Cost-effectiveness of ECPR versus CCPR in OHCA; A pre-planned, trial-based economic evaluation.

INTRODUCTION: When out-of-hospital cardiac arrest (OHCA) becomes refractory, extracorporeal cardiopulmonary resuscitation (ECPR) is a potential option to restore circulation and improve the patient's outcome. However, ECPR requires specific materials and highly skilled personnel, and it is unclear whether increased survival and health-related quality of life (HRQOL) justify these costs. METHODS: This cost-effectiveness study was part of the INCEPTION study, a multicenter, pragmatic randomized trial comparing hospital-based ECPR to conventional CPR (CCPR) in patients with refractory OHCA in 10 cardiosurgical centers in the Netherlands. We analyzed healthcare costs in the first year and measured HRQOL using the EQ-5D-5L at 1, 3, 6, and 12 months. Incremental cost-effectiveness ratio's (ICER), cost-effectiveness planes, and acceptability curves were calculated. Sensitivity analyses were performed for per-protocol and as-treated subgroups as well as imputed productivity loss in deceased patients. RESULTS: In total 132 patients were enrolled: 62 in the CCPR and 70 in the ECPR group. The difference in mean costs after one year was €5,109 (95%CI -7,264-15,764). Mean QALY after one year was 0.15 in the ECPR group and 0.11 in the CCPR group, resulting in an ICER of €121,643 per additional QALY gained. The acceptability curve shows that at a willingness-to-pay threshold of €80.000, the probability of ECPR being cost-effective compared to CCPR is 36%. Sensitivity analysis showed increasing ICER in the per-protocol and as-treated groups and lower probabilities of acceptance. CONCLUSION: Hospital-based ECPR in refractory OHCA has a low probability of being cost-effective in a trial-based economic evaluation.

A national multi centre pre-hospital ECPR stepped wedge study; design and rationale of the ON-SCENE study.

BACKGROUND: The likelihood of return of spontaneous circulation with conventional advanced life support is known to have an exponential decline and therefore neurological outcome after 20 min in patients with a cardiac arrest is poor. Initiation of venoarterial ExtraCorporeal Membrane Oxygenation (ECMO) during resuscitation might improve outcomes if used in time and in a selected patient category. However, previous studies have failed to significantly reduce the time from cardiac arrest to ECMO flow to less than 60 min. We hypothesize that the initiation of Extracorporeal Cardiopulmonary Resuscitation (ECPR) by a Helicopter Emergency Medical Services System (HEMS) will reduce the low flow time and improve outcomes in refractory Out of Hospital Cardiac Arrest (OHCA) patients. METHODS: The ON-SCENE study will use a non-randomised stepped wedge design to implement ECPR in patients with witnessed OHCA between the ages of 18-50 years old, with an initial presentation of shockable rhythm or pulseless electrical activity with a high suspicion of pulmonary embolism, lasting more than 20, but less than 45 min. Patients will be treated by the ambulance crew and HEMS with prehospital ECPR capabilities and will be compared with treatment by ambulance crew and HEMS without prehospital ECPR capabilities. The primary outcome measure will be survival at hospital discharge. The secondary outcome measure will be good neurological outcome defined as a cerebral performance categories scale score of 1 or 2 at 6 and 12 months. DISCUSSION: The ON-SCENE study focuses on initiating ECPR at the scene of OHCA using HEMS. The current in-hospital ECPR for OHCA obstacles encompassing low survival rates in refractory arrests, extended low-flow durations during transportation, and the critical time sensitivity of initiating ECPR, which could potentially be addressed through the implementation of the HEMS system. When successful, implementing on-scene ECPR could significantly enhance survival rates and minimize neurological impairment. TRIAL REGISTRATION: Clinicaltyrials.gov under NCT04620070, registration date 3 November 2020.

Proning the extracorporeal membrane oxygenation plus Impella: a case report.

Background: The prone position is recommended as supportive therapy in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). However, little is known about prone position ventilation in patients with cardiogenic shock supported by extracorporeal membrane oxygenation (ECMO) plus Impella (ECPELLA) developing ARDS. Case summary: A 66-year-old man with severe left ventricular dysfunction was admitted to a non-academic ECMO centre for a high-risk coronary artery bypass grafting. He developed post-cardiotomy shock needing ECMO support. To improve left ventricular unloading, an Impella was inserted 2 days later. One day later, he developed ARDS and needed prone position ventilation with ECPELLA in situ. After 4 weeks, he was discharged from the intensive care unit. Discussion: Previous studies demonstrated that prone positioning could help avoid an additional venous cannula in veno-arterial ECMO patients, which is associated with mechanical complications. In this case, there was a promising role for unloading the left ventricle with Impella during veno-arterial ECMO and, for proning, the patient with cardiogenic shock developing ARDS during ECMO support without the need for an extra venous cannula.

Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive. METHODS: In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis. RESULTS: Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups. CONCLUSIONS: In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).

Characteristics and Outcome of Patients With a History of Cancer Undergoing Durable Left Ventricular Assist Device Implantation.

BACKGROUND: Patients with cancer (patients with a history of cancer) with advanced heart failure are increasing, but unlikely to be transplanted, and left ventricular assist device (LVAD) is an alternative strategy. This study investigates the characteristics and outcomes of patients with cancer undergoing durable LVAD. METHODS: Adult patients with a history of cancer who received LVADs were identified from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry: 2008 and 2017. Characteristics and outcomes between patients with cancer and those without cancer were compared, and subgroup analyses of cancer therapy-induced cardiomyopathy (CCM) and non-CCM were also conducted. RESULTS: Overall, 1273 (6.5%) patients had a history of cancer, including 289 (22.7%) with CCM and 984 (77.3%) with non-CCM as the primary reason for heart failure. Patients with cancer had shorter median survival (3.72 versus 3.97 years, log-rank P=0.002), and multivariable Cox and competing risk regressions revealed that a history of cancer was associated with reduced survival (hazard ratio, 1.14 [95% CI, 1.04-1.26]; P=0.005; subdistribution hazard ratio, 1.24 [95% CI, 1.13-1.36]; P<0.001) and decreased incidence of heart transplantation. There was no significant difference in mortality between patients with CCM-induced heart failure and patients without cancer. Patients with cancer experienced an increased risk of bleeding, and age, INTERMACS profile, albumin, dialysis, and blood urea nitrogen were associated with mortality in these patients. CONCLUSIONS: A history of cancer is associated with mildly reduced survival, lower incidence of heart transplantation, and increased risk of bleeding after LVAD, whereas the survival in patients with cancer with CCM-induced heart failure is similar to those without cancer. LVAD implantation in patients with cancer is very well possible.

Sublingual microcirculation: comparison between the 415 nm blue light and 520 nm green light of sidestream dark field videomicroscopes.

Green light with a wavelength of 520 nm is commonly used in sidestream dark field (SDF) video microscopes for sublingual microcirculation assessment in clinical practice. However, blue light could obtain a clearer microcirculatory image due to a higher light absorption coefficient of hemoglobin. The aim of this study was to compare the sublingual microcirculatory image quality acquisition and related microcirculatory parameters between 520 nm green light and 415 nm blue light probes in the SDF device named MicroSee V100. Sublingual microcirculation films from twenty-one healthy volunteers were prospectively collected by blue light and green light probes, and only one video of each wavelength was recorded and analyzed in each volunteer. Moreover, 200 sublingual microcirculation films (100 by blue light probe and 100 by green light probe) of ICU patients were retrospectively scored for microcirculation image quality. Compared to green light, an increase in the perfused vessel density (paired t test, increased by 4.6 ± 4.7 mm/mm2, P < 0.0001) and total vessel density (paired t test, increased by 5.1 ± 4.6 mm/mm2, P < 0.0001) was observed by blue light in the healthy volunteers. The blue light probe had a significantly lower rate of unacceptable films than the green light probe in the 200 films of ICU patients (10/100 vs. 39/100, P < 0.0001). Blue light provides a higher microcirculatory vessel density and image quality than the existing SDF probe using green light.

Microcirculatory alterations in critically ill COVID-19 patients analyzed using artificial intelligence.

BACKGROUND: The sublingual microcirculation presumably exhibits disease-specific changes in function and morphology. Algorithm-based quantification of functional microcirculatory hemodynamic variables in handheld vital microscopy (HVM) has recently allowed identification of hemodynamic alterations in the microcirculation associated with COVID-19. In the present study we hypothesized that supervised deep machine learning could be used to identify previously unknown microcirculatory alterations, and combination with algorithmically quantified functional variables increases the model's performance to differentiate critically ill COVID-19 patients from healthy volunteers. METHODS: Four international, multi-central cohorts of critically ill COVID-19 patients and healthy volunteers (n = 59/n = 40) were used for neuronal network training and internal validation, alongside quantification of functional microcirculatory hemodynamic variables. Independent verification of the models was performed in a second cohort (n = 25/n = 33). RESULTS: Six thousand ninety-two image sequences in 157 individuals were included. Bootstrapped internal validation yielded AUROC(CI) for detection of COVID-19 status of 0.75 (0.69-0.79), 0.74 (0.69-0.79) and 0.84 (0.80-0.89) for the algorithm-based, deep learning-based and combined models. Individual model performance in external validation was 0.73 (0.71-0.76) and 0.61 (0.58-0.63). Combined neuronal network and algorithm-based identification yielded the highest externally validated AUROC of 0.75 (0.73-0.78) (P < 0.0001 versus internal validation and individual models). CONCLUSIONS: We successfully trained a deep learning-based model to differentiate critically ill COVID-19 patients from heathy volunteers in sublingual HVM image sequences. Internally validated, deep learning was superior to the algorithmic approach. However, combining the deep learning method with an algorithm-based approach to quantify the functional state of the microcirculation markedly increased the sensitivity and specificity as compared to either approach alone, and enabled successful external validation of the identification of the presence of microcirculatory alterations associated with COVID-19 status.

Venous-arterial CO2 to arterial-venous O2 content ratio in different shock types and correlation with hypoxia indicators.

Introduction: Shock is a generalized form of acute circulatory failure characterized by low tissue perfusion. If not recognized early, it highly increases patient morbidity and mortality. Central venous-arterial CO2 (Carbon dioxide) to arterial-central venous O2 (Oxygen) content ratio (Pcv-aCO2/Ca-cvO2) has been used for the early prediction of anaerobic metabolism in septic shock patients. However, knowledge about the usability of this ratio in cardiogenic shock is scarce. Materials and Methods: We retrospectively collected the data of patients admitted to our 18-bed intensive care unit (Haga Hospital, Department of Intensive Care, The Hague, The Netherlands) with a diagnosis of septic shock or cardiogenic shock in 2018. All patients who had undergone Swan-Ganz or Pulse index Continuous Cardiac Output device insertion were included in the study. The hemodynamic variables were recorded both at ICU admission and during catheterization. Result: Forty-six (n= 46) patients with a mean age of 62 ± 13 years and 52% female gender were enrolled in the study. The Acute Physiology and Chronic Health Evaluation IV (APACHE IV) score was 96 ± 39. Twenty-four patients had septic shock, and twenty-two were diagnosed with cardiogenic shock. Although Pcv-aCO2 (Central venous-arterial CO2) and ScvO2 (Central venous oxygen) were not found different between the cardiogenic and septic shock groups, the Pcv-aCO2/Ca-cvO2 ratio was significantly lower in patients with cardiogenic shock (p= 0.035). The Pcv-aCO2/Ca-cvO2 ratio had a weak correlation with ScvO2 (r= 0.21, p= 0.040). Pcv-aCO2 and ScvO2 showed negative lower moderate correlation (r= -0.40, p= 0.030). Twenty patients [nine (19%) with cardiogenic shock, and eleven (23%) with septic shock] died during their ICU or hospital stay. Although Ca-cvO2, Pcv-aCO2, and ScvO2 were not associated with mortality, a higher Pcv-aCO2/Ca-cvO2 ratio was associated with increased mortality (p= 0.035). Conclusions: The Pcv-aCO2/Ca-cvO2 ratio is a valuable hypoxia indicator in states of shock. However, cutoff levels should be identified for different shock types.

Case Report: Early Identification of Subclinical Cardiac Tamponade in a Patient With a Left Ventricular Assist Device by the Use of Sublingual Microcirculatory Imaging: A New Diagnostic Imaging Tool?

Clinical diagnosis of cardiac tamponade can be difficult in patients with continuous flow left ventricle assist devices (cf-LVADs). This is even more so because of the lack of adequate bedside echocardiographic windows. Previous studies on monitoring sublingual microcirculation showed deterioration of end-organ perfusion in patient with cardiogenic shock. In this paper we report alterations in the sublingual microcirculation in a cf-LVAD patient prior to clinical manifestation of tamponade. Our case report suggests that such real-time monitoring of the microcirculation may provide a new diagnostic modality for early recognition of cardiac tamponade.

Temporary Right-Ventricular Assist Devices: A Systematic Review.

Acute right-sided heart failure (RHF) is a complex clinical syndrome, with a wide range of clinical presentations, associated with increased mortality and morbidity, but about which there is a scarcity of evidence-based literature. A temporary right-ventricular assist device (t-RVAD) is a potential treatment option for selected patients with severe right-ventricular dysfunction as a bridge-to-recovery or as a permanent solution. We sought to conduct a systematic review to determine the safety and efficacy of t-RVAD implantation. Thirty-one studies met the inclusion criteria, from which data were extracted. Successful t-RVAD weaning ranged between 23% and 100%. Moreover, 30-day survival post-temporary RAVD implantation ranged from 46% to 100%. Bleeding, acute kidney injury, stroke, and device malfunction were the most commonly reported complications. Notwithstanding this, t-RVAD is a lifesaving option for patients with severe RHF, but the evidence stems from small non-randomized heterogeneous studies utilizing a variety of devices. Both the etiology of RHF and time of intervention might play a major role in determining the t-RVAD outcome. Standardized endpoints definitions, design and methodology for t-RVAD trials is needed. Furthermore, efforts should continue in improving the technology as well as improving the timely provision of a t-RVAD.

A low aldosterone/renin ratio and high soluble ACE2 associate with COVID-19 severity.

BACKGROUND: The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered well tolerated. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2. METHODS: Adult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma) and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. MEASUREMENTS AND MAIN RESULTS: Out of the 188 patients who were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. CONCLUSION: High sACE2, a low aldosterone/renin ratio and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. TRIAL REGISTRATION: retrospectively registered.

Kidney Microcirculation as a Target for Innovative Therapies in AKI.

Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of function and damage. The renal microcirculation plays a crucial role in maintaining the kidney's functional and structural integrity for oxygen and nutrient supply and waste product removal. However, alterations in microcirculation and oxygenation due to renal perfusion defects, hypoxia, renal tubular, and endothelial damage can result in AKI and the loss of renal function regardless of systemic hemodynamic changes. The unique structural organization of the renal microvasculature and the presence of autoregulation make it difficult to understand the mechanisms and the occurrence of AKI following disorders such as septic, hemorrhagic, or cardiogenic shock; ischemia/reperfusion; chronic heart failure; cardiorenal syndrome; and hemodilution. In this review, we describe the organization of microcirculation, autoregulation, and pathophysiological alterations leading to AKI. We then suggest innovative therapies focused on the protection of the renal microcirculation and oxygenation to prevent AKI.

Veno-arterial thrombosis and microcirculation imaging in a patient with COVID-19.

The Coronavirus pandemic has brought new challenges in intensive care medicine. Understanding of the pathophysiology of the vascular complications of SARS-CoV-2 infection could bring new resuscitation and therapeutic options. In this case report, we present a patient with COVID-19 pneumonia, who was admitted to our ICU and treated with high-flow nasal cannula, dexamethasone, remdesivir and high-dose prophylactic low molecular weight heparin. During ICU admission, substantial venous and arterial thrombosis developed. Meanwhile the microcirculation showed more than double amount of organ perfusion with very high total vessel density. We hypothesize that this might be a compensatory mechanism for the generalized prothrombic state in which the microcirculation increases the oxygen extraction capacity preventing multi-organ failure.

Myasthenic crisis-induced Takotsubo cardiomyopathy in an elderly man: A case report of an underestimated but deadly combination.

BACKGROUND: Patients with myasthenia gravis (MG) are at a higher risk of developing Takotsubo cardiomyopathy (TTC), particularly during a myasthenic crisis. Myasthenic crisis-associated TTC occurs predominantly in women. In this case report, we present a man with metastasized prostate carcinoma who developed TTC after new-onset MG. CASE SUMMARY: An 81-year-old man with non-insulin dependent diabetes mellitus and metastasized prostate carcinoma presented with dyspnea. During primary assessment examination at the emergency department, there was evident blepharoptosis of his right eye. His electrocardiograms were suggestive of an acute anterior wall myocardial infarction, for which he underwent emergency coronary angiography. No obstructive coronary artery disease was found. During the coronary angiography, the patient developed respiratory failure and was admitted to the Intensive Care Unit for non-invasive respiratory support. The following day, diagnostic neostigmine test revealed a myasthenic crisis. Bedside echocardiography revealed left ventricular apical ballooning with a typical appearance of TTC. Despite the potentially reversible character of both MG and TTC, the patient and family requested an end of support in the Intensive Care Unit due to age and chronic malignancy with reduced quality of life in recent months after non-chemo-responding prostate carcinoma. The patient died soon after treatment withdrawal. CONCLUSION: Elderly men should be carefully evaluated for TTC when new-onset MG is diagnosed.

Capillary Leukocytes, Microaggregates, and the Response to Hypoxemia in the Microcirculation of Coronavirus Disease 2019 Patients.

OBJECTIVES: In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN: Multicenter case-controlled study. SETTING: Two ICUs in The Netherlands and one in Switzerland. PATIENTS: Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculatory parameters quantified included total vessel density (mm × mm-2), functional capillary density (mm × mm-2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (µm × s-1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s-1) and capillary RBC microaggregates (4 s-1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers. CONCLUSIONS: The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.

Microcirculatory Response to Blood vs. Crystalloid Cardioplegia During Coronary Artery Bypass Grafting With Cardiopulmonary Bypass.

Background: Blood cardioplegia attenuates cardiopulmonary bypass (CPB)-induced systemic inflammatory response in patients undergoing cardiac surgery, which may favorably influence the microvascular system in this cohort. The aim of this study was to investigate whether blood cardioplegia would offer advantages over crystalloid cardioplegia in the preservation of microcirculation in patients undergoing coronary artery bypass grafting (CABG) with CPB. Methods: In this prospective observational cohort study, 20 patients who received crystalloid (n = 10) or blood cardioplegia (n = 10) were analyzed. The microcirculatory measurements were obtained sublingually using incident dark-field imaging at five time points ranging from the induction of anesthesia (T0) to discontinuation of CPB (T5). Results: In the both crystalloid [crystalloid cardioplegia group (CCG)] and blood cardioplegia [blood cardioplegia group (BCG)] groups, perfused vessel density (PVD), total vessel density (TVD), and proportion of perfused vessels (PPV) were reduced after the beginning of CPB. The observed reduction in microcirculatory parameters during CPB was only restored in patients who received blood cardioplegia and increased to baseline levels as demonstrated by the percentage changes from T0 to T5 (%Δ)T0-T5 in all the functional microcirculatory parameters [%ΔTVDT0-T5(CCG): -10.86 ± 2.323 vs. %ΔTVDT0-T5(BCG): 0.0804 ± 1.107, p < 0.001; %ΔPVDT0-T5(CCG): -12.91 ± 2.884 vs. %ΔPVDT0-T5(BCG): 1.528 ± 1.144, p < 0.001; %ΔPPVT0-T5(CCG): -2.345 ± 1.049 vs. %ΔPPVT0-T5(BCG): 1.482 ± 0.576, p < 0.01]. Conclusion: Blood cardioplegia ameliorates CPB-induced microcirculatory alterations better than crystalloid cardioplegia in patients undergoing CABG, which may reflect attenuation of the systemic inflammatory response. Future investigations are needed to identify the underlying mechanisms of the beneficial effects of blood cardioplegia on microcirculation.

Evaluation of patients with a HeartMate 3 left ventricular assist device using echocardiographic particle image velocimetry.

PURPOSE: Poor left ventricular (LV) function may affect the physiological intraventricular blood flow and physiological vortex formation. The aim of this study was to investigate the pattern of intraventricular blood flow dynamics in patients with LV assist devices (LVADs) using echocardiographic particle image velocimetry. MATERIALS AND METHODS: This prospective study included 17 patients (mean age 57 ± 11 years, 82% male) who had received an LVAD (HeartMate 3, Abbott Laboratories, Chicago, Illinois, USA) because of end-stage heart failure and poor LV function. Eleven (64%) patients had ischemic cardiomyopathy, and six patients (36%) had nonischemic cardiomyopathy. All patients underwent echocardiography, including intravenous administration of an ultrasound-enhancing agent (SonoVue, Bracco, Milan, Italy). Echocardiographic particle image velocimetry was used to quantify LV blood flow dynamics, including vortex formation (Hyperflow software, Tomtec imaging systems Gmbh, Unterschleissheim, Germany). RESULTS: Contrast-enhanced ultrasound was well tolerated in all patients and was performed without adverse reactions or side effects. The LVAD function parameters did not change during or after the ultrasound examination. The LVAD flow was on average 4.3 ± 0.3 L/min, and the speed was 5247 ± 109 rotations/min. The quantification of LV intraventricular flow demonstrated substantial impairment of vortex parameters. The energy dissipation, vorticity, and kinetic energy fluctuation indices were severely impaired. CONCLUSIONS: Echo particle velocimetry is safe and feasible for the quantitative assessment of intraventricular flow in patients with an LVAD. The intraventricular LV flow and vortex parameters are severely impaired in these patients.

Automated Algorithm Analysis of Sublingual Microcirculation in an International Multicentral Database Identifies Alterations Associated With Disease and Mechanism of Resuscitation.

OBJECTIVES: Reliable automated handheld vital microscopy image sequence analysis and the identification of disease states and effects of therapy are prerequisites for the routine use of quantitative sublingual microcirculation measurements at the point-of-care. The present study aimed to clinically validate the recently introduced MicroTools software in a large multicentral database of perioperative and critically ill patients and to use this automatic algorithm to data-mine and identify the sublingual microcirculatory variable changes in response to disease and therapy. DESIGN: Retrospective algorithm-based image analysis and data-mining within a large international database of sublingual capillary microscopy. Algorithm-based analysis was compared with manual analysis for validation. Thereafter, MicroTools was used to identify the functional microcirculatory alterations associated with disease conditions and identify therapeutic options for recruiting functional microcirculatory variables. SETTING: Ten perioperative/ICU/volunteer studies in six international teaching hospitals. PATIENTS: The database encompass 267 adult and pediatric patients undergoing surgery, treatment for sepsis, and heart failure in the ICU and healthy volunteers. INTERVENTIONS: Perioperative and ICU standard of care. MEASUREMENTS AND MAIN RESULTS: One thousand five hundred twenty-five handheld vital microscopy image sequences containing 149,257 microscopy images were analyzed. 3.89 × 10 RBC positions were tracked by the algorithm in real time, and offline manual analysis was performed. Good correlation and trending ability were found between manual and automatic total and functional capillary density (r = 0.6-0.8; p < 0.0001). RBC tracking within the database demonstrated changes in functional capillary density and/or RBC velocity in septic shock, heart failure, hypovolemia, obstructive shock, and hemodilution and thus detected the presence of a disease condition. Therapies recruiting the microcirculatory diffusion and convection capacity associated with systemic vasodilation and an increase in cardiac output were separately identified. CONCLUSIONS: Algorithm-based analysis of the sublingual microcirculation closely matched manual analysis across a broad spectrum of populations. It successfully identified a methodology to quantify microcirculatory alterations associated with disease and the success of capillary recruitment, improving point-of-care application of microcirculatory-targeted resuscitation procedures.

Causes and predictors of early mortality in patients treated with left ventricular assist device implantation in the European Registry of Mechanical Circulatory Support (EUROMACS).

PURPOSE: The aim of the study was to analyze early mortality after continuous-flow left ventricular assist device (LVAD) implantation which remains high. METHODS: We analyzed consecutive (n = 2689) patients from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) undergoing continuous-flow LVAD implantation. The primary outcome was early (< 90 days) mortality. Secondary outcomes were differential causes of early post-operative death following LVAD implantation. RESULTS: Univariable and multivariable analysis as well as regression analysis were used to examine determinants and differential causes of early (< 90 days) mortality after LVAD implantation. During the first 90 days, 2160 (80%) patients were alive with ongoing LVAD support, 40(2%) patients underwent heart transplantation, and 487(18%) deceased. The main causes of early death were MOF (36%), sepsis (28%), cardiopulmonary failure (CPF; 10%), CVA (9%), and right-sided heart failure (RHF, 8%). Furthermore, MOF and sepsis are 70% of causes of death in the first week. Independent clinical predictors of early death were age, female sex, INTERMACS profile 1 to 3, and ECMO. Laboratory predictors included elevated serum creatinine, total bilirubin, lactate, and low hemoglobin. Furthermore, hemodynamic predictors included elevated RA-to-PCWP ratio, pulmonary vascular resistance, and low systemic vascular resistance. Longer total implantation time was also independent predictor of early mortality. A simple model of 12 variables predicts early mortality following LVAD implantation with a good discriminative power with area under the curve of 0.75. CONCLUSIONS: In the EUROMACS registry, approximately one out of five patients die within 90 days after LVAD implantation. Early mortality is primarily dominated by multiorgan failure followed by sepsis. A simple model identifies important parameters which are associated with early mortality following LVAD implantation.