A novel speckle-tracking echocardiography parameter assessing left ventricular afterload.

BACKGROUND: Left ventricular stroke work index (LVSWI) and afterload-related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle-tracking echocardiography parameter, Pressure-Strain Product (PSP), can non-invasively predict catheter-based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub-phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis-like conditions. METHODS: Sixteen sheep with ARDS were randomly assigned to either (1) sepsis-like (n = 8) or (2) non-sepsis-like (n = 8) group. Each ARDS and sepsis-like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter-based LVSWI (the product of stroke work index, mean arterial pressure and .0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). RESULTS: PSPcirc showed a significant correlation with LVSWI (r2 = .66, p < .001) and ACP (r2 = .82, p < .001) in the sepsis-like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC .86) and ACP (AUC .88), and PSPrad predicted serum lactate (AUC .75) better than LV ejection fraction, global circumferential and radial strain. CONCLUSIONS: A novel PSP has the potential to non-invasively predict catheter-based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy.

Assessment and diagnosis of right ventricular failure-retrospection and future directions.

The right ventricle (RV) has a critical role in hemodynamics and right ventricular failure (RVF) often leads to poor clinical outcome. Despite the clinical importance of RVF, its definition and recognition currently rely on patients' symptoms and signs, rather than on objective parameters from quantifying RV dimensions and function. A key challenge is the geometrical complexity of the RV, which often makes it difficult to assess RV function accurately. There are several assessment modalities currently utilized in the clinical settings. Each diagnostic investigation has both advantages and limitations according to its characteristics. The purpose of this review is to reflect on the current diagnostic tools, consider the potential technological advancements and propose how to improve the assessment of right ventricular failure. Advanced technique such as automatic evaluation with artificial intelligence and 3-dimensional assessment for the complex RV structure has a potential to improve RV assessment by increasing accuracy and reproducibility of the measurements. Further, noninvasive assessments for RV-pulmonary artery coupling and right and left ventricular interaction are also warranted to overcome the load-related limitations for the accurate evaluation of RV contractile function. Future studies to cross-validate the advanced technologies in various populations are required.

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.

Left atrial strain imaging differentiates cardiac amyloidosis and hypertensive heart disease.

Echocardiographic diagnosis of cardiac amyloidosis (CA) can be difficult to differentiate from increased left ventricular (LV) wall thickness from hypertensive heart disease. The aim of this study was to evaluate left atrial (LA) function and deformation using strain and strain rate (SR) imaging in cardiac amyloidosis. We reviewed 44 cases of CA confirmed by tissue biopsy or a combination of clinical and cardiac imaging data. Cases were classified according two subgroups: amyloid light chain (AL) or amyloid transthyretin (ATTR). These subjects underwent 2D-Speckle tracking echocardiographic derived (STE) LA strain analysis. These were compared to 25 hypertensive (HT) patients with increased LV wall thickness. The three phases of LA function were evaluated using strain and strain rate parameters. Despite a similar increase in LV wall thickness, all LA strain parameters were significantly reduced in the AL cohort compared to the HT cohort (reservoir strain/LAs: 11.0 vs. 24.8%, p < 0.05). The ATTR cohort had significantly thicker LV walls and higher atrial fibrillation burden compared to AL and HT patients but similar reduction in LA strain values compared to AL group. A reservoir strain (S-LAs) cut off value of 20% was 86.4% sensitive and 88.6% specific for detecting CA compared to HT heart disease in this cohort. LA strain parameters were able to identify LA dysfunction in all types of CA. LA function in CA is significantly worse compared with hypertensive patients despite similar increase in LV wall thickness. In combination with other clinical and imaging features, LA strain may provide incremental value in differentiating cardiac amyloidosis from increased wall thickness secondary to hypertension.

Incremental Value of ePLAR-The Echocardiographic Pulmonary to Left Atrial Ratio in the Assessment of Sub-Massive Pulmonary Emboli.

BACKGROUND: Acute pulmonary embolism (PE) is characterized hemodynamically by abrupt obstruction in trans-pulmonary blood flow. The echocardiographic Pulmonary to Left Atrial ratio (ePLAR, tricuspid regurgitation Vmax/mitral E/e') has been validated as a non-invasive surrogate for trans-pulmonary gradient (TPG) that accurately differentiates pre-capillary from post-capillary chronic pulmonary hypertension. This study assessed ePLAR as an incremental echocardiographic assessment tool compared with traditional measures of right ventricular pressure and function. METHODS: In total, 110 (57.4 ± 17.6 years) patients with confirmed sub-massive pulmonary emboli with contemporaneous echocardiograms (0.3 ± 0.9 days) were compared with 110 age-matched controls (AMC). RESULTS: Tricuspid velocities were higher than AMC (2.6 ± 0.6 m/s vs. 2.4 ± 0.3 m/s, p < 0.05), although still consistent with "normal" right ventricular systolic pressures (34.2 ± 13.5 mmHg vs. 25 ± 5.3 mmHg, p < 0.05) with lower mitral E/e' values (8.2 ± 3.8 vs. 10.8 ± 5.1, p < 0.05). ePLAR values were higher than AMC (0.36 ± 0.14 m/s vs. 0.26 ± 0.10, p < 0.05) suggesting significantly elevated TPG. Detection of abnormal echocardiographic findings increased from 29% (TRVmax ≥ 2.9 m/s) and 32% (reduced tricuspid annular plane systolic excursion) to 70% with ePLAR ≥ 0.3 m/s. CONCLUSIONS: Raised ePLAR values in acute sub-massive pulmonary embolism suggest elevated trans-pulmonary gradients even in the absence of acutely increased pulmonary artery pressures. ePLAR dramatically increases the sensitivity of echocardiography for detection of hemodynamic perturbations in sub-massive pulmonary embolism patients, which may offer clinical utility in diagnosis and management.

Diastolic strain imaging: a new non-invasive tool to detect subclinical myocardial dysfunction in early cardiac allograft rejection.

Acute cellular rejection (ACR) remains a significant contributor to increased morbidity and mortality in heart transplant recipients. Early detection of ACR by non-invasive imaging is of potential clinical benefit. This study sought to investigate the use of non-invasive early global diastolic strain rate (GDSRe) and global longitudinal strain (GLS) in the detection of biopsy proven ACR. We retrospectively analysed 31 heart transplant patients (Mean age 52 ± 14 years) with biopsy proven ACR who underwent serial transthoracic echocardiographic examination and 2D strain analysis. Traditional echocardiographic systolic and diastolic parameters and novel systolic and diastolic strain imaging were measured during (1) early rejection free period (0R); (2) pre-rejection period (pre-1R); and (3) grade 1R acute cellular rejection (1R-ACR). GDSRe was significantly reduced (p = 0.0001) during the pre-rejection period (pre-1R) (0.74/s) when compared with 0R (0.97/s). GLS was only significantly reduced during 1R-ACR (17.7%), p = 0.001 but could not detect pre-1R (19.9%). Global diastolic strain rate at isovolumic relaxation showed no significant differences between any of the rejection periods. Traditional systolic and diastolic indices showed no significant differences. In conclusion, early global diastolic strain rate is the most sensitive parameter to detect subclinical myocardial dysfunction during early periods of pre-1R prior to biopsy confirmed 1R-ACR. GDSRe is a potential new tool for non-invasive screening of early post-transplant cardiac allograft rejection.

Echocardiographic assessment of myocardial function and mechanics during veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Transthoracic echocardiography (TTE) plays a fundamental role in the management of patients supported with extra-corporeal membrane oxygenation (ECMO). In light of fluctuating clinical states, serial monitoring of cardiac function is required. Formal quantification of ventricular parameters and myocardial mechanics offer benefit over qualitative assessment. The aim of this research was to compare unenhanced (UE) versus contrast-enhanced (CE) quantification of myocardial function and mechanics during ECMO in a validated ovine model. METHODS: Twenty-four sheep were commenced on peripheral veno-venous ECMO. Acute smoke-induced lung injury was induced in 21 sheep (3 controls). CE-TTE with Definity using Cadence Pulse Sequencing was performed. Two readers performed image analysis with TomTec Arena. End diastolic area (EDA, cm2), end systolic area (ESA, cm2), fractional area change (FAC, %), endocardial global circumferential strain (EGCS, %), myocardial global circumferential strain (MGCS, %), endocardial rotation (ER, degrees) and global radial strain (GRD, %) were evaluated for UE-TTE and CE-TTE. RESULTS: Full data sets are available in 22 sheep (92%). Mean CE EDA and ESA were significantly larger than in unenhanced images. Mean FAC was almost identical between the two techniques. There was no significant difference between UE and CE EGCS, MGCS and ER. There was significant difference in GRS between imaging techniques. Unenhanced inter-observer variability was from 0.48-0.70 but significantly improved to 0.71-0.89 for contrast imaging in all echocardiographic parameters. CONCLUSION: Semi-automated methods of myocardial function and mechanics using CE-TTE during ECMO was feasible and similar to UE-TTE for all parameters except ventricular areas and global radial strain. Addition of contrast significantly decreased inter-observer variability of all measurements.

The effects of normovolemic anemia and blood transfusion on cerebral microcirculation after severe head injury.

BACKGROUND: Cerebral regional microcirculation is altered following severe head injury. In addition to tissue disruption, partial pressure of tissue oxygenation is impaired due to an increase in the oxygen tissue gradient. The heterogenic distribution of cerebral microcirculation is multifactorial, and acute anemia challenges further the delivery of oxygen to tissues. Currently, a restrictive transfusion threshold is globally applied; however, it is unclear how anemia modifies regional cerebral microcirculation; hence, it is unclear if by aiming to a global endpoint, specific anatomical regions undergo ischemia. This study aims to quantify the temporal changes in cerebral microcirculation after severe head injury, under the effect of anemia and transfusion. It also aims to assess its effects specifically at the ischemic penumbra compared to contralateral regions and its interactions with axonal integrity in real time. Twelve ovine models were subjected to a severe contusion and acceleration-deceleration injury. Normovolemic anemia to a restrictive threshold was maintained after injury, followed by autologous transfusion. Direct quantification of cerebral microcirculation used cytometric count of color-coded microspheres. Axonal injury was assessed using amyloid precursor protein staining. RESULTS: A mixed-effect regression model from pre-transfusion to post-transfusion times with a random intercept for each sheep was used. Cerebral microcirculation amongst subjects with normal intracranial pressure was maintained from baseline and increased further after transfusion. Subjects with high intracranial pressure had a consistent reduction of their microcirculation to ischemic thresholds (20-30 ml/100 g/min) without an improvement after transfusion. Cerebral PtiO2 was reduced when exposed to anemia but increased in a 9.6-fold with transfusion 95% CI 5.6 to 13.6 (p value < 0.001). CONCLUSIONS: After severe head injury, the exposure to normovolemic anemia to a restrictive transfusion threshold, leads to a consistent reduction on cerebral microcirculation below ischemic thresholds, independent of cerebral perfusion pressure. Amongst subjects with raised intracranial pressure, microcirculation does not improve after transfusion. Cerebral oxymetry is impaired during anemia with a statistically significant increase after transfusion. Current transfusion practices in neurocritical care are based on a rigid hemoglobin threshold, a view that excludes cerebral metabolic demands and specific needs. An RCT exploring these concepts is warranted.

Cerebral Microcirculation and Histological Mapping After Severe Head Injury: A Contusion and Acceleration Experimental Model.

BACKGROUND: Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow. OBJECTIVE: This study assesses the changes of cerebral microcirculation blood flow over time after an experimental brain injury model in sheep and contrasts these findings with the histological analysis of the same regions with the aim of mapping cerebral flow and tissue changes after injury. METHODS: Microcirculation was quantified using flow cytometry of color microspheres injected under intracardiac ultrasound to ensure systemic and homogeneous distribution. Histological analysis used amyloid precursor protein staining as a marker of axonal injury. A mapping of microcirculation and axonal staining was performed using adjacent layers of tissue from the same anatomical area, allowing flow and tissue data to be available from the same anatomical region. A mixed effect regression model assessed microcirculation during 4 h after injury, and those results were then contrasted to the amyloid staining qualitative score. RESULTS: Microcirculation values for each subject and tissue region over time, including baseline, ranged between 20 and 80 ml/100 g/min with means that did not differ statistically from baseline flows. However, microcirculation values for each subject and tissue region were reduced from baseline, although their confidence intervals crossing the horizontal ratio of 1 indicated that such reduction was not statistically significant. Histological analysis demonstrated the presence of moderate and severe score on the amyloid staining throughout both hemispheres. CONCLUSION: Microcirculation at the ipsilateral and contralateral site of a contusion and the ipsilateral thalamus and medulla showed a consistent decline over time. Our data suggest that after severe head injury, microcirculation in predefined areas of the brain is reduced from baseline with amyloid staining in those areas reflecting the early establishment of axonal injury.

Topographical distribution of perioperative cerebral infarction associated with transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is associated with a high incidence of cerebrovascular injury. As these injuries are thought to be primarily embolic, neuroprotection strategies have focused on embolic protection devices. However, the topographical distribution of cerebral emboli and how this impacts on the effectiveness of these devices have not been thoroughly assessed. Here, we evaluated the anatomical characteristics of magnetic resonance imaging (MRI)-defined cerebral ischemic lesions occurring secondary to TAVI to enhance our understanding of the distribution of cardioembolic phenomena. METHODS: Forty patients undergoing transfemoral TAVI with an Edwards SAPIEN-XT valve under general anesthesia were enrolled prospectively in this observational study. Participants underwent brain MRI preprocedure, and 3 ± 1 days and 6 ± 1 months postprocedure. RESULTS: Mean ± SD participant age was 82 ± 7 years. Patients had an intermediate to high surgical risk, with a mean Society of Thoracic Surgeons score of 6.3 ± 3.5 and EuroSCORE of 18.1 ± 10.6. Post-TAVI, there were no clinically apparent cerebrovascular events, but MRI assessments identified 83 new lesions across 19 of 31 (61%) participants, with a median ± interquartile range number and volume of 1 ± 2.8 lesions and 20 ± 190 µL per patient. By volume, 80% of the infarcts were cortical, 90% in the posterior circulation and 81% in the right hemisphere. CONCLUSIONS: The distribution of lesions that we detected suggests that cortical gray matter, the posterior circulation, and the right hemisphere are all particularly vulnerable to perioperative cerebrovascular injury. This finding has implications for the use of intraoperative cerebral embolic protection devices, particularly those that leave the left subclavian and, therefore, left vertebral artery unprotected.

Reliability of thermodilution derived cardiac output with different operator characteristics.

Cardiac output (CO) is commonly measured using the thermodilution technique at the time of right heart catheterisation (RHC). However inter-operator variability, and the operator characteristics which may influence that, has not been quantified. Therefore, this study aimed to assess inter-operator variability with the thermodilution technique using a mock circulation loop (MCL) with calibrated flow sensors. Participants were blinded and asked to determine 4 levels of CO using the thermodilution technique, which was compared with the MCL calibrated flow sensors. The MCL was used to randomly generate CO between 3.0 and 7.0 L/min through changes in heart rate, contractility and vascular resistance with a RHC inserted through the MCL pulmonary artery. Participant characteristics including gender, specialty, age, height, weight, body-mass index, grip strength and RHC experience were recorded and compared to determine their relationship with CO measurement accuracy. In total, there were 15 participants, made up of consultant cardiologists (6), advanced trainees in cardiology (5) and intensive care consultants (4). The majority (9) had performed 26-100 previous RHCs, while 4 had performed more than 100 RHCs. Compared to the MCL-measured CO, participants overestimated CO using the thermodilution technique with a mean difference of +0.75 ± 0.71 L/min. The overall r2 value for actual vs measured CO was 0.85. The difference between MCL and thermodilution derived CO declined significantly with increasing RHC experience (P < 0.001), increasing body mass index (P < 0.001) and decreasing grip strength (P = 0.033). This study demonstrated that the thermodilution technique is a reasonable method to determine CO, and that operator experience was the only participant characteristic related to CO measurement accuracy. Our results suggest that adequate exposure to, and training in, the thermodilution technique is required for clinicians who perform RHC.

Contrast Microsphere Destruction by a Continuous Flow Ventricular Assist Device: An In Vitro Evaluation Using a Mock Circulation Loop.

OBJECTIVES: Transthoracic echocardiography (TTE) is fundamental in managing patients supported with ventricular assist devices (VAD). However imaging can be difficult in these patients. Contrast improves image quality but they are hydrodynamically fragile agents. The aim was to assess contrast concentration following passage through a VAD utilising a mock circulation loop (MCL). METHODS: Heartware continuous flow (CF) VAD was incorporated into a MCL. Definity® contrast was infused into the MCL with imaging before and after CF-VAD. 5 mm2 regions of interest were used to obtain signal intensity (decibels), as a surrogate of contrast concentration. RESULTS: Four pump speeds revealed significant reduction in contrast signal intensity after CF-VAD compared to before CF-VAD (all p < 0.0001). Combined pre- and postpump data at all speeds showed a 22.2% absolute reduction in contrast signal intensity across the CF-VAD (14.8 ± 0.8 dB prepump versus 11.6 ± 1.4 dB postpump; p < 0.0001). Mean signal intensity reduction at each speed showed an inverse relationship between speed and relative reduction in signal intensity. CONCLUSION: Contrast microsphere transit through a CF-VAD within a MCL resulted in significant reduction in signal intensity, consistent with destruction within the pump. This was evident at all CF-VAD pump speeds but relative signal drop was inversely proportional to pump speed.

Contrast microsphere enhancement of the tricuspid regurgitant spectral Doppler signal - Is it still necessary with contemporary scanners?

BACKGROUND: Accurate evaluation of the tricuspid regurgitant (TR) spectral Doppler signal is important during transthoracic echocardiographic (TTE) evaluation for pulmonary hypertension (PHT). Contrast enhancement improves Doppler backscatter. However, its incremental benefit with contemporary scanners is less well established. The aim of this study was to assess whether the TR spectral Doppler signal using contemporary scanners was improved using a second generation contrast agent, Definity® (CE), compared to unenhanced TTE (UE). METHODS: Analysis of patients who underwent UE then CE TR interrogation was performed. TR signal was evaluated by an experienced reader and graded 1 (clear-high level of confidence of interpretation and complete spectral Doppler envelope), 2 (suboptimal with medium-low level of confidence of interpretation and incomplete envelope), 3 (poor-absent and no measurable spectral Doppler signal). Maximal TR velocity (TRV) was defined as peak velocity that could be clearly identified. An inexperienced sonographer read 30 randomly selected studies. RESULTS: 176 TTE were performed in 173 patients (mean age 57 ± 14.8 years). Wilcoxon signed rank test demonstrated significant improvement (p < 0.0001) in TR spectral Doppler signal quality with CE TTE. Mean score CE TTE vs. TTE = 2.32 ± 0.85 vs. 2.56 ± 0.75 respectively (p < 0.0001). Mean maximal TRV CE TTE vs. UE TTE = 2.61 ± 0.44 m/s vs. 2.54 ± 0.49 m/s respectively (p < 0.0001). The inexperienced reader had a greater improvement in scoring CE TTE signals vs. UE TTE (p < 0.0001). CONCLUSION: In the era of contemporary scanners, CE improved the ability to detect and measure TRV, except in those with clear unenhanced TR spectral Doppler signals or greater than mild tricuspid regurgitation.

Intervendor consistency and reproducibility of left ventricular 2D global and regional strain with two different high-end ultrasound systems.

AIMS: We aimed to assess intervendor agreement of global (GLS) and regional longitudinal strain by vendor-specific software after EACVI/ASE Industry Task Force Standardization Initiatives for Deformation Imaging. METHODS AND RESULTS: Fifty-five patients underwent prospective dataset acquisitions on the same day by the same operator using two commercially available cardiac ultrasound systems (GE Vivid E9 and Philips iE33). GLS and regional peak longitudinal strain were analyzed offline using corresponding vendor-specific software (EchoPAC BT13 and QLAB version 10.3). Absolute mean GLS measurements were similar between the two vendors (GE -17.5 ± 5.2% vs. Philips -18.9 ± 5.1%, P = 0.15). There was excellent intervendor correlation of GLS by the same observer [r = 0.94, P < 0.0001; bias -1.3%, 95% CI limits of agreement (LOA) -4.8 to 2.2%). Intervendor comparison for regional longitudinal strain by coronary artery territories distribution were: LAD: r = 0.85, P < 0.0001; bias 0.5%, LOA -5.3 to 6.4%; RCA: r = 0.88, P < 0.0001; bias -2.4%, LOA -8.6 to 3.7%; LCX: r = 0.76, P < 0.0001; bias -5.3%, LOA -10.6 to 2.0%. Intervendor comparison for regional longitudinal strain by LV levels were: basal: r = 0.86, P < 0.0001; bias -3.6%, LOA -9.9 to 2.0%; mid: r = 0.90, P < 0.0001; bias -2.6%, LOA -7.8 to 2.6%; apical: r = 0.74; P < 0.0001; bias -1.3%, LOA -9.4 to 6.8%. CONCLUSIONS: Intervendor agreement in GLS and regional strain measurements have significantly improved after the EACVI/ASE Task Force Strain Standardization Initiatives. However, significant wide LOA still exist, especially for regional strain measurements, which remains relevant when considering vendor-specific software for serial measurements.

Neurological Injury in Intermediate-Risk Transcatheter Aortic Valve Implantation.

BACKGROUND: The application of transcatheter aortic valve implantation (TAVI) to intermediate-risk patients is a controversial issue. Of concern, neurological injury in this group remains poorly defined. Among high-risk and inoperable patients, subclinical injury is reported on average in 75% undergoing the procedure. Although this attendant risk may be acceptable in higher-risk patients, it may not be so in those of lower risk. METHODS AND RESULTS: Forty patients undergoing TAVI with the Edwards SAPIEN-XT™ prosthesis were prospectively studied. Patients were of intermediate surgical risk, with a mean±standard deviation Society of Thoracic Surgeons score of 5.1±2.5% and a EuroSCORE II of 4.8±2.4%; participant age was 82±7 years. Clinically apparent injury was assessed by serial National Institutes of Health Stroke Scale assessments, Montreal Cognitive Assessments (MoCA), and with the Confusion Assessment Method. These identified 1 (2.5%) minor stroke, 1 (2.5%) episode of postoperative delirium, and 2 patients (5%) with significant postoperative cognitive dysfunction. Subclinical neurological injury was assessed using brain magnetic resonance imaging, including diffusion-weighted imaging (DWI) sequences preprocedure and at 3±1 days postprocedure. This identified 68 new DWI lesions present in 60% of participants, with a median±interquartile range of 1±3 lesions/patient and volumes of infarction of 24±19 µL/lesion and 89±218 µL/patient. DWI lesions were associated with a statistically significant reduction in early cognition (mean ΔMoCA -3.5±1.7) without effect on cognition, quality of life, or functional capacity at 6 months. CONCLUSIONS: Objectively measured subclinical neurological injuries remain a concern in intermediate-risk patients undergoing TAVI and are likely to manifest with early neurocognitive changes. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Australian & New Zealand Clinical Trials Registry: ACTRN12613000083796.

Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review.

BACKGROUND: Recent research has identified an increased rate of mortality associated with fluid bolus therapy for severe sepsis and septic shock, but the mechanisms are still not well understood. Fluid resuscitation therapy administered for sepsis and septic shock targets restoration of the macro-circulation, but the pathogenesis of sepsis is complex and includes microcirculatory dysfunction. OBJECTIVE: The objective of the study is to systematically review data comparing the effects of different types of fluid resuscitation on the microcirculation in clinically relevant animal models of lipopolysaccharide-induced sepsis. METHODS: A structured search of PubMed/MEDLINE and EMBASE for relevant publications from 1 January 1990 to 31 December 2015 was performed, in accordance with PRISMA guidelines. RESULTS: The number of published papers on sepsis and the microcirculation has increased steadily over the last 25 years. We identified 11 experimental animal studies comparing the effects of different fluid resuscitation regimens on the microcirculation. Heterogeneity precluded any meta-analysis. CONCLUSIONS: Few animal model studies have been published comparing the microcirculatory effects of different types of fluid resuscitation for sepsis and septic shock. Biologically relevant animal model studies remain necessary to enhance understanding regarding the mechanisms by which fluid resuscitation affects the microcirculation and to facilitate the transfer of basic science discoveries to clinical applications.

Cerebral microcirculation during mild head injury after a contusion and acceleration experimental model in sheep.

BACKGROUND: Cerebral microcirculation after head injury is heterogeneous and temporally variable. Regions at risk of infarction such as peri-contusional areas are vulnerable to anaemia. However, direct quantification of the cerebral microcirculation is clinically not feasible. This study describes a novel experimental head injury model correlating cerebral microcirculation with histopathology analysis. OBJECTIVE: To test the hypothesis that cerebral microcirculation at the ischaemic penumbrae is reduced over time when compared with non-injured regions. METHODS: Merino sheep were instrumented using a transeptal catheter to inject coded microspheres into the left cardiac atrium, ensuring systemic distribution. After a blunt impact over the left parietal region, cytometric analyses quantified cerebral microcirculation and amyloid precursor protein staining identified axonal injury in pre-defined anatomical regions. A mixed effect regression model assessed the hourly blood flow results during 4 hours after injury. RESULTS: Cerebral microcirculation showed temporal reductions with minimal amyloid staining except for the ipsilateral thalamus and medulla. CONCLUSION: The spatial heterogeneity and temporal reduction of cerebral microcirculation in ovine models occur early, even after mild head injury, independent of the intracranial pressure and the level of haemoglobin. Alternate approaches to ensure recovery of regions with reversible injury require a targeted assessment of cerebral microcirculation.

ePLAR - The echocardiographic Pulmonary to Left Atrial Ratio - A novel non-invasive parameter to differentiate pre-capillary and post-capillary pulmonary hypertension.

BACKGROUND: Right heart catheterisation is the gold-standard for differentiating pre-capillary pulmonary hypertension (high mean pulmonary artery pressure, normal pulmonary wedge pressure) from post-capillary physiology (elevated pulmonary wedge pressure). The new non-invasive parameter, ePLAR (echocardiographic Pulmonary to Left Atrial Ratio) is calculated from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave:septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). METHODS: Pulmonary hypertension patients (mean pulmonary artery pressure>25mmHg, n=133, 66 male, average 65.0±16.8years) were classified by right heart catheterisation as pre-capillary or post-capillary [subdivided into isolated post-capillary (diastolic pulmonary gradient <7mmHg) or combined pre- and post-capillary cases]. The ePLAR values of these groups were compared to each other and to a population sample of 16,356 population reference echocardiograms. RESULTS: ePLAR values for the normal reference population of 16,356 echocardiograms (age 56±16.6years) were 0.30±0.09m/s. Pre-capillary pulmonary hypertension patients (n=35, 26 male, PAPsys 63.9±16.6mmHg, PAPdiast 24.1±7.3mmHg, PAPmean 37.9±9.4mmHg, PCWP 10.6±2.7mmHg) had significantly higher ePLAR values than post-capillary cases (n=98, 40 male, PAPsys 59.9±17.6mmHg, PAPdiast 25.0±7.4mmHg, PAPmean 38.1±9.8mmHg, PCWP 23.5±6.4mmHg)-ePLAR 0.44±0.22m/s vs 0.20±0.11m/s (p<0.001). ePLAR values were significantly lower in isolated post-capillary pulmonary hypertension than in combined pre- and post-capillary cases (0.18±0.08m/s vs 0.28±0.18m/s, p<0.001). CONCLUSIONS: ePLAR is a simple echocardiographic parameter which can accurately differentiate the smaller subset of patients with pre-capillary pulmonary hypertension from the more common post-capillary aetiology. The use of this easily obtained echocardiographic parameter has the potential to enhance non-invasive triage of patients for specific pulmonary vasodilator therapy.