In Vitro Investigation of Insulin Dynamics During 4 Hours of Simulated Cardiopulmonary Bypass.

BACKGROUND: Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models. METHODS: Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type. RESULTS: Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01). CONCLUSIONS: Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.

Perioperative echocardiographic strain analysis: what anesthesiologists should know.

PURPOSE: Echocardiographic strain analysis by speckle tracking allows assessment of myocardial deformation during the cardiac cycle. Its clinical applications have significantly expanded over the last two decades as a sensitive marker of myocardial dysfunction with important diagnostic and prognostic values. Strain analysis has the potential to become a routine part of the perioperative echocardiographic examination for most anesthesiologist-echocardiographers but its exact role in the perioperative setting is still being defined. CLINICAL FEATURES: This clinical report reviews the principles underlying strain analysis and describes its main clinical uses pertinent to the field of anesthesiology and perioperative medicine. Strain for assessment of left and right ventricular function as well as atrial strain is described. We also discuss the potential role of strain to aid in perioperative risk stratification, surgical patient selection in cardiac surgery, and guidance of anesthetic monitor choice and clinical decision-making in the perioperative period. CONCLUSION: Echocardiographic strain analysis is a powerful tool that allows seeing what conventional 2D imaging sometimes fails to reveal. It often provides pathophysiologic insight into various cardiac diseases at an early stage. Strain analysis is readily feasible and reproducible thanks to the use of highly automated software platforms. This technique shows promising potential to become a valuable tool in the arsenal of the anesthesiologist-echocardiographer and aid in perioperative risk-stratification and clinical decision-making.

RéSUMé: OBJECTIF: L'analyse échocardiographique de la déformation cardiaque (strain analysis) par suivi des marqueurs acoustiques (speckle-tracking) permet d'évaluer la déformation du myocarde au cours du cycle cardiaque. Ses applications cliniques se sont considérablement développées au cours des deux dernières décennies en tant que marqueur sensible du dysfonctionnement myocardique, avec des valeurs diagnostiques et pronostiques importantes. L'analyse de la déformation cardiaque a le potentiel de devenir une partie intégrante de l'examen échocardiographique périopératoire de routine pour la plupart des anesthésiologistes-échocardiographes, mais son rôle exact dans le cadre périopératoire est encore en cours de définition. CARACTéRISTIQUES CLINIQUES: Ce rapport clinique passe en revue les principes qui sous-tendent l'analyse de la déformation cardiaque et décrit ses principales utilisations cliniques pertinentes dans le domaine de l'anesthésiologie et de la médecine périopératoire. L'analyse de la déformation cardique pour l'évaluation de la fonction ventriculaire gauche et droite ainsi que de la déformation auriculaire sont décrites. Nous discutons également du rôle potentiel de l'analyse de la déformation cardiaque pour aider à la stratification du risque périopératoire, à la sélection des patients en chirurgie cardiaque, à l'orientation du choix des moniteurs anesthésiques, et à la prise de décision clinique en période périopératoire. CONCLUSION: L'analyse échocardiographique de la déformation cardiaque est un outil puissant qui permet de voir ce que l'imagerie 2D conventionnelle ne parvient parfois pas à révéler. Elle fournit souvent un aperçu physiopathologique de diverses maladies cardiaques à un stade précoce. L'analyse de la déformation cardiaque est facilement réalisable et reproductible grâce à l'utilisation de plateformes logicielles hautement automatisées. Cette technique est potentiellement prometteuse et pourrait devenir un outil précieux dans l'arsenal de l'anesthésiologiste-échocardiographe et aider à la stratification du risque périopératoire et à la prise de décision clinique.

Perioperative hyperoxia- impact on myocardial biomarkers, strain and outcome in high-risk patients undergoing non-cardiac surgery: Protocol for a prospective randomized controlled trial.

BACKGROUND: Supplemental oxygen is used during every general anesthesia. However, for the maintenance phase of a general anesthesia, in most cases the longest part of anesthesia, only scarce evidence of dosing supplemental oxygen exists. Oxygen is a well-known coronary vasoconstrictor and thus may contribute to cardiovascular complications especially in vulnerable high-risk patients with coronary artery disease undergoing major non-cardiac surgery. Myocardial biomarkers are early indicators of myocardial injury. Oxygen supply demand mismatches due to coronary artery disease aggravated by hyperoxia might be displayed by changes from the biomarker's baseline-values. This study is designed to detect changes in myocardial biomarkers levels associated with perioperative hyperoxia. METHODS: This prospective randomized controlled interventional trial investigates the impact of maintaining perioperative high oxygen supplementation in high-risk patients undergoing non-cardiac vascular surgery on cardiac biomarkers, myocardial strain and outcome in 110 patients. Patients are allocated to be supplemented with either 0.3 (normal) or 0.8 (high) fraction of inspired oxygen (FiO2) perioperatively. Included is a short crossover phase during which transesophageal echocardiography is used to evaluate myocardial function at FiO2 0.3 and 0.8 by strain analysis in each patient. Patients will be followed up for complications at 30 days and 1 year. CONCLUSION: The trial is designed to evaluate perioperative changes from baseline myocardial biomarkers associated with perioperative FiO2. Furthermore, exploration and correlation of changes in biomarkers, acute early changes in myocardial function and clinical outcomes induced by different FiO2 may be possible.

Prognostic value of visual and quantitative CMR regional myocardial function in patients with suspected myocarditis.

According to updated Lake-Louise Criteria, impaired regional myocardial function serves as a supportive criterion in diagnosing myocarditis. This study aimed to assess visual regional wall motional abnormalities (RWMA) and novel quantitative regional longitudinal peak strain (RLS) for risk stratification in the clinical setting of myocarditis. In patients undergoing CMR and meeting clinical criteria for suspected myocarditis global longitudinal strain (GLS), late gadolinium enhancement (LGE), RWMA and RLS were assessed in the anterior, septal, inferior, and lateral regions and correlated to the occurrence of major adverse cardiac events (MACE), including heart failure hospitalization, sustained ventricular tachycardia, recurrent myocarditis, and all-cause death. In 690 consecutive patients (age: 48.0 ± 16.0 years; 37.7% female) with suspected myocarditis impaired RLS was correlated with RWMA and LV-GLS but not with the presence of LGE. At median follow up of 3.8 years, MACE occurred in 116 (16.8%) patients. Both, RWMA and RLS in anterior-, septal-, inferior-, and lateral- locations were univariately associated with outcomes (all p < 0.001), but not after adjusting for clinical characteristics and LV-GLS. In the subgroup of patients with normal LV function, RWMA were not predictive of outcomes, whereas septal RLS had incremental and independent prognostic value over clinical characteristics (HRadjusted = 1.132, 95% CI 1.020-1.256; p = 0.020). RWMA and RLS can be used to assess regional impairment of myocardial function in myocarditis but are of limited prognostic value in the overall population. However, in the subgroup of patients with normal LV function, septal RLS represents a distinctive marker of regional LV dysfunction, offering potential for risk-stratification.

Introducing a free-breathing MRI method to assess peri-operative myocardial oxygenation and function: A volunteer cohort study.

BACKGROUND: Induction of general anaesthesia has many potential triggers for peri-operative myocardial ischaemia including the acute disturbance of blood gases that frequently follows alterations in breathing and ventilation patterns. Free-breathing oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging may provide the opportunity to continuously quantify the impact of such triggers on myocardial oxygenation. OBJECTIVE: To investigate the impact of breathing patterns that simulate induction of general anaesthesia on myocardial oxygenation in awake healthy adults using continuous OS-CMR imaging. DESIGN: Prospective observational study. SETTING: Single-centre university hospital. Recruitment from August 2020 to January 2022. PARTICIPANTS: Thirty-two healthy volunteers younger than 45 years old were recruited. Data were analysed from n  = 29 (69% male individuals). INTERVENTION: Participants performed a simulated induction breathing manoeuvre consisting of 2.5 min paced breathing with a respiration rate of 14 breaths per minute, followed by 5 deep breaths, then apnoea for up to 60s inside a magnetic resonance imaging scanner (MRI). Cardiac images were acquired with the traditional OS-CMR sequence (OS bh-cine ), which requires apnoea for acquisition and with two free-breathing OS-CMR sequences: a high-resolution single-shot sequence (OS fb-ss ) and a real-time cine sequence (OS fb-rtcine ). MAIN OUTCOME MEASURES: Myocardial oxygenation response at the end of the paced breathing period and at the 30 s timepoint during the subsequent apnoea, reflecting the time of successful intubation in a clinical setting. RESULTS: The paced breathing followed by five deep breaths significantly reduced myocardial oxygenation, which was observed with all three techniques (OS bh-cine -6.0 ±â€Š2.6%, OS fb-ss -12.0 ±â€Š5.9%, OS fb-rtcine -5.4 ±â€Š7.0%, all P  < 0.05). The subsequent vasodilating stimulus of apnoea then significantly increased myocardial oxygenation (OS bh-cine 6.8 ±â€Š3.1%, OS fb-ss 8.4 ±â€Š5.6%, OS fb-rtcine 15.7 ±â€Š10.0%, all P  < 0.01). The free-breathing sequences were reproducible and were not inferior to the original sequence for any stage. CONCLUSION: Breathing manoeuvres simulating induction of general anaesthesia cause dynamic alterations of myocardial oxygenation in young volunteers, which can be quantified continuously with free-breathing OS-CMR. Introducing these new imaging techniques into peri-operative studies may throw new light into the mechanisms of peri-operative perturbations of myocardial tissue oxygenation and ischaemia. VISUAL ABSTRACT: http://links.lww.com/EJA/A922.

Focal and diffuse myocardial fibrosis both contribute to regional hypoperfusion assessed by post-processing quantitative-perfusion MRI techniques.

Introduction: Indications for stress-cardiovascular magnetic resonance imaging (CMR) to assess myocardial ischemia and viability are growing. First pass perfusion and late gadolinium enhancement (LGE) have limited value in balanced ischemia and diffuse fibrosis. Quantitative perfusion (QP) to assess absolute pixelwise myocardial blood flow (MBF) and extracellular volume (ECV) as a measure of diffuse fibrosis can overcome these limitations. We investigated the use of post-processing techniques for quantifying both pixelwise MBF and diffuse fibrosis in patients with clinically indicated CMR stress exams. We then assessed if focal and diffuse myocardial fibrosis and other features quantified during the CMR exam explain individual MBF findings. Methods: This prospective observational study enrolled 125 patients undergoing a clinically indicated stress-CMR scan. In addition to the clinical report, MBF during regadenoson-stress was quantified using a post-processing QP method and T1 maps were used to calculate ECV. Factors that were associated with poor MBF were investigated. Results: Of the 109 patients included (66 ± 11 years, 32% female), global and regional perfusion was quantified by QP analysis in both the presence and absence of visual first pass perfusion deficits. Similarly, ECV analysis identified diffuse fibrosis in myocardium beyond segments with LGE. Multivariable analysis showed both LGE (ß = -0.191, p = 0.001) and ECV (ß = -0.011, p < 0.001) were independent predictors of reduced MBF. In patients without clinically defined first pass perfusion deficits, the microvascular risk-factors of age and wall thickness further contributed to poor MBF (p < 0.001). Discussion: Quantitative analysis of MBF and diffuse fibrosis detected regional tissue abnormalities not identified by traditional visual assessment. Multi-parametric quantitative analysis may refine the work-up of the etiology of myocardial ischemia in patients referred for clinical CMR stress testing in the future and provide a deeper insight into ischemic heart disease.

Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis.

BACKGROUND: Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. METHODS: Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. RESULTS: Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> - 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04-1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12-1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02-1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. CONCLUSION: RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value.

Hyperoxia-induced deterioration of diastolic function in anaesthetised patients with coronary artery disease - Randomised crossover trial.

Background: There are no current recommendations for oxygen titration in patients with stable coronary artery disease. This study investigates the effect of iatrogenic hyperoxia on cardiac function in patients with coronary artery disease undergoing general anaesthesia. Methods: Patients scheduled for elective coronary artery bypass graft surgery were prospectively recruited into this randomised crossover clinical trial. All patients were exposed to inspired oxygen fractions of 0.3 (normoxaemia) and 0.8 (hyperoxia) in randomised order. A transoesophageal echocardiographic imaging protocol was performed during each exposure. Primary analysis investigated changes in 3D peak strain, whereas secondary analyses investigated other systolic and diastolic responses. Results: There was no statistical difference in systolic function between normoxaemia and hyperoxia. However, the response in systolic function to hyperoxia was dependent on ventricular function at normoxaemia. Patients with a normoxaemic left ventricular (LV) global longitudinal strain (GLS) poorer than the derived cut-off (>-15.4%) improved with hyperoxia (P<0.01), whereas in patients with normoxaemic LV-GLS <-15.4%, LV-GLS worsened with transition to hyperoxia (P<0.01). The same was seen for right ventricular GLS with a cut-off at -24.1%. Diastolic function worsened during hyperoxia indicated by a significant increase of averaged E/e' (8.6 [2.6]. vs 8.2 [2.4], P=0.01) and E/A ratio (1.4 (0.4) vs 1.3 (0.4), P=0.01). Conclusions: Although the response of biventricular systolic variables is dependent on systolic function at normoxaemia, diastolic function consistently worsens under hyperoxia. In coronary artery disease, intraoperative strain analysis may offer guidance for oxygen titration. Clinical trial registration: NCT04424433.

Analysis of bi-atrial function using CMR feature tracking and long-axis shortening approaches in patients with diastolic dysfunction and atrial fibrillation.

OBJECTIVES: Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. METHODS: Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. RESULTS: The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. CONCLUSION: Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. KEY POINTS: • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.

Performance of the Dexcom G6 Continuous Glucose Monitoring System During Cardiac Surgery Using Hypothermic Extracorporeal Circulation.

OBJECTIVE: Continuous glucose monitoring (CGM) may be challenged by extreme conditions during cardiac surgery using hypothermic extracorporeal circulation (ECC). RESEARCH DESIGN AND METHODS: We evaluated the Dexcom G6 sensor in 16 subjects undergoing cardiac surgery with hypothermic ECC, of whom 11 received deep hypothermic circulatory arrest (DHCA). Arterial blood glucose, quantified by the Accu-Chek Inform II meter, served as reference. RESULTS: Intrasurgery mean absolute relative difference (MARD) of 256 paired CGM/reference values was 23.8%. MARD was 29.1% during ECC (154 pairs) and 41.6% immediately after DHCA (10 pairs), with a negative bias (signed relative difference: -13.7%, -26.6%, and -41.6%). During surgery, 86.3% pairs were in Clarke error grid zones A or B and 41.0% of sensor readings fulfilled the International Organization for Standardization (ISO) 15197:2013 norm. Postsurgery, MARD was 15.0%. CONCLUSIONS: Cardiac surgery using hypothermic ECC challenges the accuracy of the Dexcom G6 CGM although recovery appears to occur thereafter.

Determination of selective antegrade perfusion flow rate in aortic arch surgery to restore baseline cerebral near-infrared spectroscopy values: a single-centre observational study.

OBJECTIVES: Neuroprotection during aortic arch surgery involves selective antegrade cerebral perfusion. The parameters of cerebral perfusion, e.g. flow rate, are inconsistent across centres and are subject of debate. The aim of this study was to determine the cerebral perfusion flow rate during hypothermic circulatory arrest required to meet preoperative awake baseline regional cerebral oxygen saturation (rSO2). METHODS: Patients scheduled for aortic arch surgery with hypothermic circulatory arrest were enrolled in this prospective observational study. After initiation of hypothermic circulatory arrest, bilateral selective antegrade cerebral perfusion was established and cerebral flow rate was continuously increased. The primary end point was the difference of cerebral saturation from baseline during cerebral perfusion flow rates of 6, 8 and 10 ml/kg/min. RESULTS: A total of 40 patients were included. During antegrade cerebral perfusion, rSO2 was significantly lower than the baseline at 6 ml/kg/min [-7.3, 95% confidence interval (CI): -1.7, -12.9; P = 0.0015]. In contrast, flow rates of 8 and 10 ml/kg/min resulted in rSO2 that did not significantly differ from the baseline (-2; 95% CI: -4.3, 8.3; P > 0.99 and 1.8; 95% CI: -8.5%, 4.8%; P > 0.99). Cerebral saturation was significantly more likely to meet baseline values during selective antegrade cerebral perfusion with 8 ml/kg/min than at 6 ml/kg/min (44.1%; 95% CI: 27.4%, 60.8% vs 11.8%; 95% CI: 0.9%, 22.6%; P = 0.0001). CONCLUSIONS: At 8 ml/kg/min cerebral flow rate during selective antegrade cerebral perfusion, regional cerebral oximetry baseline values are significantly more likely to be achieved than at 6 ml/kg/min. Further increasing the cerebral flow rate to 10 ml/kg/min does not significantly improve rSO2.

Feature tracking strain analysis detects the onset of regional diastolic dysfunction in territories with acute myocardial injury induced by transthoracic electrical interventions.

Electric interventions are used to terminate arrhythmia. However, myocardial injury from the electrical intervention can follow unique pathways and it is unknown how this affects regional ventricular function. This study investigated the impact of transthoracic electrical shocks on systolic and diastolic myocardial deformation. Ten healthy anaesthetized female swine received five transthoracic shocks (5 × 200 J) and six controls underwent a cardiovascular magnetic resonance exam prior to and 5 h after the intervention. Serial transthoracic shocks led to a global reduction in both left (LV, - 15.6 ± 3.3% to - 13.0 ± 3.6%, p < 0.01) and right ventricular (RV, - 16.1 ± 2.3% to - 12.8 ± 4.2%, p = 0.03) peak circumferential strain as a marker of systolic function and to a decrease in LV early diastolic strain rate (1.19 ± 0.35/s to 0.95 ± 0.37/s, p = 0.02), assessed by feature tracking analysis. The extent of myocardial edema (ΔT1) was related to an aggravation of regional LV and RV diastolic dysfunction, whereas only RV systolic function was regionally associated with an increase in T1. In conclusion, serial transthoracic shocks in a healthy swine model attenuate biventricular systolic function, but it is the acute development of regional diastolic dysfunction that is associated with the onset of colocalized myocardial edema.

Perioperative Doppler ultrasound assessment of portal vein flow pulsatility in high-risk cardiac surgery patients: a multicentre prospective cohort study.

BACKGROUND: Portal vein Doppler ultrasound pulsatility measured by transoesophageal echocardiography is a marker of the haemodynamic impact of venous congestion in cardiac surgery. We investigated whether the presence of abnormal portal vein flow pulsatility is associated with a longer duration of invasive life support and postoperative complications in high-risk patients. METHODS: In this multicentre cohort study, pulsed-wave Doppler ultrasound assessments of portal vein flow were performed during anaesthesia before initiation of cardiopulmonary bypass (before CPB) and after separation of cardiopulmonary bypass (after CPB). Abnormal pulsatility was defined as portal pulsatility fraction (PPF) ≥50% (PPF50). The primary outcome was the cumulative time in perioperative organ dysfunction (TPOD) requiring invasive life support during 28 days. Secondary outcomes included major postoperative complications. RESULTS: 373 patients, 71 (22.0%) had PPF50 before CPB and 77 (24.9%) after CPB. PPF50 was associated with longer duration of TPOD (median [inter-quartile range]; before CPB: 27 h [11-72] vs 19 h [8.5-42], P=0.02; after CPB: 27 h [11-61] vs 20 h [8-42], P=0.006). After adjusting for confounders, PPF50 before CPB showed significant association with TPOD. PPF50 after CPB was associated with a higher rate of major postoperative complications (36.4% vs 20.3%, P=0.006). CONCLUSIONS: Abnormal portal vein flow pulsatility before cardiopulmonary bypass was associated with longer duration of life support therapy after cardiac surgery in high-risk patients. Abnormal portal vein flow pulsatility after cardiopulmonary bypass separation was associated with a higher risk of major postoperative complications although this association was not independent of other factors. CLINICAL TRIAL REGISTRATION: NCT03656263.

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction.

Background: Microvascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE. Methods: Patients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort. Results: Forty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO-), and 314 (41%) segments showed no LGE (i.e., LGE-). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO-, and LGE-) showed an AUC = 0.764 and SCS cut-off value was -11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO- vs. LGE-) AUC = 0.848 and SCS with a cut-off value of -13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%. Conclusion: Segmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI.

Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial.

OBJECTIVE: Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. RESEARCH DESIGN AND METHODS: We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy according to local clinical practice (control group). Study treatment was administered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6-10.0 mmol/L). RESULTS: Forty-five patients were enrolled and assigned to the closed-loop (n = 23) or the control (n = 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P < 0.001). No episodes of severe hypoglycemia (<3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. CONCLUSIONS: In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia.

Combined Analysis of Myocardial Deformation and Oxygenation Detects Inducible Ischemia Unmasked by Breathing Maneuvers in Chronic Coronary Syndrome.

Introduction: In patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction. Methods: A group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain. Results: In healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p < 0.001) and augmented peak circumferential systolic strain (-3.3 ± 1.6%, p < 0.001). At the end of apnea, myocardial signal intensity had increased (+9.1 ± 5.3%, p < 0.001) and strain had normalized to baseline. CAD patients had a similar global oxygenation response to hyperventilation (-5.8 ± 9.6%, p = 0.085) but showed no change in peak strain from their resting state (-1.3 ± 1.6%), which was significantly attenuated in comparison the strain response observed in controls (p = 0.008). With apnea, the CAD patients showed an attenuated global oxygenation response to apnea compared to controls (+2.7 ± 6.2%, p < 0.001). This was accompanied by a significant depression of peak strain (3.0 ± 1.7%, p < 0.001), which also differed from the control response (p = 0.025). Regional analysis demonstrated that post-stenotic myocardium was most susceptible to de-oxygenation and systolic strain abnormalities during respiratory maneuvers. CMR measures at rest were unable to discriminate post-stenotic territory (p > 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone. Conclusion: In myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia.

Insights Into Myocardial Oxygenation and Cardiovascular Magnetic Resonance Tissue Biomarkers in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The pathophysiology of heart failure with preserved ejection fraction is not well understood, but evidence strongly suggests involvement of microvascular dysfunction. We studied the myocardial oxygenation reserve as a direct marker of coronary vascular function and its relation to myocardial deformation and tissue characteristics by cardiovascular magnetic resonance (CMR). METHODS: In a dual-center case-control study, patients with heart failure and preserved ejection fraction (>50%) and healthy controls older than 50 years underwent quantitative CMR for ventricular volumes and functional assessment with feature tracking, as well as tissue characterization (T1, T2, extracellular volume). Coronary vascular function was measured by oxygenation-sensitive (OS)-CMR of the myocardial oxygenation response to a vasoactive breathing maneuver. RESULTS: Twenty-nine patients completed the CMR exam. Compared with cutoffs derived from 12 control subjects, circumferential peak strain was attenuated in 97% of patients. Native T1 was elevated in 93%, extracellular volume was elevated in 83%. Sixty-six percent of patients revealed either regional or global myocardial edema, defined by an increased myocardial T2. An attenuated global myocardial oxygenation reserve (<4.4%) was observed in 96% of the patients (1.7±3.9% versus 9.1±5.3% in controls, P<0.001). This was correlated with septal wall thickness (r=-0.54, P=0.003), edema (myocardial T2; ß=-0.26% oxygenation-sensitive/ms [95% CI, -0.49 to -0.03], P=0.029), and reduced diastolic strain rate (ß=1.50% oxygenation-sensitive/s-1 [95% CI, 0.06-2.90], P=0.042). CONCLUSIONS: In patients with clinical heart failure with preserved ejection fraction, vascular dysfunction as measured by an attenuated myocardial oxygenation reserve is associated with myocardial edema, a thicker septum, and diastolic dysfunction. A quantitative comprehensive CMR exam including oxygenation-sensitive-CMR allows for comprehensive imaging-based phenotyping of heart failure with preserved ejection fraction.

Reproducibility and its confounders of CMR feature tracking myocardial strain analysis in patients with suspected myocarditis.

OBJECTIVES: Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique for assessing myocardial strain with valuable diagnostic and prognostic potential. However, the reproducibility of biventricular CMR-FT analysis in a large cardiovascular population has not been assessed. Also, evidence of confounders impacting reader reproducibility for CMR-FT in patients is unknown and currently limits the clinical implementation of this technique. METHODS: From a dual-center database of patients referred to CMR for suspected myocarditis, 125 patients were randomly selected to undergo biventricular CMR-FT analysis for 2-dimensional systolic and diastolic measures, with additional 3-dimensional analysis for the left ventricle. All image analysis was replicated by a single reader and by a second reader for intra- and inter-reader analysis (Circle Cardiovascular Imaging). Reliability was tested with intraclass correlation (ICC) tests, and the impact of imaging confounders on agreement was assessed through multivariable analysis. RESULTS: Left and right ventricular ejection fractions were reduced in 34% and 37% of the patients, respectively. Good to excellent reliability was shown for 2D (all ICC > 0.85) and 3D (all ICC > 0.70) peak strain and early diastolic strain rate for both ventricles in longitudinal orientation as well as circumferential orientations for the left ventricle. An increased slice number improved agreement while the presence of pericardial effusion compromised diastolic strain rate agreement, and arrhythmia compromised right ventricular agreement. CONCLUSION: In a large clinical cohort, we could show CMR-FT yields excellent inter-reader and intra-reader reproducibility. Multi-parametric CMR-FT of the right and left ventricles appears to be a robust tool in cardiovascular patients referred to CMR. CLINICALTRIALS: gov Identifier: NCT03470571, NCT04774549. Key Points • Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique to measure myocardial strain in cardiovascular patients referred for CMR; however, the evaluation of its reproducibility in a large cohort has not yet been performed. • In a large clinical cohort, CMR-FT yields excellent inter-reader and intra-reader reproducibility for both left and right ventricular systolic and diastolic parameters. • Arrhythmia and pericardial effusion compromise agreement of select FT parameters, but poor ejection fraction does not.