaluated the effects of extracorporeal membrane oxygenation (ECMO) in combination with a percutaneous adjunctive left ventricular assist device (LVAD) in a porcine model during 60 minutes of refractory cardiac arrest (CA). Twenty-four anesthetized swine were randomly allocated into three groups given different modes of circulatory assist: group 1: ECMO 72 ml/kg/min and LVAD; group 2: ECMO 36 ml/kg/min and LVAD; and group 3: ECMO 72 ml/kg/min. During CA and extracorporeal cardiopulmonary resuscitation (ECPR), mean left ventricular pressure (mLVP) was lower in group 1 (p = 0.013) and in group 2 (p = 0.003) versus group 3. Mean aortic pressure (mAP) and coronary perfusion pressure (CPP) were higher in group 1 compared with the other groups. In group 3, mean pulmonary artery flow (mPAf) was lower versus group 1 (p = 0.003) and group 2 (p = 0.039). If the return of spontaneous circulation (ROSC) was achieved after defibrillation, up to 180 minutes of unsupported observation followed. All subjects in groups 1 and 3, and 5 subjects in group 2 had ROSC. All subjects in group 1, five in group 2 and four in group 3 had sustained cardiac function after 3 hours of spontaneous circulation. Subjects that did not achieve ROSC or maintained cardiac function post-ROSC had lower mAP (p < 0.001), CPP (p = 0.002), and mPAf (p = 0.004) during CA and ECPR. Add-on LVAD may improve hemodynamics compared with ECMO alone during refractory CA but could not substitute reduced ECMO flow. Increased mAP and CPP could be related to ROSC rate and sustained cardiac function. Increased mLVP was related to poor post-ROSC cardiac function.

Extracardiac coronary steal induced by upper limb hyperemia: a feature of internal mammary artery arteriogenesis.

Function of naturally existing internal mammary artery (IMA)-to-coronary artery anastomoses has been shown by augmented blood supply to the coronary collateral circulation in response to IMA occlusion. Theoretically, this beneficial functional connection is invertible and can be linked to coronary steal, the verification of whose hypothesis would provide alternate proof to the mentioned functional evidence. This was an observational study including 40 patients with chronic coronary syndrome, distal IMA occlusion, and upper limb hyperemia (verum group), and 40 propensity score matched controls (placebo group) without IMA occlusion or hyperemia. Primary study end point was the intergroup difference and temporal development in coronary collateral function (i.e., collateral flow index; CFI) as obtained at 30, 45, and 60 s following a proximal coronary artery balloon occlusion. CFI is the ratio between simultaneous mean coronary occlusive pressure divided by mean aortic pressure both subtracted by central venous pressure. To provoke a steal phenomenon, upper limb hyperemia was induced by upper arm blood pressure cuff deflation following a 5-min suprasystolic inflation ipsilateral to the sensor-wired coronary artery with release immediately after the first CFI measurement. Between the first and the second CFI measurement, CFI change (i.e., CFI@45s - CFI@30s) was absent in the verum group whereas there was CFI recruitment in the placebo group: 0.000 ± 0.023 and +0.009 ± 0.013, respectively; P = 0.032. Among patients with artificial distal IMA occlusion, induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal as expressed by temporarily absent collateral recruitment as it normally takes place without upper limb hyperemia.NEW & NOTEWORTHY Induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal among patients with artificial distal internal mammary artery occlusion. Coronary steal via the occluded internal mammary arteries serves as alternate proof of concept of the already existing evidence of their functional extracoronary collateral supply.

Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.

Clinical outcomes after implantation of a sutureless aortic bioprosthesis with concomitant mitral valve surgery: the SURE-AVR registry

BackgroundEarly treatment of aortic valve stenosis is recommended in eligible symptomatic patients with severe aortic valve stenosis who would otherwise have a poor prognosis. The sutureless aortic valve bioprosthesis offers an alternative to standard aortic valve replacement with a sutured valve, but limited data are available in patients who have undergone multiple valve procedures involving the new, sutureless technology. We sought to investigate outcomes in high operative risk patients with previous or concomitant valve surgery who were implanted with a sutureless valve.MethodsSURE-AVR is an ongoing, prospective, multinational registry of patients undergoing aortic valve replacement. In-hospital and post-discharge outcomes up to 5 years were collected.ResultsThe study population comprised 78 patients (mean ± SD: age 73.6 ± 7.6 years, logistic EuroSCORE 18.0 ± 17.5) enrolled at 13 sites who presented for concomitant or previous mitral valve repair (n = 45) or replacement (n = 33), with or without additional concomitant procedures, and were implanted with a sutureless valve. Mean ± SD overall aortic cross-clamp time was 109 ± 41 min and cardiopulmonary bypass time was 152 ± 49 min. Mean ± SD aortic pressure gradients decreased from 37.6 ± 17.7 mmHg preoperatively to 13.0 ± 5.7 mmHg at hospital discharge, and peak aortic pressure gradient from 61.5 ± 28.7 to 23.4 ± 10.6 mmHg. Early events included 1 death, 1 transient ischaemic attack, and 1 bleed (all 1.3%); a permanent pacemaker implantation was required in 6 patients (7.7%), and 2 reoperations (not valve related) (2.6%) took place. Over a median follow-up of 55.5 months (Q1 13.4, Q3 68.6), 12 patients died (6 cardiovascular and 6 non-cardiovascular, both 2.1% per patient-year). Five-year survival was 81.3%. Late paravalvular leak occurred in 2 patients (0.7% per patient-year) and permanent pacemaker implantation was required in 3 patients (0.1% per patient-year). There was no apparent rise in mean or peak aortic pressure gradient over the study.ConclusionsThese results suggest that the sutureless implant is a technically feasible procedure during mitral surgery and is associated with good clinical outcomes.

Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects

BackgroundElevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial.MethodsWe investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19–73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis.ResultsThe mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (β = 0.168, p < 0.001, R2 of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes.ConclusionsPUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.

Early and mid-term results of transcatheter aortic valve implantation and valve durability assessment.

This study aimed to evaluate the early and mid-term outcomes of transcatheter aortic valve implantation (TAVI) and to assess valve durability. A total of 146 consecutive patients who underwent TAVI for severe aortic stenosis between October 2013 and August 2018 were retrospectively reviewed. All patients (mean age, 84 ± 6years; age range 53-98years; 42 males [28.7%]) had multiple comorbidities, with a mean logistic EuroSCORE of 30.9 ± 17.4%. Eighteen patients (12.3%) were aged 90years or over. Five in-hospital deaths (3.4%) occurred, and 36 patients (24.7%) experienced major TAVI-related complications. With the transfemoral approach, 10 patients had major vascular complications, which mostly occurred with first-generation devices (n = 9) but less commonly with new-generation low-profile devices (P = 0.0078). During a follow-up period of 580 ± 450 (11-1738) days, 29 late deaths occurred. The survival rate was 86.0%, 78.0%, and 61.7% at 1, 2, and 3years, respectively. Multivariate Cox hazard regression analysis revealed that more-than-moderate tricuspid regurgitation was the only independent risk factor for late deaths due to any cause (hazard ratio, 3.145; 95% confidence interval, 1.129-8.762; P = 0.0283). No statistically significant differences between post-TAVI before discharge from the hospital and at 4years after TAVI were observed with respect to aortic valve area (1.76 ± 0.49cm2 vs. 1.64 ± 0.38cm2; P = 0.1871) and mean pressure gradient (10.0 ± 4.6mmHg vs. 7.9 ± 3.3mmHg; P = 0.5032). TAVI was a feasible method with acceptable early and mid-term outcomes and valve durability for at least 4years in poor-risk patients. Further close follow-up is essential to evaluate late outcomes and valve durability.

NON-INVASIVE ASSESSMENT OF CENTRAL AORTIC PRESSURE, AORTIC FLOW AND VASCULAR LOAD IN PATIENTS WITH AORTIC STENOSIS BEFORE AND AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT

Objective: The left ventricle (LV) faces a dual afterload in patients with aortic stenosis (AS), both from the narrowed valve and age-related arterial stiffening. Variability in indices of AS severity assessment suggests an inter-relationship of the valvular pressure gradient on systemic arterial pressure and flow. Our study aims to evaluate the dynamic vascular load (VL) non-invasively in AS patients before and after transcatheter aortic valve replacement (TAVR) using the approach of simultaneous cardiac magnetic resonance (CMR) and radial applanation tonometry (AT). Design and method: Ascending aortic pressure, flow and VL were measured in 3 patients at baseline and post-TAVR using a previously reported simultaneous CMR/AT technique. CMR provided aortic flow, and radial AT waves were converted offline to aortic pressure using SphygmoCor 8.1 (AtCor Medical) and calibrated using brachial cuff values. VL was determined as the relationship of derived aortic pressure to CMR aortic flow velocity, by calculating the average modulus of pressure divided by flow. Following the acquisition of post TAVR data, 300 micrograms of sublingual nitroglycerine (GTN) was introduced to investigate the effect on changing vascular load. Results: At 38 ± 3 days post TAVR, mean aortic pressure (MP) and mean systolic flow (MF) both increased (100 ± 17 pre, 109 ± 12 post, mmHg; 178 ± 44 pre, 230 ± 74 post, ml/s). Following GTN administration, MP (95 ± 3 mmHg) decreased but not MF (228 ± 57 ml/s) – see figure. The steady state systemic vascular resistance (SVR) reduced post TAVR (22501 ± 5929 pre, 20484 ± 6232 post, dynes.s/cm3), but not VL (1082 ± 219 pre, 1111 ± 483 post, dynes.s/cm3). Conversely, GTN administration significantly reduced VL (838 ± 295 dynes.s/cm3) with little effect on SVR (19313 ± 5631 dynes.s/cm3). Conclusions: Our study demonstrates that our novel technique can be reliably replicated in patients to evaluate the changes to aortic pressure, flow and VL before and after TAVR. VL appears to be a dynamic measurement of vascular stiffness independent of AS and may prove to be a useful measure to predict haemodynamic responses and ventriculo-arterial coupling in AS patients post TAVR. Larger longitudinal cohort studies are warranted.

The relationship between calcific severe aortic stenosis and systemic immune‐inflammation index

Calcific aortic stenosis (AS) is a common valvular disease especially in elderly population. Inflammation plays significant role in the pathophysiological mechanism. Systemic immune-inflammation index (SII) is a novel marker of immune system and inflammation that includes neutrophil, lymphocyte, and platelet cell counts. The aim of this study was to investigate the predictive value of SII in calcific severe AS. Severe calcific AS patients were categorized into two groups: High flow-high gradient (HFHG) AS (n=289) and low flow-low gradient AS (n=79). Control group included 273 patients with similar clinical and demographic characteristics but without AS. SII was calculated as absolute platelet count×absolute neutrophil count/absolute lymphocyte count. SII levels were 525±188, 835±402, and 784±348 in control, HFHG AS, and LFLG AS groups, respectively (P<.001). Correlation analyses revealed significant and positive correlation between SII and mean aortic transvalvular pressure gradient (r=.342, P<.001), and negative and significant correlation between SII and AVA (r=-.461, P<.001). Multivariate analysis performed in separate models demonstrated sex, CAD, LDL, and SII levels (Odds ratio [OR]: 1.004, 95 CI%:1.003-1.004) as independent predictors of severe AS in Model 1. According to Model 2, sex, CAD, LDL, and high SII (>661) (OR:5.78, 95 CI%:3.93-4.89) remained as independent predictors of severe AS. SII levels can be useful to predict severe calcific AS patients and significantly correlate with AVA and mean aortic transvalvular pressure gradient.

A randomized and blinded trial of inhaled nitric oxide in a piglet model of pediatric cardiopulmonary resuscitation

AimInhaled nitric oxide (iNO) during cardiopulmonary resuscitation (CPR) improved systemic hemodynamics and outcomes in a preclinical model of adult in-hospital cardiac arrest (IHCA) and may also have a neuroprotective role following cardiac arrest. The primary objectives of this study were to determine if iNO during CPR would improve cerebral hemodynamics and mitochondrial function in a pediatric model of lipopolysaccharide-induced shock-associated IHCA. MethodsAfter lipopolysaccharide infusion and ventricular fibrillation induction, 20 1-month-old piglets received hemodynamic-directed CPR and were randomized to blinded treatment with or without iNO (80 ppm) during and after CPR. Defibrillation attempts began at 10 min with a 20-min maximum CPR duration. Cerebral tissue from animals surviving 1-h post-arrest underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and immunohistochemical analyses to assess neuropathology. ResultsDuring CPR, the iNO group had higher mean aortic pressure (41.6 ± 2.0 vs. 36.0 ± 1.4 mmHg; p = 0.005); diastolic BP (32.4 ± 2.4 vs. 27.1 ± 1.7 mmHg; p = 0.03); cerebral perfusion pressure (25.0 ± 2.6 vs. 19.1 ± 1.8 mmHg; p = 0.02); and cerebral blood flow relative to baseline (rCBF: 243.2 ± 54.1 vs. 115.5 ± 37.2%; p = 0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O2/s mg; p = 0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O2/s mg; p = 0.02). There were no other differences in mitochondrial respiration or brain injury between groups. ConclusionsTreatment with iNO during CPR resulted in superior systemic hemodynamics, rCBF, and cerebral mitochondrial Complex I respiration in this pediatric cardiac arrest model.

Development of the Left Atrial Assist Device for Patients with Heart Failure with Preserved Ejection Fraction: First In Vivo Results

<h3>Purpose</h3> The Left Atrial Assist Device (LAAD) is a novel device in development for mechanical circulatory assistance in patients who have heart failure with preserved ejection fraction (HFpEF). The device is implantable in the mitral position and delivers blood from the left atrium to the left ventricle. We report our results of the first LAAD <i>in vivo</i> implantation to assess the operational performance. <h3>Methods</h3> The LAAD was implanted in calves (<i>n</i>=4; mean weight 78.9 kg) using cardiopulmonary bypass (CPB) support through a left atrial incision. Horizontal mattress sutures were placed circumferentially around the mitral annulus and through the LAAD sewing ring (diameter 29 mm, Fig. 1a). Various pump-operating conditions, including mean pump speeds ranging from 3,600 to 6,000 rpm, were evaluated after the CPB was weaned, and the hemodynamics for each pump setting were recorded. <h3>Results</h3> The LAAD responded to all control inputs and ran as expected during the experiment. The cardiac output and mean aortic pressure increased (from 5.3 to 6.0 L/min, and from 69 to 77 mm Hg, respectively) by increasing the pump speed from 3,600 to 4,400 rpm, while the mean left atrial pressure decreased (from 15.1 to 8.3 mm Hg). These parameters stayed the same at pump speeds of 4,400 to 5,200 rpm. The left ventricular end-diastolic pressure, central venous pressure and heart rate remained stable at speeds ranging from 3,600 to 5,200 rpm. Suction events were occasionally observed at speeds over 4,400 rpm, mainly because of the small size of the left atrium. The epicardial echocardiography showed good positioning of the LAADs, with no evidence of obstruction of the left ventricular outflow tracts (Fig. 1b). <h3>Conclusion</h3> The implantation of the LAADs in calves was successful, and the pump showed intended improvement of the hemodynamics in the normal calf hearts. Additional studies are underway to evaluate the pump performance under diastolic heart failure conditions.

Coronary angiography-derived contrast fractional flow reserve.

Based on coronary angiography and mean aortic pressure, a specially designed computational flow dynamics (CFD) method is proposed to determine contrast fractional flow reserve (cFFR) without using invasive pressure wire. This substudy assessed diagnostic performance of coronary angiography-derived cFFR in catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR). Patients with diagnosis of stable angina pectoris or unstable angina pectoris were enrolled in six centers. Wire-based FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline angiography-derived cFFR was computed in blinded fashion against the wire-based FFR and caFFR at an independent core laboratory. A total of 330 patients were enrolled to fulfill inclusion/exclusion criteria from June 26 to December 18, 2018. Offline angiography-derived cFFR and wire-based FFR results were compared in 328 interrogated vessels. The statistical analysis showed the highest diagnostic accuracy of 89.0 and 86.6% for angiography-derived cFFR with a cutoff value of 0.94 and 0.93 against the wire-based FFR with a cutoff value of 0.80 and 0.75, respectively. The corresponding sensitivity and specificity were 92.2 and 87.3% for the cutoff value of 0.94 and 80.0 and 88.4% for the cutoff value of 0.93, which are similar to those against the caFFR. The receiver-operating curve has area under the curve of 0.951 and 0.972 for the wire-based FFR with the cutoff value of 0.80 and 0.75, respectively. Coronary angiography-derived cFFR showed higher accuracy, sensitivity, and specificity against wired-based FFR and caFFR. Hence, angiography-derived cFFR could enhance the hemodynamic assessment of coronary lesions.

Left atrial functional assessment and mortality in patients with severe aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction: Aortic valve stenosis (AS) is the most common primary valvular heart disease leading to surgical or percutaneous aortic valve replacement (AVR) in Europe. Both symptoms and systolic dysfunction can appear late in the course of the disease, being often synonym of irreversible damage to the myocardium when found. Thus, there is a necessity to find other sensitive markers present at an earlier stage of the disease. Purpose Our primary aim is to clarify the relationship between LA function measured at severe AS diagnosis (evaluated by means of volumetric assessment) and all-cause mortality during follow-up. Methods We retrospectively evaluated patients diagnosed with severe AS for the first time at our echocardiography laboratory. We evaluated all 3 left atrial (LA) functional phases (reservoir, conduit and pump) by measuring LA volumes at different timings of cardiac cycle. Treatment strategy was decided according to heart team consensus and own patient decision. We divided patients into groups according to terciles of LA reservoir, conduit and pump function. Primary outcome was defined by the occurrence of all-cause mortality during follow-up. Results After exclusion criteria, a total of 451 patients were included in the analysis (aged 74 ±11years, 54% male) and were followed during a median period of 73 months (interquartile range 44.5). A total of 55.8% of patients underwent AVR and 45,5% of patients registered the primary outcome. Left atrial emptying fraction (LAEF) was the best LA functional parameter in discriminating primary outcome (AUC 0.840, p &amp;lt; 0.001), even when compared to left ventricular ejection fraction, aortic valve area, aortic mean pressure gradient and aortic Vmax. Patients in the lower tercile of LAEF were older, had greater comorbidities, had greater AS severity, with greater degree of diastolic disfunction. After adjustment for clinical and demographic variables, cumulative survival of patients with LAEF &amp;lt;37% and LAEF 37 to 53% relative to patients with LAEF ≥54% remained significantly lower (adjusted HR 19.04, 95% CI 8.30-43.67, P &amp;lt; 0.001 and adjusted HR 4.09, 95% CI 1.85-9.06, P = 0.001). Survival was also higher in patients with LAEF 37 to 53% when compared to patients with LAEF &amp;lt;37% (adjusted HR 0.22, 95% CI 0.13-0.37, P &amp;lt; 0.001). All associations remained true after adjustment for AVR (LAEF &amp;lt;37% versus LAEF 37 to 53% and LAEF ≥54%, respectively, adjusted HR 3.97, 95% CI 1.80-8.78, P = 0.001 and adjusted HR 13.95, 95% CI 5.98-32.54, P &amp;lt; 0.001, respectively) Conclusion(s) In patients with a first diagnosis of severe AS in hospital setting, LA function assessed by volumetric parameters is an independent predictor of all-cause mortality. Compared to classical severity parameters, different LA functional parameters were found to be more potent predictors of death. These data can be useful in clinical practice for risk stratification and therefore for decision of timing for AVR. Abstract Figure. Survival of patients stratified by group

Influence of different physiological hemodynamics on fractional flow reserve values in the left coronary artery and right coronary artery.

Although the left coronary artery (LCA) has a flow profile in that most blood flow occurs during diastole rather than systole, the right coronary artery (RCA) has a flow pattern that is less diastolic dominant. This study assessed whether coronary pressure waveforms distal to stenoses with the same fractional flow reserve (FFR) was the same between the LCA and RCA. A total of 347 vessels from 318 patients who underwent FFR measurements were included. Conventional FFR was calculated as the ratio of the mean coronary distal pressure (Pd) to the mean aortic pressure (Pa) at maximal hyperemia. The pressure drop ratios in systole (PDRsystole) and diastole (PDRdiastole) were calculated as the sum of (Pa minus Pd) divided by the sum of Pa at the intracoronary diastolic and systolic pressure phases, respectively. Analysis of covariance of the regression line of correlation between conventional FFR and PDRsystole revealed that the slope was significantly greater in the RCA than in the left anterior descending artery (LAD) and left circumflex artery (LCX) (-0.765, -0.578, and -0.589, p < 0.001). On the other hand, the regression line of correlation between conventional FFR and PDRdiastole found that the slope was significantly greater in the LAD and LCX than in the RCA (-1.349, -1.318, and -1.223, p < 0.001). The pressure waveform distal to the stenosis differs between the LCA and RCA. In the LCA, the decrease in diastolic pressure mainly contributed to the drop in FFR, whereas in the RCA, it was the decrease in systolic pressure.

The nonpharmacological sequence method provides a reliable evaluation of baroreflex sensitivity in fish.

The most commonly used technique to study the barostatic regulation of blood pressure in ectothermic vertebrates consists of determining the heart rate response to pharmacological manipulations of blood pressure, the so-called "Oxford method."Although well established, the Oxford method has some important limitations, such as induction of hypervolemia in small animals and undesired effects of vasoactive drugs on central and peripheral baroreflex components. As an alternative, the sequence method, which consists in the computerized evaluation of naturally-occurring baroreflex adjustments of heart rate without the need for pharmacological administrations, was developed to study baroreflexes. In the present study, we compare this sequence method with the Oxford technique in two teleost species with different life styles, and we assess the optimal software configuration for the employment of the sequence method in fish. Calculation of baroreflex gain through the sequence method was adequate and reliable when the software was configured to search for baroreflex sequences with a minimum length of three cardiac cycles with a delay of one cardiac cycle between fluctuations in mean ventral aortic blood pressure and reflex changes in pulse interval. When properly configured, the sequence and the Oxford methods yielded similar determinations of the baroreflex gain in fish.