Vagal sensory neurons mediate the Bezold-Jarisch reflex and induce syncope.

Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders1. The Bezold-Jarisch reflex (BJR), first described2,3 in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing4 to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses-hypotension, bradycardia and suppressed respiration-and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push-pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels.

Circulatory trajectories after out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Circulatory failure frequently occurs after out-of-hospital cardiac arrest (OHCA) and is part of post-cardiac arrest syndrome (PCAS). The aim of this study was to investigate circulatory disturbances in PCAS by assessing the circulatory trajectory during treatment in the intensive care unit (ICU). METHODS: This was a prospective single-center observational cohort study of patients after OHCA. Circulation was continuously and invasively monitored from the time of admission through the following five days. Every hour, patients were classified into one of three predefined circulatory states, yielding a longitudinal sequence of states for each patient. We used sequence analysis to describe the overall circulatory development and to identify clusters of patients with similar circulatory trajectories. We used ordered logistic regression to identify predictors for cluster membership. RESULTS: Among 71 patients admitted to the ICU after OHCA during the study period, 50 were included in the study. The overall circulatory development after OHCA was two-phased. Low cardiac output (CO) and high systemic vascular resistance (SVR) characterized the initial phase, whereas high CO and low SVR characterized the later phase. Most patients were stabilized with respect to circulatory state within 72 h after cardiac arrest. We identified four clusters of circulatory trajectories. Initial shockable cardiac rhythm was associated with a favorable circulatory trajectory, whereas low base excess at admission was associated with an unfavorable circulatory trajectory. CONCLUSION: Circulatory failure after OHCA exhibits time-dependent characteristics. We identified four distinct circulatory trajectories and their characteristics. These findings may guide clinical support for circulatory failure after OHCA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061.

Impact of Acute and Chronic Hypoxia-Ischemia on the Transitional Circulation.

The transition from intrauterine life to extrauterine existence encompasses significant cardiorespiratory adaptations. These include rapid lung aeration and increase in pulmonary blood flow (PBF). Perinatal asphyxia and fetal growth restriction can severely hamper this transition. Hypoxia is the common denominator in these 2 disease states, with the former characterized by acute insult and the latter by utero-placental insufficiency and a chronic hypoxemic state. Both may manifest as hemodynamic instability. In this review, we emphasize the role of physiologic-based cord clamping in supplementing PBF during transition. The critical role of lung aeration in initiating pulmonary gas exchange and increasing PBF is discussed. Physiologic studies in animal models have enabled greater understanding of the mechanisms and effects of various therapies on transitional circulation. With data from sheep models, we elaborate instrumentation for monitoring of cardiovascular and pulmonary physiology and discuss the combined effect of chest compressions and adrenaline in improving transition at birth. Lastly, physiologic adaptation influencing management in human neonatal cohorts with respect to cardiac and vascular impairments in hypoxic-ischemic encephalopathy and growth restriction is discussed. Impairments in right ventricular function and vascular mechanics hold the key to prognostication and understanding of therapeutic rationale in these critically ill cohorts. The right ventricle and pulmonary circulation seem to be especially affected and may be explored as therapeutic targets. The role of comprehensive assessments using targeted neonatal echocardiography as a longitudinal, reliable, and easily accessible tool, enabling precision medicine facilitating physiologically appropriate treatment choices, is discussed.

Association between In-hospital Mortality and Low Cardiac Output Syndrome with Morning versus Afternoon Cardiac Surgery.

BACKGROUND: Recent work suggests that having aortic valve surgery in the morning increases risk for cardiac-related complications. This study therefore explored whether mortality and cardiac complications, specifically low cardiac output syndrome, differ for morning and afternoon cardiac surgeries. METHODS: The study included adults who had aortic and/or mitral valve repair/replacement and/or coronary artery bypass grafting from 2011 to 2018. The components of the in-hospital composite outcome were in-hospital mortality and low cardiac output syndrome, defined by requirement for at least two inotropic agents at 24 to 48 h postoperatively or need for mechanical circulatory support. Patients who had aortic cross-clamping between 8 and 11 am (morning surgery) versus between 2 and 5 pm (afternoon surgery) were compared on the incidence of the composite outcome. RESULTS: Among 9,734 qualifying operations, 0.4% (29 of 6,859) died after morning, and 0.7% (20 of 2,875) died after afternoon surgery. The composite of in-hospital mortality and low cardiac output syndrome occurred in 2.8% (195 of 6,859) of morning patients and 3.4% (97 of 2,875) of afternoon patients: morning versus afternoon confounder-adjusted odds ratio, 0.96 (95% CI, 0.75 to 1.24; P = 0.770). There was no evidence of interaction between morning versus afternoon and surgery type (P = 0.965), and operation time was statistically nonsignificant for surgery subgroups. CONCLUSIONS: Patients having aortic valve surgery, mitral valve surgery, and/or coronary artery bypass grafting with aortic cross-clamping in the morning and afternoon did not have significantly different outcomes. No evidence was found to suggest that morning or afternoon surgical timing alters postoperative risk.

A Randomized Porcine Study in Low Cardiac Output of Vasoactive and Inotropic Drug Effects on the Gastrointestinal Tract.

BACKGROUND: Splanchnic vasodilation by inodilators is an argument for their use in critical cardiac dysfunction. To isolate peripheral vasoactivity from inotropy, such drugs were investigated, and contrasted to vasopressors, in a fixed low cardiac output (CO) model resembling acute cardiac dysfunction effects on the gastrointestinal tract. We hypothesized that inodilators would vasodilate and preserve the aerobic metabolism in the splanchnic circulation in low CO. METHODS: In anesthetized pigs, CO was lowered to 60% of baseline by partial inferior caval vein balloon inflation. The animals were randomized to placebo (n = 8), levosimendan (24 µg kg-1 bolus, 0.2 µg kg-1 min-1, n = 7), milrinone (50 µg kg-1 bolus, 0.5 µg kg-1 min-1, n = 7), vasopressin (0.001, 0.002 and 0.006 U kg-1 min-1, 1 h each, n = 7) or norepinephrine (0.04, 0.12, and 0.36 µg kg-1 min-1, 1 h each, n = 7). Hemodynamic variables including mesenteric blood flow were collected. Systemic, mixed-venous, mesenteric-venous, and intraperitoneal metabolites were analyzed. RESULTS: Cardiac output was stable at 60% in all groups, which resulted in systemic hypotension, low superior mesenteric artery blood flow, lactic acidosis, and increased intraperitoneal concentrations of lactate. Levosimendan and milrinone did not change any circulatory variables, but levosimendan increased blood lactate concentrations. Vasopressin and norepinephrine increased systemic and mesenteric vascular resistances at the highest dose. Vasopressin increased mesenteric resistance more than systemic, and the intraperitoneal lactate concentration and lactate/pyruvate ratio. CONCLUSION: Splanchnic vasodilation by levosimendan and milrinone may be negligible in low CO, thus rejecting the hypothesis. High-dose vasopressors may have side effects in the splanchnic circulation.

Interventions Associated With Treatment of Low Cardiac Output After Stage 1 Norwood Palliation.

BACKGROUND: Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Both cardiac output (CO) and systemic vascular resistance (SVR) contribute to hemodynamic vulnerability. Simultaneous measures of mean arterial pressure and somatic regional near infrared spectroscopy saturation can classify complex hemodynamics into 4 distinct states, with a low-CO state of higher risk. We sought to identify interventions associated with low-CO state occupancy and transition. METHODS: Perioperative data were prospectively collected in an institutional review board-approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis. Associations of static and dynamic support levels and state classifications over 48 postoperative hours were tested between states and across transitions using mixed regression methods in a quasi-experimental design. RESULTS: Data from 10,272 hours in 214 patients were analyzed. A low-CO state was observed in 142 patients for 1107 hours. Both low CO and extracorporeal membrane oxygenation had increased mortality risk. The low-CO state was characterized by lower milrinone but higher catecholamine dose. Successful transition out of low CO was associated with increased milrinone dose and hemoglobin concentration. Increasing milrinone and hemoglobin levels predicted reduced risk of low CO in future states. CONCLUSIONS: Bivariate classification objectively defines hemodynamic states and transitions with distinct support profiles. Maintaining or increasing inodilator and hemoglobin levels were associated with improved hemodynamic conditions and were predictive of successful future transitions from the low-CO state.

Predictors of low exercise cardiac output in patients with severe pulmonic regurgitation.

BACKGROUND AND OBJECTIVES: Chronic pulmonic regurgitation (PR) following repair of congenital heart disease (CHD) impairs right ventricular function that impacts peak exercise cardiac index (pCI). We aimed to estimate in a non-invasive way pCI and peak oxygen consumption (pVO2) and to evaluate predictors of low pCI in patients with significant residual pulmonic regurgitation after CHD repair. METHOD: We included 82 patients (median age 19 years (range 10-54 years)) with residual pulmonic regurgitation fraction >40%. All underwent cardiac MRI and cardiopulmonary testing with measurement of pCI by thoracic impedancemetry. Low pCI was defined <7 L/min/m2. RESULTS: Low pCI was found in 18/82 patients. Peak indexed stroke volume (pSVi) tended to compensate chronotropic insufficiency only in patients with normal pCI (r=-0.31, p=0.01). Below 20 years of age, only 5/45 patients had low pCI but near-normal (≥6.5 L/min/m2). pVO2 (mL/kg/min) was correlated with pCI (r=0.58, p=0.0002) only in patients aged >20 years. Left ventricular stroke volume in MRI correlated with pSVi only in the group of patients with low pCI (r=0.54, p=0.02). No MRI measurements predicted low pCI. In multivariable analysis, only age predicted a low pCI (OR=1.082, 95% CI 1.035 to 1.131, p=0.001) with continuous increase of risk with age. CONCLUSIONS: In patients with severe PR, pVO2 is a partial reflection of pCI. Risk of low pCI increases with age. No resting MRI measurement predicts low haemodynamic response to exercise. Probably more suitable to detect ventricular dysfunction, pCI measurement could be an additional parameter to take into account when considering pulmonic valve replacement.

Semi-urgent pulmonary vein isolation using cryoballoon for haemodynamically unstable atrial fibrillation storm in a patient with low cardiac output syndrome: a case report.

BACKGROUND: Atrial fibrillation and heart failure are common coexisting conditions requiring hospitalisation for heart failure and death. Pulmonary vein isolation is a well-established option for symptomatic atrial fibrillation and for atrial fibrillation concomitant with heart failure with reduced left ventricular ejection fraction. Recently, pulmonary vein isolation using cryoballoon showed non-inferiority to radiofrequency ablation with respect to the treatment of patients with drug-refractory paroxysmal atrial fibrillation. However, the effectiveness of acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon in patients with haemodynamically unstable atrial fibrillation storm accompanied with low cardiac output syndrome is unclear. Herein, we present a case in which semi-urgent pulmonary vein isolation using cryoballoon was effective for acute-phase rhythm control against drug-resistant and haemodynamically unstable repetitive atrial fibrillation tachycardia accompanied with low cardiac output syndrome. CASE PRESENTATION: A 57-year-old man was hospitalised for New York Heart Association functional class 4 heart failure with atrial fibrillation tachycardia and reduced left ventricular ejection fraction of 20% accompanied with low cardiac output syndrome-induced liver damage. The haemodynamics collapsed during atrial fibrillation tachycardia, which had become resistant to intravenous amiodarone and repeated electrical cardioversions. In addition to atrial fibrillation, atrial tachycardia and common-type atrial flutter appeared on day 3. Multiple organ failure progressed gradually due to haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome. On day 4, to focus on treatment of heart failure and multiple organ failure, semi-urgent rescue pulmonary vein isolation using cryoballoon to atrial fibrillation and cavotricuspid isthmus ablation to common-type atrial flutter were performed for acute-phase rhythm control. Soon after the ablation procedure, atrial fibrillation and common-type atrial flutter were lessened, and sinus rhythm was restored. A stable haemodynamics was successfully achieved with the improvement of hepatorenal function. The patient was discharged on day 77 without complications. CONCLUSIONS: This case demonstrates that acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon could be a treatment option in patients with haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome, which is refractory to cardioversion and drug therapy.

Volume-associated hemodynamic variables for prediction of cardiac surgery-associated acute kidney injury.

BACKGROUND: Delayed diagnosis of acute kidney injury (AKI) is common because the changes in renal function markers often lag injury. We aimed to find optimal non-invasive hemodynamic variables for the prediction of postoperative AKI and AKI renal replacement therapy (RRT). METHODS: The data were collected from 1,180 patients who underwent cardiac surgery in our hospital between March 2015 and Feb 2016. Postoperative central venous pressure (CVP), mean arterial pressure (MAP), heart rate, PaO2, and PaCO2 on ICU admission and daily fluid input and output (calculated as 24 h PFO) were monitored and compared between AKI vs. non-AKI and RRT vs non-RRT cases. RESULTS: The AKI and AKI-RRT incidences were 36.7% (n = 433) and 1.2% (n = 14). Low cardiac output syndromes (LCOSs) occurred significantly more in AKI and RRT than in non-AKI or non-RRT groups (13.2% vs. 3.9%, P < 0.01; 42.9% vs. 7.1%, P < 0.01). CVP on ICU admission was significantly higher in AKI and RRT than in non-AKI and non-RRT groups (11.5 vs. 9.0 mmHg, P < 0.01; 13.3 vs. 9.9 mmHg, P < 0.01). 24 h PFO in AKI and RRT cases were significantly higher than in non-AKI or non-RRT patients (1.6% vs. 0.9%, P < 0.01; 3.9% vs. 0.8%, P < 0.01). The areas under the ROC curves to predict postoperative AKI by CVP on ICU admission (> 11 mmHg) + LCOS + 24 h PFO (> 5%) and to predict AKI-RRT by CVP on ICU admission (> 13 mmHg) + LCOS + 24 h PFO (> 5%) were 0.763 and 0.886, respectively. CONCLUSION: The volume-associated hemodynamic variables, including CVP on ICU admission, LCOS, and 24 h PFO after surgery could predict postoperative AKI and AKI-RRT.

Takotsubo Cardiomyopathy after Elective Aortic and Mitral Valve Replacement.

Takotsubo cardiomyopathy is a syndrome characterized by transient acute left ventricular dysfunction, electrocardiographic changes that can mimic acute myocardial infarction and minimal release of myocardial enzymes in the absence of obstructive coronary artery disease (CAD). Reports of Takotsubo syndrome after cardiac surgery are exceptional. We describe a case of Takotsubo cardiomyopathy in a 57-year-old man after elective aortic and mitral valve replacement following recent convalescence from infective endocarditis. Takotsubo syndrome should be considered in the differential diagnosis of patients presenting acute myocardial infarction, cardiogenic shock or any low cardiac output syndrome after cardiac surgery.

A sex-balanced rodent model for evaluating phosphine inhalation toxicity.

Exposure to phosphine (PH3 ), a common grain fumigant, is characterized by diverse nonspecific symptoms and a high mortality rate. Although PH3 poisoning is thought to target oxidative respiration, the exact mechanism of action remains largely unknown, resulting in limited treatment options. In our study, the effects of PH3 on female rats were assessed to elucidate potential sex-specific differences and obtain a more comprehensive understanding of PH3 toxicity. Lethality, physiology, and behavior were evaluated in female rats exposed to gaseous PH3 (13,200-26,400 ppm × min), and results were compared with corresponding findings in male rats. Median lethal concentration-time (LCt50 ) and time of death (tTOD ) did not differ significantly between the sexes. Cardiopulmonary changes induced by PH3 were also of comparable magnitude, although temporally, respiratory responses occurred earlier and cardiovascular variations manifested later in female rats. Behavioral observations corroborated physiological findings and indicated a response to hypoxic conditions and low cardiac output. Together, these results provided insights on the toxic mechanisms of PH3 , in particular, its potential interference with oxygen transport and circulation.

Pre-operative neutrophil-lymphocyte ratio predicts low cardiac output in children after cardiac surgery.

Neutrophil-lymphocyte ratio has been associated with clinical outcomes in several groups of cardiac patients, including patients with coronary artery disease, cardiac failure, and cardiac transplant recipients. We hypothesised that pre- and/or post-operative haematological cell counts are associated with clinical outcomes in children undergoing cardiac surgery for CHD. We performed a post hoc analysis of data collected as part of a prospective observational cohort study (n = 83, data available n = 47) of children evaluated for glucocorticoid receptor levels after cardiac surgery (July 2015-January 2016). The association of neutrophil-lymphocyte ratio with low cardiac output syndrome, time to inotrope free, and vasoactive-inotropic score was examined using proportional odds analysis, cox regression, and linear regression models, respectively. A majority (80%) of patients were infants (median/interquartile range 4.1/0.2-7.6 months) with conotruncal (36%) and left-sided obstructed lesions (28%). Two patients required mechanical circulatory support and three died. Higher pre-operative neutrophil-lymphocyte ratio was associated with higher cumulative odds of severe/moderate versus mild low cardiac output on post-operative day 1 (odds ratio 2.86; 95% confidence interval 1.18-6.93; p = 0.02). Pre-operative neutrophil-lymphocyte ratio was not significantly associated with time to inotrope free or vasoactive-inotrope score. Post-operative neutrophil-lymphocyte ratio was also not associated with outcomes. In children after congenital heart surgery, higher pre-operative neutrophil-lymphocyte ratio was associated with a higher chance of low cardiac output in the early post-operative period. Pre-operative neutrophil-lymphocyte ratio maybe a useful prognostic marker in children undergoing congenital heart surgery.

Central hemodynamics are associated with fetal outcomes in pregnancies of advanced maternal age.

OBJECTIVES: Age is a known risk factor for both maternal cardiovascular disease and adverse outcomes in pregnancy. We aimed to characterize the hemodynamic profiles in pregnancies of advanced maternal age (AMA) and correlate these with fetal outcomes. STUDY DESIGN: This was a prospective observational study of pregnancies undergoing antenatal testing. Maternal hemodynamics were measured non-invasively using an imaging probe at the descending aorta and the Uscom BP + arm cuff utilizing pulse pressure wave analysis. The Wilcoxon rank-sum test, Fisher's exact test, and Spearman rank correlation test were used for statistical analysis in R. MAIN OUTCOME MEASURES: Hemodynamic measurements, neonatal birthweight. RESULTS: Twenty-one AMA and twenty-four control patients were enrolled. Mean age ± SD was 39 ± 3.22 in the AMA cohort and 28 ± 4.32 in the control cohort (p < 0.001). AMA patients were evaluated at a later gestational age (36 4/7 weeks) compared to control (34 1/7 weeks, p = 0.02). Between groups, there was no difference in BMI, race, hypertensive disease, diabetes, asthma, drug use, or indication for antenatal testing. 38% (AMA) and 37% (control) had hypertensive disorders of pregnancy. In AMA patients but not control patients, cardiac output (r = 0.52, p = 0.01), systemic vascular resistance (r = -0.53, p = 0.01), and systemic vascular resistance index (r = -0.62, p = 0.002) were significantly correlated with neonatal birthweight percentile. CONCLUSIONS: Hemodynamic alterations consistent with a low output, high resistance cardiovascular circuit were associated with lower birthweight in AMA, but not in control pregnancies.

Validity of transit time-based blood pressure measurements in patients with and without heart failure or pulmonary arterial hypertension across different breathing maneuvers.

PURPOSE: Pulse transit time (PTT) derived by ECG and plethysmographic signal can be a promising alternative to invasive or oscillometry-based blood pressure (BP) monitoring in sleep laboratories because it does not cause arousals from sleep. Therefore, this study assessed the validity of PTT for BP monitoring under sleep laboratory-like conditions. METHODS: Ten volunteers (55.8 ± 19.6 years), 12 patients with heart failure with reduced ejection fraction (HFrEF; 67.3 ± 8.6 years), and 14 patients with Nizza class I pulmonary arterial hypertension (PAH; 59.5 ± 13.4 years) performed different breathing patterns to simulate nocturnal sleep-disordered breathing (SDB). BP was measured at least every 15 min over 1 h using oscillometry (Task Force Monitor™) and PTT (SOMNOscreen™) devices in free breathing conditions and during SDB simulation (alternating phases of hyperventilation and apneas). RESULTS: One hundred forty-two points of measurements were collected. No difference was found in both mean systolic BP (SBP) and diastolic BP (DBP) between oscillometric PTT-based BP measurements in the whole population and throughout the whole recording (SBP 111.3 ± 15.1 mmHg versus 110.0 ± 14.7 mmHg, p = 0.051; DBP 69.9 ± 12.2 versus 69.9 ± 14.2 mmHg, p = 0.701). Likewise, no significant difference in SBP and DBP was found between the two methods in the subgroups of healthy subjects, HFrEF patients and PAH patients, both in free breathing conditions (p > 0.05) and during SDB simulation (p > 0.05). CONCLUSIONS: When monitoring BP in healthy subjects, and in patients with HFrEF or PAH, PTT provides a BP estimation comparable with oscillometric measurement, though slightly inaccurate, both in the condition of regular and unstable breathing.

The effect of milrinone on hemodynamic and gas exchange parameters in children.

Milrinone is a drug frequently used for hemodynamic support in children during critical illness. Although the hemodynamic changes induced by milrinone in children may appear similar to those of adults, the physiologic contributors of these changes remain vastly unknown. A systematic review was conducted to identify studies characterising the hemodynamic effects of milrinone in children during critical illness for hemodynamic support for various medical conditions. Studies were assessed for quality and those of satisfactory quality with pre- and post-operative hemodynamics for each patient were included in the final analyses. Those not limited to children and those not limited to patients with critical illness were excluded from the final analyses. A total of six studies with 791 patients were included in the final analyses. Milrinone infusion doses ranged from 0.3 to 0.75 mcg/kg/minute with the mean infusion dose being 0.5 mcg/kg/minute. Patients whom received milrinone infusion had greater cardiac output, greater left ventricle shortening fraction, lower right ventricular systolic pressure, and lower serum lactate levels. Systolic blood pressure mean arterial blood pressure and arterial oxygen concentration did not significantly change with administration of milrinone. These results were irrespective of milrinone infusion dose, infusion duration, and study size. Milrinone was found to have several beneficial hemodynamic effects in children during critical illness when used at usual clinical doses.

Levosimendan Reduces Mortality and Low Cardiac Output Syndrome in Cardiac Surgery.

BACKGROUND: There has been conflicting evidence concerning the effect of levosimendan on clinical outcomes in patients undergoing cardiac surgery. Therefore, we performed a systematic review and conducted this meta-analysis to provide evidence for/against the administration of levosimendan in cardiac surgery patients. METHODS: We performed a meta-analysis from literature search in PubMed, EMBASE, and Cochrane Library. Only randomized controlled trials comparing the administration of levosimendan in cardiac surgery patients with a control group (other inotrope, standard therapy/placebo, or an intra-aortic balloon pump) were included. In addition, at least one clinical outcome had to be mentioned: mortality, myocardial infarction, low cardiac output syndrome (LCOS), acute kidney injury, renal replacement therapy, atrial fibrillation, prolonged inotropic support, length of intensive care unit, and hospital stay. The pooled treatment effects (odds ratio [OR], 95% confidence intervals [CI]) were assessed using a fixed or random effects model. RESULTS: The literature search retrieved 27 randomized, controlled trials involving a total of 3,198 patients. Levosimendan led to a significant reduction in mortality (OR: 0.67; 95% CI: 0.49-0.91; p = 0.0087). Furthermore, the incidence of LCOS (OR: 0.56, 95% CI: 0.42-0.75; p < 0.0001), acute kidney injury (OR: 0.63; 95% CI: 0.46-0.86; p = 0.0039), and renal replacement therapy (OR: 0.70; 95% CI: 0.50-0.98; p = 0.0332) was significantly decreased in the levosimendan group. CONCLUSION: Our meta-analysis suggests beneficial effects for the prophylactic use of levosimendan in patients with severely impaired left ventricular function undergoing cardiac surgery. The administration of levosimendan was associated with a reduced mortality, less LCOS, and restored adequate organ perfusion reflected in less acute kidney injury.

Preservation of renal function in cardiac surgery patients with low cardiac output syndrome: levosimendan vs beta agonists.

BACKGROUND: Some studies have been performed to assess the effects of levosimendan on cardiac function when administered to cardiac surgery patients with low cardiac output syndrome (LCOS) in the immediate postoperative period. Levosimendan is an inotropic agent for the treatment of low cardiac output syndrome that seems to have a protective effect on renal function. METHODS: It is a quasi-experimental study. A total of 100 patients with LCOS received either beta-agonists or levosimendan. We assessed the incidence of postoperative kidney failure in cardiac surgery patients. In patients who had kidney failure at diagnosis of LCOS, we examined whether differences existed in the evolution of kidney failure based on the treatment administered for LCOS. The parameters measured included haemodynamics, oxygen supply, and renal function as assessed by the AKI scale. ANOVA, Student's t-test and Wilcoxon or Friedman tests were used. RESULTS: Up to 30% of cardiac surgery patients had kidney failure at diagnosis of LCOS. Kidney failure at discharge from the ICU was more frequent in patients who received beta-agonist drugs as compared to those who received levosimendan (p < 0.05). CONCLUSION: The incidence of kidney failure decreased with the postoperative administration of levosimendan to cardiac surgery patients with LCOS, as compared to beta-agonists. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 46058317. Date of registration: 7/10/2019. Retrospectively registered.

Ultimate Third Heart Sound.

A 79-year-old man with dilated cardiomyopathy and severe functional mitral regurgitation presented with general fatigue and dyspnea. Auscultation revealed a systolic regurgitant murmur with a minimized second heart sound due to a low output. On the other hand, the third heart sound was ultimately enhanced, being visible and palpable as a pulsatile knock of the precordium. Phonocardiography and echocardiography successfully confirmed early-diastolic rapid distension of the left ventricle along with rapid ventricular filling and abrupt deceleration of the atrioventricular blood flow to be the precise etiology of the ultimate third heart sound, indicating critically deteriorated hemodynamics due to massive mitral regurgitation combined with a low output.

Postoperative cerebral oxygenation was not associated with new brain injury in infants with congenital heart disease.

OBJECTIVE: The aim of this study was to evaluate postoperative indices of cerebral oxygenation and autoregulation in infants with critical congenital heart disease in relation to new postoperative ischemic brain injury. METHODS: This prospective, clinical cohort included 77 infants with transposition of the great arteries (N = 19), left ventricular outflow tract obstruction (N = 30), and single ventricle physiology (N = 28) undergoing surgery at 30 days or less of life. Postoperative near-infrared spectroscopy and physiologic monitoring were applied to extract mean arterial blood pressure, regional cerebral oxygen saturation, fractional tissue oxygen extraction, and regional cerebral oxygen saturation mean arterial blood pressure correlation coefficient (≥0.5 considered sign of impaired cerebral autoregulation). New postoperative ischemic injury was defined as moderate-severe white matter injury or focal infarction on magnetic resonance imaging. Low cardiac output syndrome was measured as lactate greater than 4 mmol/L with pH less than 7.30. RESULTS: After surgery, regional cerebral oxygen saturation was decreased in all congenital heart disease groups with a notable increase in regional cerebral oxygen saturation between 6 and 12 hours after surgery, on average with a factor of 1.4 (range, 1.1-2.4). Both single ventricle physiology and postoperative low cardiac output syndrome were associated with lower regional cerebral oxygen saturation and increased time with correlation coefficient of 0.5 or greater. New postoperative ischemic injury was seen in 39 patients (53%) and equally distributed across congenital heart disease groups. Postoperative regional cerebral oxygen saturation, fractional tissue oxygen extraction, and correlation coefficient were not independently associated with new postoperative white matter injury or focal infarction (mixed-model analysis, all F > 0.12). CONCLUSIONS: Postoperative indices of cerebral oxygenation and cerebral autoregulation are not independent predictors of new ischemic brain injury in infants with critical congenital heart disease. Further exploration of the complex interplay among low regional cerebral oxygen saturation, low cardiac output syndrome, and heart defect is required to identify potential biomarkers enabling early intervention for ischemic brain injury.