ARNI Pre-Operative Use and Vasoplegic Syndrome in Patients Undergoing Heart Transplantation or Left Ventricular Assist Device Surgery

Background: Vasoplegic syndrome after orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation is a rare but highly lethal syndrome with complex etiologies. The objective of this study was to assess if the preoperative use of sacubitril-valsartan combination is associated with an increased vasoplegic syndrome (VS) frequency after OHT or LVAD implantation and its relationship with 30-day mortality. Methods: A retrospective review of perioperative data, between January 2016 and December 2017, from 73 consecutive OHT and LVAD surgery adult patients at our institution was performed. VS was defined as normal cardiac output with persistent low systemic resistance requiring a norepinephrine intravenous perfusion > 0.5 µg/kg/min and the absence of sepsis or hemorrhagic shock within 48 h after surgery. Patients were all followed-up for adverse events and all-cause mortality at 30 days. Results: In our cohort of 73 patients (median age 51.7 years, 65% male patients), 25 (34%) patients developed VS. Twenty-two (30.1%) patients were on ARNI at the time of surgery, 31 (42.5%) were on other RAS blockers, 12 (16.4%) were on norepinephrine and 8 (11%) had no pre-operative drug. The pre-operative use of any vasoactive agent, was not significantly associated with VS (OR = 1.36; IC95% [0.78; 2.35]; p = 0.38). The pre-operative use of an ARNI compared to all other groups was not significantly associated with VS (OR = 2.0; IC95% [0.71; 5.62]; p = 0.19). The pre-operative use of an ARNI compared to other RAS blockers was also not significantly associated with VS (OR = 1.25; IC95% [0.37; 4.26]; p = 0.72). At 30 days, 18 (24.7%) patients had died. The pre-operative treatment with ARNI, or other RAS inhibitors was associated with a significantly lower rate of death compared to the absence of treatment (HR = 0.11; IC95% [0.02; 0.55]; p = 0.009 for ARNI and HR = 0.20; IC95% [0.06; 0.69]; p = 0.011 for other RASi). Conclusions: Preoperative use of sacubitril-valsartan was not significantly associated with development of vasoplegic syndrome in patients undergoing OHT or LVAD surgery. Furthermore, our data suggests a significant 30-day survival benefit with efficient renin-angiotensin blockade before surgery.

Hemodynamic and Metabolic Tolerance of Acetate-Free Biofiltration in Mechanically Ventilated Critically Ill Patients: A Real-Life Study

Intradialytic hypotension can lead to superimposed organ hypoperfusion and ultimately worsens long-term kidney outcomes in critically ill patients requiring kidney replacement therapy. Acetate-free biofiltration (AFB), an alternative technique to bicarbonate-based hemodialysis (B-IHD) that does not require dialysate acidification, may improve hemodynamic and metabolic tolerance of dialysis. In this study, we included 49 mechanically ventilated patients requiring 4 h dialysis (AFB sessions n = 66; B-IHD sessions n = 62). Whereas more AFB sessions were performed in patients at risk of hemodynamic intolerance, episodes of intradialytic hypotension were significantly less frequent during AFB compared to B-IHD, whatever the classification used (decrease in mean blood pressure ≥ 10 mmHg; systolic blood pressure decrease >20 mmHg or absolute value below 95 mmHg) and after adjustment on the use of vasoactive agent. Diastolic blood pressure readily increased throughout the dialysis session. The use of a bicarbonate zero dialysate allowed the removal of 113 ± 25 mL/min of CO2 by the hemofilter. After bicarbonate reinjection, the global CO2 load induced by AFB was +25 ± 6 compared to +80 ± 12 mL/min with B-IHD (p = 0.0002). Thus, notwithstanding the non-controlled design of this study, hemodynamic tolerance of AFB appears superior to B-IHD in mechanically ventilated patients. Its use as a platform for CO2 removal also warrants further research.

Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study

Background Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. Methods All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. Results Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. Conclusions Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.

Early postoperative hemodynamic instability after heart transplantation – incidence and metabolic indicators

Background Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study’s primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon. Methods Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) < 60 mmHg) combined with a high inotrope score (> 10). Data for long-term mortality were obtained from the population registration office. Results PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) μg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) μg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034). Conclusions Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients.

Is the Exposome Involved in Brain Disorders through the Serotoninergic System?

Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine acting as a neurotransmitter in the central nervous system (CNS), local mediator in the gut, and vasoactive agent in the blood. It has been linked to a variety of CNS functions and is implicated in many CNS and psychiatric disorders. The high comorbidity between some neuropathies can be partially understood by the fact that these diseases share a common etiology involving the serotoninergic system. In addition to its well-known functions, serotonin has been shown to be a mitogenic factor for a wide range of normal and tumor cells, including glioma cells, in vitro. The developing CNS of fetus and newborn is particularly susceptible to the deleterious effects of neurotoxic substances in our environment, and perinatal exposure could result in the later development of diseases, a hypothesis known as the developmental origin of health and disease. Some of these substances affect the serotoninergic system and could therefore be the source of a silent pandemic of neurodevelopmental toxicity. This review presents the available data that are contributing to the appreciation of the effects of the exposome on the serotoninergic system and their potential link with brain pathologies (neurodevelopmental, neurodegenerative, neurobehavioral disorders, and glioblastoma).

Postoperative Blood Pressure and Heart Rate Alterations After Carotid Body Tumor Excision: A Retrospective Study of 108 Cases

Background Arising from chemoreceptor cells, carotid body tumors (CBTs) are rare neoplasms associated with hemodynamics. Postoperative changes in blood pressure (BP) and heart rate (HR) are not completely understood. Methods This retrospective, observational, controlled study included all CBT patients from 2013 to 2018 in Peking Union Medical College Hospital. Postoperative changes in BP/HR within or between unilateral/bilateral/control groups were investigated. Perioperative details across Shamblin types were also assessed. Results This study included 108 patients (116 excised CBTs). The postoperative systolic BP and HR increased in both unilateral and bilateral CBT patients compared with the preoperative measures. Compared with control group, the postoperative systolic BP increased (difference in the alteration = 6.3, 95% CI 3.5 ~ 9.0, p < 0.001) in unilateral CBT patients; both systolic BP (difference in the alteration = 9.2, 95% CI 1.1 ~ 17.3, p = 0.027) and HR (difference in the alteration = 5.3, 95% CI 1.0 ~ 9.6, p = 0.016) increased in bilateral CBT patients. More CBT patients required extra antihypertensive therapy after surgery than controls (OR = 2.5, 95% CI 1.14 ~ 5.5, p = 0.024). Maximum tumor diameter, intraoperative vascular injury, continuous vasoactive agent requirement, total fluid volume/transfusion, estimated blood loss, operation duration, postoperative pathology, overall complications, and intensive care unit/hospital lengths of stay significantly varied among Shamblin types. Conclusions CBT excision may be associated with subtle postoperative hemodynamic changes. Perioperative management of CBT patients necessitates careful assessment, full preparation and close postoperative monitoring.

Measuring Cerebrovascular Reactivity: Sixteen Avoidable Pitfalls

An increase in arterial PCO2 is the most common stressor used to increase cerebral blood flow for assessing cerebral vascular reactivity (CVR). That CO2 is readily obtained, inexpensive, easy to administer, and safe to inhale belies the difficulties in extracting scientifically and clinically relevant information from the resulting flow responses. Over the past two decades, we have studied more than 2,000 individuals, most with cervical and cerebral vascular pathology using CO2 as the vasoactive agent and blood oxygen-level-dependent magnetic resonance imaging signal as the flow surrogate. The ability to deliver different forms of precise hypercapnic stimuli enabled systematic exploration of the blood flow-related signal changes. We learned the effect on CVR of particular aspects of the stimulus such as the arterial partial pressure of oxygen, the baseline PCO2, and the magnitude, rate, and pattern of its change. Similarly, we learned to interpret aspects of the flow response such as its magnitude, and the speed and direction of change. Finally, we were able to test whether the response falls into a normal range. Here, we present a review of our accumulated insight as 16 “lessons learned.” We hope many of these insights are sufficiently general to apply to a range of types of CO2-based vasoactive stimuli and perfusion metrics used for CVR.

Serum IL-27 Predicts the Severity and Prognosis in Patients With Community-acquired Pneumonia: A Prospective Cohort Study

Background: The previous studies have revealed that IL-27 was involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of IL-27 in the community-acquired pneumonia (CAP) was unclear. The goal of this research was to explore the associations of serum IL-27 with the severity and prognosis among CAP patients through a prospective cohort study.Methods: The whole of 239 healthy population and 239 CAP patients were enrolled. Fasting blood samples were collected. Inflammatory cytokines were detected using enzyme linked immunosorbent assay (ELISA). Demographic characteristics and clinical information were analyzed. Results: Serum IL-27 was significantly risen in CAP patients compared with control subjects on admission. Besides, serum IL-27 was gradually increased in line with CAP severity scores among CAP patients. Analysis on relevance suggested that serum IL-27 was associated with blood routine indices, renal function, liver function, myocardial function and inflammatory cytokines. Linear regression and logistic regression revealed that serum IL-27 was positively correlated with CAP severity scores. Logistic regression demonstrated that serum IL-27 on admission was positively correlated with vasoactive agent usage and longer hospital stay during hospitalization among CAPO patients. Conclusions: Serum IL-27 is markedly and positively associated with the severity and poor prognosis among CAP patients, indicating that IL-27 may involve in the pathophysiological process of CAP. Serum IL-27 may be used as a diagnostic and prognostic biomarker for CAP patients.

Risk Factors for Noninvasive Ventilation Failure in Children Post-Hematopoietic Cell Transplant

RationaleLittle is known on the use of noninvasive ventilation (NIPPV) in pediatric hematopoietic cell transplant (HCT) patients.ObjectiveWe sought to describe the landscape of NIPPV use and to identify risk factors for failure to inform future investigation or quality improvement.MethodsThis is a multicenter, retrospective observational cohort of 153 consecutive children post-HCT requiring NIPPV from 2010-2016.Results97 (63%) failed NIPPV. Factors associated with failure on univariate analysis included: longer oxygen use prior to NIPPV (p=0.04), vasoactive agent use (p&lt;0.001), and higher respiratory rate at multiple hours of NIPPV use (1hr p=0.02, 2hr p=0.04, 4hr p=0.008, 8hr p=0.002). Using respiratory rate at 4 hours a multivariable model was constructed. This model demonstrated high ability to discriminate NIPPV failure (AUC=0.794) with the following results: respiratory rate &gt;40 at 4 hours [aOR=6.3 9(95% CI: 2.4, 16.4), p&lt;0.001] and vasoactive use [aOR=4.9 (95% CI: 1.9, 13.1), p=0.001]. Of note, 11 patients had a cardiac arrest during intubation (11%) and 3 others arrested prior to intubation. These 14 patients were closer to HCT [14 days (IQR:4, 73) vs 54 (IQR:21,117), p&lt;0.01] and there was a trend toward beginning NIPPV outside of the PICU and arrest during/prior to intubation (p=0.056).ConclusionsIn this cohort respiratory rate at 4 hours and vasoactive use are independent risk factors of NIPPV failure. An objective model to predict which children may benefit from a trial of NIPPV, may also inform the timing of both NIPPV initiation and uncomplicated intubation.

Acute coronary syndrome in COVID-19 patients. Clinical features, severity and outcomes. Results from Spanish multicenter registry Car-COVID19

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fundación del Corazón Introduction COVID19 has spread uncontrollably all over the world through this 2020 year. As a new entity, we did not know the potential cardiovascular manifestations of this infectious disease. This national registry was created to describe the cardiac affection and its severity. Methods and results A multicenter registry was conducted, including 28 centers in Spain. Patients with COVID19 diagnosis presenting an acute cardiovascular event between March 1st and May 30th were included. Eighty-two patients were included. Of them, 49 (76,6%) presented with acute coronary syndrome; the rest were diagnosed of acute myocarditis or stress cardiomyopathy. The majority of cases were STEMI (n = 31), while the remaining 35,4% presented as NSTEMI. 29 patients (61,7%) underwent emergent percutaneous coronary intervention (PCI) (Figure 1). Anterior (n = 18) and inferior (n = 16) were the most frequent locations. Coronary angiogram showed total occlusion in 20 patients (55,6%); while 7 patients presented with non-obstructive coronary arteries. PCI was done in 31 patients. Eight patients (17,8%) developed Killip III-IV myocardial infarction. A total of 10 patients required endotracheal intubation and vasoactive agent were needed in 11 patients; none required IABP or ECMO. In-hospital mortality rate was 26,2%. Conclusions Patients with COVID19 may present with acute coronary syndromes. This entity has a poor prognosis, with noteworthy mortality. Table 1. Baseline characteristics.n (%)Age69,0[63,0-76,5]Sex (female)9 (19,1%)Hypertension28 (57,1%)Dyslipidemia25 (51,0%)Diabetes mellitus11 (22,4%)Chronic coronary disease10 (20,4%)Previous PCI10 (20,4%)Previous CABG0Previous AAS15 (30,6%)Smoking10 (20,4%)PCI percutaneous coronary intervention; CABG: coronary artery bypass graft; AAS: aspirin.Abstract Figure 1.