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.

Protected cardiac surgery: strategic mechanical circulatory support to improve postcardiotomy mortality.

PURPOSE OF REVIEW: To examine the evolving landscape of cardiac surgery, focusing on the increasing complexity of patients and the role of mechanical circulatory support (MCS) in managing perioperative low cardiac output syndrome (P-LCOS). RECENT FINDINGS: P-LCOS is a significant predictor of mortality in cardiac surgery patients. Preoperative risk factors, such as cardiogenic shock and elevated lactate levels, can help identify those at higher risk. Proactive use of MCS, rather than reactive implementation after P-LCOS develops, may lead to improved outcomes by preventing severe organ hypoperfusion. The emerging concept of "protected cardiac surgery" emphasizes early identification of these high-risk patients and planned MCS utilization. Additionally, specific MCS strategies are being developed and refined for various cardiac conditions, including AMI-CS, valvular surgeries, and pulmonary thromboendarterectomy. SUMMARY: This paper explores the shifting demographics and complexities in cardiac surgery patients. It emphasizes the importance of proactive, multidisciplinary approaches to identify high-risk patients and implement early MCS to prevent P-LCOS and improve outcomes. The concept of protected cardiac surgery, involving planned MCS use and shared decision-making, is highlighted. The paper also discusses MCS strategies tailored to specific cardiac procedures and the ethical considerations surrounding MCS implementation.

Early postoperative beta-blockers are associated with improved cardiac output after late complete repair of tetralogy of Fallot: a retrospective cohort study.

Tetralogy of Fallot is the most common cyanotic congenital heart disease. For decades, our institution has cared for humanitarian patients with late presentation of tetralogy of Fallot. They are characterized by severe right ventricular hypertrophy with consecutive diastolic dysfunction, increasing the risk of postoperative low cardiac output syndrome (LCOS). By right ventricular restrictive physiology, we hypothesized that patients receiving early postoperative beta-blockers (within 48 h after cardiopulmonary bypass) may have better diastolic function and cardiac output. This is a retrospective cohort study in a single-center tertiary pediatric intensive care unit. We included > 1-year-old humanitarian patients with a confirmed diagnosis of tetralogy of Fallot undergoing a complete surgical repair between 2005 and 2019. We measured demographic data, preoperative echocardiographic and cardiac catheterization measures, postoperative mean heart rate, vasoactive-inotropic scores, LCOS scores, length of stay, and mechanical ventilation duration. One hundred sixty-five patients met the inclusion criteria. Fifty-nine patients (36%) received early postoperative beta-blockers, associated with a lower mean heart rate, higher vasoactive-inotropic scores, and lower LCOS scores during the first 48 h following cardiopulmonary bypass. There was no significant difference in lengths of stay and ventilation. Conclusion: Early postoperative beta-blockers lower the prevalence of postoperative LCOS at the expense of a higher need for vasoactive drugs without any consequence on length of stay and ventilation duration. This approach may benefit the specific population of children undergoing a late complete repair of tetralogy of Fallot. What is Known: • Prevalence of low cardiac output syndrome is high following a late complete surgical repair of tetralogy of Fallot. What is New: • Early postoperative beta-blockade is associated with lower heart rate, prolonged relaxation time, and lower prevalence of low cardiac output syndrome. • Negative chronotropic agents like beta-blockers may benefit selected patients undergoing a late complete repair of tetralogy of Fallot, who are numerous in low-income countries.

Preoperative Levosimendan in Patients With Severe Left Ventricular Dysfunction Undergoing Isolated Coronary Artery Bypass Grafting: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To verify the impact of preoperative levosimendan on patients with severe left ventricular dysfunction (ejection fraction <35%) undergoing isolated coronary artery bypass grafting. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: The authors included 1,225 patients from 6 randomized controlled trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors performed a meta-analysis of trials that compared preoperative levosimendan with placebo or no therapy, reporting efficacy and safety endpoints. Statistical analyses used mean differences and risk ratios (RR), with a random effects model. Six studies were included, comprising 1,225 patients, of whom 615 (50.2%) received preoperative levosimendan, and 610 (49.8%) received placebo/no therapy. Preoperative levosimendan showed a lower risk of all-cause mortality (RR 0.31; 95% CI 0.16-0.60; p < 0.01; I2 = 0%), postoperative acute kidney injury (RR 0.44; 95% CI 0.25-0.77; p < 0.01; I2 = 0%), low-cardiac-output syndrome (RR 0.45; 95% CI 0.30-0.66; p < 0.001; I2 = 0%), and postoperative atrial fibrillation (RR 0.49; 95% CI 0.25-0.98; p = 0.04; I2 = 85%) compared to control. Moreover, levosimendan significantly reduced the need for postoperative inotropes and increased the cardiac index at 24 hours postoperatively. There were no differences between groups for perioperative myocardial infarction, hypotension, or any adverse events. CONCLUSION: Preoperative levosimendan in patients with severe left ventricular dysfunction undergoing isolated coronary artery bypass grafting was associated with reduced all-cause mortality, low-cardiac-output syndrome, acute kidney injury, postoperative atrial fibrillation, and the need for circulatory support without compromising safety.

Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial.

BACKGROUND: Cardiac surgery involving cardiopulmonary bypass induces a significant systemic inflammatory response, contributing to various postoperative complications, including pulmonary dysfunction, myocardial and kidney injuries. OBJECTIVE: To investigate the effect of Nitric Oxide delivery via the cardiopulmonary bypass circuit on various postoperative outcomes. DESIGN: A prospective, single-centre, double-blinded, randomised controlled trial. SETTING: Rabin Medical Centre, Beilinson Hospital, Israel. PATIENTS: Adult patients scheduled for elective cardiac surgery were randomly allocated to one of the study groups. INTERVENTIONS: For the treatment group, 40 ppm of nitric oxide was delivered via the cardiopulmonary bypass circuit. For the control group, nitric oxide was not delivered. OUTCOME MEASURES: The primary outcome was the incidence of hypoxaemia, defined as a p a O2 /FiO 2 ratio less than 300 within 24 h postoperatively. The secondary outcomes were the incidences of low cardiac output syndrome and acute kidney injury within 72 h postoperatively. RESULTS: Ninety-eight patients were included in the final analysis, with 47 patients allocated to the control group and 51 to the Nitric Oxide group. The Nitric Oxide group exhibited significantly lower hypoxaemia rates at admission to the cardiothoracic intensive care unit (47.1 vs. 68.1%), P  = 0.043. This effect, however, varied in patients with or without baseline hypoxaemia. Patients with baseline hypoxaemia who received nitric oxide exhibited significantly lower hypoxaemia rates (61.1 vs. 93.8%), P  = 0.042, and higher p a O2 /FiO 2 ratios at all time points, F (1,30) = 6.08, P  = 0.019. Conversely, this benefit was not observed in patients without baseline hypoxaemia. No significant differences were observed in the incidence of low cardiac output syndrome or acute kidney injury. No substantial safety concerns were noted, and toxic methaemoglobin levels were not observed. CONCLUSIONS: Patients with baseline hypoxaemia undergoing cardiac surgery and receiving nitric oxide exhibited lower hypoxaemia rates and higher p a O2 /FiO 2 ratios. No significant differences were found regarding postoperative pulmonary complications and overall outcomes. TRIAL REGISTRATION: NCT04807413.

The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction.

BACKGROUND: The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. OBJECTIVE: This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. STUDY DESIGN: This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. RESULTS: A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotropy index (rs=0.162), whereas there was a negative correlation with maternal systemic vascular resistance (rs=-0.264) and maternal potential energy-to-kinetic energy ratio (rs=-0.171). The fetal umbilical vein flow and the flow corrected for estimated fetal weight were positively correlated with maternal cardiac output (rs=0.339 and rs=0.297) and maternal inotropy index (rs=0.217 and r=0.336), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.461 and rs=-0.409) and maternal potential energy-to-kinetic energy ratio (rs=-0.336 and rs=-0.408). CONCLUSION: Maternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Extending the 'host response' paradigm from sepsis to cardiogenic shock: evidence, limitations and opportunities.

Recent clinical and research efforts in cardiogenic shock (CS) have largely focussed on the restoration of the low cardiac output state that is the conditio sine qua non of the clinical syndrome. This approach has failed to translate into improved outcomes, and mortality has remained static at 30-50%. There is an unmet need to better delineate the pathobiology of CS to understand the observed heterogeneity of presentation and treatment effect and to identify novel therapeutic targets. Despite data in other critical illness syndromes, specifically sepsis, the role of dysregulated inflammation and immunity is hitherto poorly described in CS. High-dimensional molecular profiling, particularly through leukocyte transcriptomics, may afford opportunity to better characterise subgroups of patients with shared mechanisms of immune dysregulation. In this state-of-the-art review, we outline the rationale for considering molecular subtypes of CS. We describe how high-dimensional molecular technologies can be used to identify these subtypes, and whether they share biological features with sepsis and other critical illness states. Finally, we propose how the identification of molecular subtypes of patients may enrich future clinical trial design and identification of novel therapies for CS.

Evaluation of levosimendan as treatment option in a large case-series of preterm infants with cardiac dysfunction and pulmonary hypertension.

Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. The design/setting of the evaluation is in a large case-series of preterm infants with CD and PH. Data of all preterm infants (gestational age (GA) < 37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. The primary clinical endpoint was defined as echocardiographic response to levosimendan. Preterm infants (105) were finally enrolled for further analysis. The preterm infants (48%) were classified as extremely low GA newborns (ELGANs, < 28 weeks of GA) and 73% as very low birth weight infants (< 1500 g, VLBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24 h) in about 30%, with a significant decrease in the responder group (p < 0.001). The incidence of left ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24 h) in the responder-group (p = 0.007, and p < 0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12 h (3.6 mmol/l, p < 0.05), and 24 h (3.1 mmol/l, p < 0.01).  Conclusion: Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the mean arterial pressure during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted. What is Known: • Levosimendan as a calcium-sensitizer and inodilator is known to improve the low cardiac output syndrome (LCOS), and improves ventricular dysfunction, and PH, both in pediatric as well as in adult populations. Data related to critically ill neonates without major cardiac surgery and preterm infants are not available. What is New: • This study evaluated the effect of levosimendan on hemodynamics, clinical scores, echocardiographic severity parameters, and arterial lactate levels in a case-series of 105 preterm infants for the first time. Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as surrogate marker for a LCOS. • How this study might affect research, practice, or policy. As no data are available regarding the use of levosimendan in this population, our results hopefully animate the research community to conduct future prospective trails analyzing levosimendan in randomized controlled trials (RCT) and observational control studies. Additionally, our results potentially motivate clinicians to introduce levosimendan as second second-line therapy in cases of severe CD and PH in preterm infants without improvement using standard treatment strategies.

Development and Validation of a Prediction Score for Low-Cardiac-Output Syndrome After Adult Cardiac Surgery.

OBJECTIVES: The authors aimed to develop a simple prediction score to help identify patients at high risk of low-cardiac-output syndrome after adult cardiac surgery. DESIGN: A single-center, retrospective, observational study. SETTING: At a tertiary hospital. PARTICIPANTS: Adult patients who underwent on-pump cardiac surgery between April 2016 and March 2021. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among the 2,806 patients retained for final analyses, 355 (12.7%) developed low-cardiac-output syndrome. Using a stepwise backward variable selection procedure applied to a multivariate logistic regression, a prediction model, including 8 risk factors, could be identified-preoperative left ventricular ejection fraction, glomerular filtration rate <60 mL/min according to the Cockcroft formula or preoperative dialysis, combined surgery, nonelective surgery, mitral valve surgery for mitral valve regurgitation, history of extracardiac arteriopathy, preoperative hemoglobin <13 g/dL, and New York Heart Association functional class III or IV. A clinical prediction score was derived from the regression coefficients. The model had a good discriminative ability, with an area under the receiver operating characteristics curve of 0.8 (95% CI: 077-0.84). Using a threshold value of 5, the score had a 68% sensitivity, 79% specificity, a positive-predictive value of 33%, and a negative-predictive value of 94%. These results were validated on a validation sample using the bootstrap resampling technique. CONCLUSIONS: The authors developed a clinical score to facilitate the prediction of low- cardiac-output syndrome after adult cardiac surgery. This could help tailor patient management by contributing to the early identification of those at high risk of postoperative low cardiac output.

Effects of Low-Dose Tadalafil in a Patient with Biventricular Heart Failure: A Case Report.

Phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil, can improve cardiac output by increasing left ventricular preload; however, there are concerns that this can increase the risk of heart failure due to pulmonary congestion in patients with elevated left ventricular end-diastolic pressure. We encountered a case in which low dose tadalafil improved the hemodynamics of a 66-year-old male patient with dilated cardiomyopathy (DCM) with congestion and low cardiac output due to biventricular dysfunction. The patient received a cardiac resynchronization therapy defibrillator (CRT-D) and appropriate medical therapy for heart failure. During a hemodynamic evaluation after heart failure symptoms were alleviated, we attempted to increase the dose of renin-angiotensin-aldosterone system (RAAS) inhibitors, which contribute to low cardiac output, hypotension, and worsening of renal function. However, the administration of a low dose of tadalafil for the patient's benign prostatic hyperplasia allowed for the increase in the dose of RAAS inhibitors and markedly improved his subjective symptoms and hemodynamics. Because of the biventricular dysfunction in severe cases, we often experience further promotion of low cardiac output by standard treatments such as RAAS inhibitors, in which low doses of PDE5 inhibitors may be effective in maintaining biventricular linkage. PDE5 inhibitors may be effective in patients, who are not able to increase the dose of RAAS inhibitors due to low cardiac output.

Evaluation of perfusion index and left ventricular output changes in low cardiac output syndrome after arterial switch operation.

INTRODUCTION: Transposition of great arteries is one of newborns' most common cyanotic CHDs, and its treatment is arterial switch operation in the first days of life. Low cardiac output syndrome may develop in the early postoperative period. In this study, we evaluated perfusion index and left ventricular output blood flow changes in patients who underwent arterial switch operation and developed low cardiac output syndrome. METHODS: This study was conducted prospectively in newborns with transposition of great arteries who underwent arterial switch operation between 1st August 2020 and 1st August 2022. Low cardiac output syndrome score and left ventricular output were investigated. Initially, 6th, 12th, 18th, and 24th hour perfusion index and left ventricular output values of patients with and without low cardiac output syndrome were recorded. The results were evaluated statistically. RESULTS: A total of 60 patients were included in the study. Sex distribution was equal. The median age at the time of surgery was 5 days (interquartile range 3-7 days), and the median weight was 3.1 kg (interquartile range 2.9-3. 4). Low cardiac output syndrome was detected in 30% (n = 18) of cases. The median perfusion index of patients who developed low cardiac output syndrome was significantly lower at the 12th, 18th, and 24th hours (p < 0.05) (0.99 versus 1.25, 0.86 versus 1.21, and 0.96 versus 1.33, respectively). Similarly, the median left ventricular output of patients who developed low cardiac output syndrome was significantly lower at 12th, 18th, and 24th hours (p < 0.05) (95 versus 110 ml/kg/min, 89 versus 109 ml/kg/min, and 92 versus 112 ml/kg/min, respectively). There was a significant correlation between perfusion index values and left ventricular output at all measurements (r > 0.500, p < 0.05). CONCLUSION: Perfusion index and left ventricular output measurements decreased in newborns who developed low cardiac output syndrome after arterial switch operation, especially at 12th and 18th hours. Serial perfusion index and left ventricular output measurements can be instructive in predicting low cardiac output syndrome development.

[Intensive Care in Heart Surgery - is All Now Different?] / Intensivtherapie in der Herzchirurgie ­ alles anders?

With approximately 100000 operations performed in Germany per year, cardiac surgery is among the surgical specialties that require intensive care tratment most frequently. Although all therapeutic aspects of ICU treatment are of high importance among cardiac surgery patients, there is a focus on hemodynamics with the overarching goal of sufficient oxygen delivery. Patients undergoing cardiac surgery are particularily prone to hemodynamic instability and low cardiac output syndrome, potentially culminating into cardiogenic shock. This article presents an overview of essential elements of intensive care medicine in cardiac surgery, paying special attention to hemodynamic monitoring, low cardiac output syndrome, inotropy, cardiac arrhyhmia, perioperative myocardial infarction, and patient blood management.

[Low Output Syndrome:Points to Consider for Intraoperative Myocardial Protection and Treatment Methods].

Low cardiac output syndrome (LOS) is a condition that causes low perfusion and perfusion failure of the entire body's tissues due to a decline in heart contractile strength, posing a significant challenge in cardiothoracic surgical perioperative management. Appropriate myocardial protection is crucial to prevent ischemia-reperfusion injury during open-heart surgery and prevent LOS. The integrated myocardial protection method, proposed by Buckberg et al., is one technique employed for this purpose. In the treatment of LOS, interventions are made in the parameters of stroke volume and heart rate, structural abnormalities are excluded and dealt with, and mechanical assistance is utilized when necessary. With the aging and increasing severity of surgical patients, the risk of postoperative LOS is on the rise. Therefore, the application of appropriate myocardial protection and treatment methods leads to improved prognosis. It's worth noting that ensuring optimal myocardial protection during surgery and the correct application of medication and devices for intervention can significantly improve patient outcomes. With the rise in high-risk surgical cases due to aging and an increase in severe conditions, the importance of these interventions cannot be overstated.

Frequency of Low Cardiac Output Syndrome Following on Pump Coronary Artery Bypass Grafting Surgery and it's Association with Degree of Pre-operative Left Ventricular Dysfunction.

Background Low cardiac output syndrome (LCOS) is a serious complication after coronary artery bypass grafting (CABG) surgery. It is associated with 10 times to 17 times increase in mortality and markedly increase morbidity. Objective To find out the frequency of Low cardiac output syndrome following on pump coronary artery bypass grafting surgery, to determine the association of Low cardiac output syndrome with degree of pre-operative left ventricular dysfunction and to compare in hospital outcomes of coronary bypass surgery with and without low cardiac output syndrome. Method This prospective, descriptive study enrolled 200 patients who underwent on pump coronary artery bypass grafting surgery using antegrade St Thomas blood cardioplegia. Pre-operatively grouped into two groups consisting Group A of 100 patients with pre-operative left ventricular ejection fraction (LVEF) ≥ 40% and group B of 100 patients with pre-operative left ventricular ejection fraction (LVEF) < 40%. Post-operatively frequency of low cardiac output syndrome was compared between the groups and in-hospital outcomes were studied. Result The mean age of the patients in the study was 53.50±7.57 years. Male to female ratio was 1.8:1. Results showed overall frequency of low cardiac output syndrome was 21.5%. The frequency of LCOS was 15 vs 28% (p - 0.038) in patients with preoperative LV EF ≥ 40% and < 40% respectively. The outcomes of coronary artery bypass grafting surgery were stroke (3.82 vs. 30.23%, p - 0.001), acute kidney injury (5.09 vs. 23.25%, p - 0.001), respiratory failure (6.36 vs. 34.88%, p - 0.001), ICU stay days (4.75 ± 1.28 vs. 7.44 ± 4.66, p - 0.018), hospital stay days (9.56 ± 2.40 vs. 15.22 ± 3.89, p - 0.001) and mortality (4.45 vs. 32.55%, p - 0.001) in patients without and with low cardiac output syndrome respectively. Conclusion The frequency of low cardiac output syndrome following coronary artery bypass surgery is 21.5%. Left ventricular dysfunction pre-operatively is associated with high frequency of low cardiac output syndrome following surgery. There is significantly poor outcome of coronary artery bypass surgery with low cardiac output syndrome in terms of stroke, respiratory failure, acute kidney injury, mortality and significant ICU stay, hospital stay in compare to patients without low cardiac output syndrome.

Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure.

BACKGROUND: Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. METHODS: We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema. RESULTS: Of the 881 patients who underwent randomization, 440 were assigned to receive sacubitril-valsartan and 441 to receive enalapril. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change, -46.7% vs. -25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001). The greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. CONCLUSIONS: Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. (Funded by Novartis; PIONEER-HF ClinicalTrials.gov number, NCT02554890 .).

Procedure-Specific Relationships Between Postoperative Troponin T and a Composite of Mortality and Low Cardiac Output Syndrome: A Retrospective Cohort Analysis.

BACKGROUND: Myocardial injury after coronary artery bypass grafting (CABG) is defined as troponin concentrations >10 times 99th percentile upper reference limit (URL) according to the Fourth Universal Definition. However, troponin concentrations after non-CABG cardiac surgery which indicate greater-than-expected myocardial injury and increased risk for complications remain unclear. Our goal was to assess procedure-specific relationships between troponin T and a composite outcome of low cardiac output syndrome and in-hospital mortality in cardiac surgical patients. METHODS: Patients having cardiac surgery between January 2010 and December 2017 were categorized into 4 groups by procedure: (1) CABG; (2) mitral valve repair; (3) aortic valve repair/replacement (AVR); (4) mitral valve replacement (MVR) or CABG + valve surgeries. Exclusion criteria were elevated preoperative troponin T, preoperative kidney failure, circulatory arrest, or preoperative/planned mechanical circulatory support. Logistic regression was used to assess the association between troponin T and composite outcome, both overall and by procedure, including assessment of the interaction between procedure and troponin T on outcome. RESULTS: Among 10,253 patients, 37 (0.4%) died and 393 (3.8%) developed the primary outcome. Troponin T concentrations differed by procedure (P < .001). Compared to CABG, AVR had 0.53 (99.2% confidence interval [CI], 0.50-0.56; unadjusted P < .001) times lower troponin T concentrations, while MVR/CABG + valve were 1.54 (99.2% CI, 1.45-1.62, unadjusted P < .001) times higher. There were linear relationships between log2 troponin T concentration and log odds mortality/low cardiac output syndrome. The (unadjusted) relationships were parallel for various types of surgery (interaction P = .59), but at different levels of the outcome. CONCLUSIONS: The relative increase in odds for mortality/low cardiac output syndrome per a similar increase in troponin T concentrations did not differ among cardiac surgical procedures, but the absolute troponin T concentrations did. Troponin concentrations should thus be interpreted in context of surgical procedure.

Effect of Levosimendan Treatment in Pediatric Patients With Cardiac Dysfunction: An Update of a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Levosimendan increasingly has been used to treat heart failure and cardiac dysfunction in pediatric patients. Currently, there is only limited evidence that this drug positively affects outcomes. The authors' aim was to investigate the effects of levosimendan on hemodynamic parameters and outcomes in pediatric patients in all clinical settings. The study design was a systematic review of randomized and nonrandomized studies. Randomized clinical trials (RCTs) were included in a meta-analysis. The primary outcome of the meta-analysis was the effect of levosimendan on central venous oxygen saturation (ScvO2) and lactate values as surrogate markers of low-cardiac-output syndrome. The study setting was any acute care setting. Study participants were pediatric patients (age <18 years) receiving levosimendan, and the intervention was levosimendan versus any control treatment. The authors identified 44 studies published from 2004 to 2020, including a total of 1,131 pediatric patients. Nine studies (enrolling 547 patients) were RCTs, all performed in a pediatric cardiac surgery setting. Three RCTs were judged to carry a low risk of bias. In the RCTs, levosimendan administration was associated with a significant improvement of ScvO2 (p = 0.03) and a trend toward lower postoperative lactate levels (p = 0.08). No differences could be found for secondary outcomes. Levosimendan use in pediatric patients is not associated with major side effects and may lead to hemodynamic improvement after cardiac surgery. However, its impact on major clinical outcomes remains to be determined. Overall, the quality of evidence for levosimendan use in pediatric patients is low, and further high-quality RCTs are needed.

Indonesian Study: Triiodothyronine for Infants Less than 5 Months Undergoing Cardiopulmonary Bypass.

This study evaluates the efficacy and safety of oral triiodothyronine on time to extubation for infants less than 5 months undergoing heart surgery in Indonesia, and primarily relates to patients in emerging programs with high malnutrition and mortality. In this randomized, double-blind, placebo-controlled trial, oral triiodothyronine (T3, Tetronine®) 1 µg/kg-body weight/dose or placebo (saccharum lactis) was administered via nasogastric tube every 6 h for 60 h to treatment group. A total of 120 patients were randomized into T3 (61 patients) and placebo (59 patients) groups. The majority of the patients had moderate to severe malnutrition (55.83%) with a high post-operative mortality rate of 23.3%. The T3 group showed significantly higher serum FT3 levels from 1 until 48 h post cross-clamp removal (p < 0.0001), lower incidence of low cardiac output syndrome at both 6 h (28 [45.9%] vs. 39 [66.1%] patients, p = 0.03, OR 2.3, 95% CI: 1.10-4.81) and 12 h after cross-clamp removal (25 [41.7%] vs. 36 [63.2%], p = 0.02, OR 2.40, 95% CI: 1.14-5.05). Although not statistically significant, the treatment group had shorter median (IQR) intubation time (2.59 [1.25-5.24] vs. 3.77 [1.28-6.64] days, p = 0.16, HR 1.36, 95% CI: 0.88-2.09)] and lower mortality (10 [16.4%] vs. 18 [30.5%], p = 0.07]. Patients with Aristotle score < 10.0 (low risk) receiving T3 had faster extubation than placebo patients (p = 0.021, HR of 1.90, 95% CI: 1.10-3.28) and were significantly less likely to require CPR or experience infection (p = 0.027, OR 8.56, 95% CI:0.99-73.9 and p = 0.022, OR 4.09 95% CI: 1.16-14.4, respectively). Oral T3 supplementation reduced overall incidence of low cardiac output syndrome and significantly reduced the time to extubation in low-risk patients. Therefore, prophylactic oral T3 administration may be beneficial in these patients.Trial Registration: ClinicalTrials.gov NCT02222532.

A Path FORWARD: Development of a Comprehensive Multidisciplinary Clinic to Create Health and Wellness for the Child and Adolescent with a Fontan Circulation.

Today, it is anticipated most individuals diagnosed with single-ventricle malformation will survive surgical reconstruction through a successful Fontan operation. As greater numbers of patients survive, so has the recognition that individuals with Fontan circulation face a variety of challenges. The goal of a normal quality and duration of life will not be reached by all. The hurdles fall into a variety of domains. From a cardiovascular perspective, the Fontan circulation is fundamentally flawed by its inherent nature of creating a state of chronically elevated venous pressure and congestion, accompanied by a relatively low cardiac output. Ventricular dysfunction, atrioventricular valve regurgitation, and arrhythmia may directly impact cardiac performance and can progress with time. Problems are not limited to the cardiovascular system. Fontan circulatory physiology impacts a multitude of biological processes and health parameters outside the heart. The lymphatic circulation is under strain manifesting as variable degrees of protein-rich lymph loss and immune system dysregulation. Organ system dysfunction develops through altered perfusion profiles. Liver fibrosis is ubiquitous, and a process of systemic fibrogenesis in response to circulatory stressors may affect other organs as well. Somatic growth and development can be delayed. Behavioral and mental health problems are common, presenting as clinically important levels of anxiety and depression. Most striking is the high variability in prevalence and magnitude of these complications within the population, indicating the likelihood of additional factors enhancing or mitigating their emergence. We propose that optimal care for the individual with single ventricle and a Fontan circulation is ideally offered in a comprehensive multidisciplinary manner, with attention to elements that are beyond cardiac management alone. In this report, we share the concepts, our experiences, and perspectives on development of a clinic model-the "Fontan rehabilitation, wellness and resilience development" or FORWARD program. We provide insights into the mechanics of our multidisciplinary model of care and the benefits offered serving our growing population of individuals with a Fontan circulation and their families.

Comprehensive and Safe Decongestion in Acutely Decompensated Heart Failure.

PURPOSE OF THE REVIEW: Progressive intravascular, interstitial, and alveolar fluid overload underlies the transition from compensated to acutely decompensated heart failure and loop diuretics are the mainstay of treatment. Adverse effects and resistance to loop diuretics received much attention while the contribution of a depressed cardiac output to diuretic resistance was downplayed. RECENT FINDINGS: Analysis of experience with positive inotropic agents, especially dobutamine, indicates that enhancement of cardiac output is not consistently associated with increased renal blood flow. However, urinary output and renal sodium excretion increase likely due to dobutamine-mediated decrease in renal and systemic reduced activation of sympathetic nervous- and renin-angiotensin-aldosterone system. Mechanical circulatory support with left ventricular assist devices ascertained the contribution of low cardiac output to diuretic resistance and the pathogenesis and progression of kidney disease in acutely decompensated heart failure. Diuretic resistance commonly occurs in acutely decompensated heart failure. However, failure to resolve fluid overload despite high doses of loop diuretics should alert to the presence of a low cardiac output state.