Low Cardiac Output Research Articles

Empowering Little Fighters: Post-Cardiotomy Pediatric ECMO and the Journey to Recovery.

Extra Corporeal Membrane Oxygenation (ECMO) has long been used for cardiorespiratory support in the immediate post-paediatric cardiac surgery period with a 2-3% success as per the ELSO registry. Success in recovery depends upon the optimal delivery of critical care to paediatric patients and a comprehensive healthcare team. The survival benefit of children placed on central veno arterial (VA) ECMO following elective cardiac surgeries for congenital heart disease (n = 672) was studied in a cohort of 29 (4.3%) cases from the period of Jan 2018 to Dec 2022 in our cardiac surgical centre. Indications for placing these patients on central VA ECMO included inability to wean from cardiopulmonary bypass (CPB), low cardiac output syndrome, severe pulmonary arterial hypertension, significant bleeding, anaphylaxis, respiratory failure and severe pulmonary edema. The mean time to initiation of ECMO was less than 5 h and the mean duration of ECMO support was 56 h with a survival rate of 58.3%. Amongst perioperative complications, sepsis and arrhythmia on ECMO were found to be negatively associated with survival. Improvements in the pH, PaO2 levels and serum lactate levels after initiation of ECMO were associated with survival benefits. The early initiation of ECMO for paediatric cardiotomies could be a beacon of hope for families and medical teams confronting these challenging situations. Improvement in indicators of adequate perfusion and ventricular recoveries like pH and serum lactate and absence of arrhythmia and sepsis are associated with good outcomes.

Association of Vasoactive-Inotropic Score with Postoperative Outcomes in Children with Congenital Heart Diseases Undergoing Cardiac Surgery

Objectives: This cross-sectional study aimed to evaluate the association between the vasoactive-inotropic score (VIS) and post-operative morbidity and mortality in pediatric patients undergoing cardiac surgery for congenital heart diseases (CHDs). Methodology: A cross-sectional study was conducted at the Pediatric Cardiac Intensive Care Unit (PCICU) of the National Institute of Cardiovascular Diseases, Karachi, Pakistan, between October 2021 and March 2022. A total of 101 children up to 18 years of age admitted to the PCICU were included in the analysis. Demographic characteristics and peri-operative variables were recorded, and VIS scores were collected to assess their association with post-surgery outcomes. A score of ≥15 was considered high, while a score <15 was considered low. Results: Among the 101 children included in the study, 49 (48.5%) were male and 52 (51.5%) were female, with a mean age of 7.45±2.81 years. Fifteen (14.9%) patients had a high VIS score during their ICU stay, while 86 patients had a low VIS score. Low cardiac output was the most common post-operative morbidity observed in 9 (8.9%) children, followed by hepatic dysfunction and acute kidney injury, each reported in 8 (7.9%) children. Significant associations were found between high VIS and hepatic dysfunction (p<0.001), acute kidney injury (p<0.001), low cardiac output (p<0.001), neurological dysfunction (p=0.016), and mortality (p<0.001). Conclusion: High VIS scores were significantly associated with poor short-term morbidity and mortality in children undergoing corrective surgery for CHDs. The VIS system can aid in predicting disease progression, severity, and outcomes in pediatric cardiac surgical patients.

Correlation between Post-operative Serum Lactate Levels and Low Cardiac Output Syndrome in Patients Undergoing Coronary Artery Bypass Grafting Surgery: A Prospective Study in a Tertiary Care Hospital

Objectives: This study aimed to assess the correlation between the development of low cardiac output syndrome (LCOS) and post-operative serum lactate levels in patients undergoing coronary artery bypass grafting (CABG) surgery at a tertiary care hospital. Methodology: A prospective cross-sectional study was conducted from January to June 2021, involving 50 patients undergoing CABG surgery with cardiopulmonary bypass. Arterial samples were obtained immediately post-surgery and at six, twelve, and twenty-four-hour intervals post-operatively. The association between lactate levels and the occurrence of LCOS, need for inotropic support, and intra-aortic balloon pump (IABP) utilization was evaluated. Results: The study comprised predominantly male patients (84%). Patients were categorized into two groups based on lactate levels: Group 1 (> 4 mmol/L) and Group 2 (< 4 mmol/L). In Group 1, 32% of patients developed LCOS, 10% required IABP, and 20% needed inotropic and vasopressor support. Immediately post-CABG, the mean lactate level was 7.5 mmol/L, with 3% requiring IABP and 20% needing double inotropic support. Lactate levels decreased over time, with mean levels at six, twelve, and twenty-four hours post-surgery being 6.3 mmol/L, 3.8 mmol/L, and 3.3 mmol/L, respectively. Correspondingly, the need for IABP and inotropic support decreased. LCOS occurrence within 24 hours post-surgery correlated significantly with elevated lactate levels (p < 0.05). Conclusion: Elevated lactate levels were associated with the development of LCOS within 24 hours post-CABG surgery. Monitoring lactate levels postoperatively may serve as a valuable tool in predicting and managing LCOS in CABG patients.

Inhaled nitric oxide and postoperative outcomes in cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis

Cardiac surgeries under cardiopulmonary bypass (CPB) are complex procedures with high incidence of complications, morbidity and mortality. The inhaled nitric oxide (iNO) has been frequently used as an important composite of perioperative management during cardiac surgery under CPB. We conducted a meta-analysis of published randomized clinical trials (RCTs) to assess the effects of iNO on reducing postoperative complications, including the duration of postoperative mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, mortality, hemodynamic improvement (the composite right ventricular failure, low cardiac output syndrome, pulmonary arterial pressure, and vasoactive inotropic score) and myocardial injury biomarker (postoperative troponin I levels). Subgroup analyses were performed to assess the effect of modification and interaction. These included iNO dosage, the timing and duration of iNO therapy, different populations (children and adults), and comparators (other vasodilators and placebo or standard care). A comprehensive search for iNO and cardiac surgery was performed on online databases. Twenty-seven studies were included after removing the duplicates and irrelevant articles. The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.

Predictive Value of Serial Model of End-Stage Liver Disease Score Determination in Patients with Postcardiotomy Extracorporeal Membrane Oxygenation.

(1) Background: The use of extracorporeal membrane oxygenation (ECMO) in low cardiac output states after cardiac surgery may aid in patient recovery. However, in some patients, the clinical state may worsen, resulting in multiple organ failure and high mortality rates. In these circumstances, calculating a model of end-stage liver disease (MELD) score was shown to determine organ dysfunction and predicting mortality. (2) Methods: We evaluated whether serial MELD score determination increases mortality prediction in patients with postcardiotomy ECMO support. (3) Results: Statistically, a cutoff of a 2.5 MELD score increase within 48 h of ECMO initiation revealed an AUC of 0.722. Further, we found a significant association between hospital mortality and 48 h MELD increase (HR: 2.5, 95% CI: 1.33-4.75, p = 0.005) after adjustment for possible confounders. (4) Conclusions: Therefore, serial MELD score determinations on alternate days may be superior to single measurements in this special patient cohort.

Hemodynamic Determinants of Cardiac Surgery-Associated Acute Kidney Injury.

Examine the: 1) relative role of hemodynamic determinants of acute kidney injury (AKI) obtained in the immediate postcardiac surgery setting compared with established risk factors, 2) their predictive value, and 3) extent mediation via central venous pressure (CVP) and mean arterial pressure (MAP). Retrospective observational study. The main outcome of the study was moderate to severe AKI, per kidney disease: improving global outcomes, within 14 days of surgery. U.S. academic medical center. Adult patients undergoing cardiac surgery between January 2000 and December 2019 (n = 40,426) in a single U.S.-based medical center. Pulmonary artery catheter measurements were performed at a median of 102 minutes (11, 132) following cardiopulmonary bypass discontinuation. None. The median age of the cohort was 67 years (58, 75), and 33% were female; 70% had chronic hypertension, 29% had congestive heart failure, and 3% had chronic kidney disease. In a multivariable model, which included comorbidities and traditional intraoperative risk factors, CVP (p < 0.0001), heart rate (p < 0.0001), cardiac index (p < 0.0001), and MAP (p < 0.0001), were strong predictors of AKI, and superseded factors such as surgery type and cardiopulmonary bypass duration. The cardiac index had a significant interaction with heart rate (p = 0.026); a faster heart rate had a differentiating effect on the relationship of cardiac index with AKI, where a higher heart rate heightened the risk of AKI primarily in patients with low cardiac output. There was also significant interaction observed between CVP and MAP (p = 0.009); where the combination of elevated CVP and low MAP had a synergistic effect on AKI incidence. Hemodynamic factors measured within a few hours of surgery showed a strong association with AKI. Furthermore, determinants of kidney perfusion, namely CVP and arterial pressure are interdependent; as are constituents of stroke volume, that is, cardiac output and heart rate.

The cardiovascular changes underlying a low cardiac output with exercise in patients with type 2 diabetes mellitus.

The significant morbidity and premature mortality of type 2 diabetes mellitus (T2DM) is largely associated with its cardiovascular consequences. Focus has long been on the arterial atheromatosis of DM giving rise to early stroke and myocardial infarctions, whereas less attention has been given to its non-ischemic cardiovascular consequences. Irrespective of ischemic changes, T2DM is associated with heart failure (HF) most commonly with preserved ejection fraction (HFpEF). Largely due to increasing population ages, hypertension, obesity and T2DM, HFpEF is becoming the most prevalent form of heart failure. Unfortunately, randomized controlled trials of HFpEF have largely been futile, and it now seems logical to address the important different phenotypes of HFpEF to understand their underlying pathophysiology. In the early phases, HFpEF is associated with a significantly impaired ability to increase cardiac output with exercise. The lowered cardiac output with exercise results from both cardiac and peripheral causes. T2DM is associated with left ventricular (LV) diastolic dysfunction based on LV hypertrophy with myocardial disperse fibrosis and significantly impaired ability for myocardial blood flow increments with exercise. T2DM is also associated with impaired ability for skeletal muscle vasodilation during exercise, and as is the case in the myocardium, such changes may be related to vascular rarefaction. The present review discusses the underlying phenotypical changes of the heart and peripheral vascular system and their importance for an adequate increase in cardiac output. Since many of the described cardiovascular changes with T2DM must be considered difficult to change if fully developed, it is suggested that patients with T2DM are early evaluated with respect to their cardiovascular compromise.

The Lifesaving Impact of Transcatheter Interventions in the Early Post-Fontan Palliation Period.

Despite advancements in postoperative outcomes after Fontan surgery, there remains a risk of suboptimal outcomes and significant morbidity in the early postoperative period. Anatomical obstructions in the Fontan pathway can lead to prolonged pleural effusion or ascites, cyanosis, and low cardiac output syndrome (LCOS). Transcatheter interventions offer an alternative to early re-surgery for treating these complications. Over a 13-year period, early catheter angiography, performed within 30days post-index procedure, was administered to 41 patients, identifying anatomical issues that necessitated re-intervention in 39 cases. This led to transcatheter interventions in 37 (10.4%) of the 344 Fontan surgery patients. The median age was 4.8years (IQR: 4-9.4), and the median weight was 16.5kg (IQR: 15-25.2), with females comprising 51.4% (19/37) of this group. The primary indications for the procedures were persistent pleural effusion or ascites in 27 patients (66%), LCOS in 8 patients (20%), and cyanosis in 6 patients (14%). Among the 37 undergoing transcatheter intervention, 30 were treated solely with this method and discharged, three died in ICU follow-up, and four required early re-surgery. No procedural mortality was observed. Our findings demonstrate that transcatheter interventions, including stent implantation, balloon angioplasty, and fenestration dilation, are safe and effective in the early post-Fontan period. Therefore, they should be considered an integral part of the management strategy for this patient group.

Comparison of On-Pump Beating Heart Surgery Versus Conventional Bypass Surgery in Patients with Acute Myocardial Infarction Requiring Urgent Revascularization

Background: The objective of our study was to provide the initial outcomes of the traditional coronary artery surgery approach and the on-pump beating heart surgery in terms of survival and morbidity in patients who needed emergency surgery for acute myocardial infarction. Methods: A single-center retrospective study was performed from November 2013 to September 2023 on a total of 212 patients requiring emergency coronary artery surgery. Group I patients (n = 108) received traditional coronary artery bypass grafting with cross-clamping, while Group II patients (n = 104) underwent on-pump coronary surgery on the beating heart. Results: There were no disparities observed in the preoperative left ventricular function, percutaneous coronary intervention, intra-aortic balloon usage, or clinical-hemodynamic characteristics. Group I patients had significantly higher rates of postoperative mortality and low cardiac output syndrome, as well as a greater utilization of intra-aortic balloons and a higher requirement for extracorporeal membrane oxygenation (p &lt; 0.001). Conclusions: Ultimately, the on-pump beating heart approach could serve as a viable alternative to enhance the preservation of cardiac function and decrease postoperative complications and mortality rates in patients with acute myocardial infarction who require emergency surgery.

Lactate infusion elevates cardiac output through increased heart rate and decreased vascular resistance: a randomised, blinded, crossover trial in a healthy porcine model

BackgroundLactate is traditionally recognized as a by-product of anaerobic metabolism. However, lactate is a preferred oxidative substrate for stressed myocardium. Exogenous lactate infusion increases cardiac output (CO). The exact mechanism underlying this mechanism has yet to be elucidated. The aim of this study was to investigate the cardiovascular mechanisms underlying the acute haemodynamic effects of exogenous lactate infusion in an experimental model of human-sized pigs.MethodsIn this randomised, blinded crossover study in eight 60-kg-pigs, the pigs received infusions with one molar sodium lactate and a control infusion of tonicity matched hypertonic saline in random order. We measured CO and pulmonary pressures using a pulmonary artery catheter. A pressure–volume admittance catheter in the left ventricle was used to measure contractility, afterload, preload and work-related parameters.ResultsLactate infusion increased circulating lactate levels by 9.9 mmol/L (95% confidence interval (CI) 9.1 to 11.0) and CO by 2.0 L/min (95% CI 1.2 to 2.7). Afterload decreased as arterial elastance fell by -1.0 mmHg/ml (95% CI -2.0 to -0.1) and systemic vascular resistance decreased by -548 dynes/s/cm5 (95% CI -261 to -835). Mixed venous saturation increased by 11 percentage points (95% CI 6 to 16), whereas ejection fraction increased by 16.0 percentage points (95% CI 1.1 to 32.0) and heart rate by 21 bpm (95% CI 8 to 33). No significant changes in contractility nor preload were observed.ConclusionLactate infusion increased cardiac output by increasing heart rate and lowering afterload. No differences were observed in left ventricular contractility or preload. Lactate holds potential as a treatment in situations with lowered CO and should be investigated in future clinical studies.Graphical

A study on the outcome of preoperative pulmonary function tests on a patient undergoing rheumatic mitral valve surgery.

Evaluation of pulmonary function by spirometer in adult patients undergoing cardiac surgery is a simple test to assess pulmonary reserve that has important implications in operative morbidity. However, there is no established consensus regarding which patients should undergo preoperative pulmonary function tests (PFTs), including forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC). The primary aim was to evaluate the outcome of preoperative PFTs on patients undergoing rheumatic mitral valve surgery. One hundred patients undergoing rheumatic mitral valve surgery, meeting the inclusion criteria, were included in this prospective observational study. The pulmonary function of the patients was assessed using a spirometer before surgery. Preoperative pulmonary artery systolic pressure (PASP) and arterial blood gas (ABG) analyses were also performed. The correlation of PFTs with early postsurgical outcome, comprising mortality within 30 days of surgery and morbidity defined as the existence of at least one of the postoperative complications, such as low cardiac output state indicated by increased requirement of inotropes, prolonged ventilation (>24 hours), postoperative new-onset hemodynamically significant arrhythmias, renal dysfunction, and post-op infection, was assessed. With the increasing New York Heart Association (NYHA) class of the patient, there was a decline of FEV1% and FVC%, which was statistically significant (P < 0.0001). There was a significant positive correlation of FVC% with preoperative saturation of peripheral oxygen (SpO2) and preoperative saturation of peripheral carbon dioxide (PaO2) and FEV1% with preoperative SpO2 and preoperative PaO2. Patients who had postoperative prolonged ventilation had lower values of FVC% and FEV1%, which was statistically significant (P < 0.001). The patients who expired had significantly lower values of FVC% and FEV1%. Preoperative lung function has an implication on intraoperative morbidity during cardiac surgery although a common consensus on its application is lacking. Preoperative spirometry can be one of the parameters for predicting postoperative morbidity and mortality in patients undergoing rheumatic mitral valve surgery. Spirometry might have a role to play in predicting patient outcomes in rheumatic mitral valve surgeries; however, larger well-powered studies are needed.

Impact of Hemoglobin Level in Ex Vivo Heart Perfusion on Donation After Circulatory Death Hearts: A Juvenile Porcine Experimental Model.

Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t -tests or Fisher's Exact tests. During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption ( P < 0.001), a higher arterial lactate level ( P = 0.001), and worse systolic ventricular function ( P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level ( P = 0.031). Adjusted cardiac troponin-I ( P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group ( P = 0.028). Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.

Prognostic impact of combined non-severe aortic stenosis and mitral regurgitation on clinical outcomes: a single-centre retrospective study

ObjectivesThough the concomitant occurrence of non-severe aortic stenosis (AS) and mitral regurgitation (MR) is highly prevalent, there are limited data to guide clinical decision-making in this condition. Here, we attempt...

Anisocytosis as a possible predictor of low cardiac output syndrome in children undergoing mitral valve surgery

PurposeMitral valve surgery in children involves correcting congenital and acquired pathologies, with a reported mortality rate of 0.9%. Low cardiac output syndrome (LCOS) is a serious complication with the incidence of 20–25%. The aim of the study was to estimate possible prognostic factors of LCOS in children undergoing mitral valve procedure. Material and methodThis single-center retrospective analysis enrolled children aged <18 years who underwent mitral valve surgery during 24 year period. Preoperative clinical and laboratory parameters, and operative factors were analyzed. ResultsThirty consecutive pediatric patients (11 (37%) males and 19 (63%) females) in median (Q1 – Q3) age of 57 (25–115) months, who underwent mitral valve replacement, were included. The 30-day mortality was 7% (2 patients) and was related to postoperative multiorgan failure. LCOS occurred in 8 (27%) children. The receiver operator curve (ROC) analysis established parameters that have predictive value for LCOS occurrence: cardiopulmonary bypass (CPB) time, with 89 ​min as optimal cut-off point (AUC ​= ​0.744, p ​= ​0.011) yielding sensitivity of 100% and specificity of 42.9%; left ventricular ejection fraction (LVEF) ​< ​60 % (AUC ​= ​0.824, okp ​= ​0.001) with sensitivity of 62.5% and specificity of 93.75%; and red blood cell distribution width (RDW) above 14.5 % (AUC ​= ​0.840, p ​< ​0.001; sensitivity of 87.5% and specificity of 75%). ConclusionsIn mitral valve replacement in pediatric patients, CPBtime above 89 ​min, preoperative LVEF below 60% and preoperative RDW above 14.5% can be regarded as the potential predictors of LCOS.

Efficacy and Safety of Multidose del Nido Cardioplegia for Optimal Myocardial Protection in Isolated Coronary Artery Bypass Grafting Surgery: A Comparative Retrospective Cohort Study

Background: The perioperative outcomes of del Nido cardioplegia (DNC) as a single-dose solution have been investigated in cardiac surgical procedures. However, the optimal redosing interval for multiple doses of DNC remains an area of ongoing debate. The purpose of this study is to evaluate the safety and efficacy of multidose DNC administered according to our protocol in comparison to intermittent cold blood cardioplegia (BC) in isolated coronary artery bypass grafting (CABG) patients. Methods: A retrospective analysis was conducted on 79 consecutive isolated CABG patients between January 2022 and March 2023. The Patients were divided into two groups: the DNC group (n = 35), and the BC group (n = 44). Perioperative clinical characteristics, cardiac enzyme levels, and postoperative complications were compared between the groups. DNC was applied in a 1:4 (crystalloid:blood) ratio, with an initial dose of 20 mL/kg. Maintenance doses of 10 mL/kg were given every 45 to 50 minutes. A half dose was given if the aortic cross-clamp was expected to last less than 60 minutes. Warm blood was applied before releasing the aortic cross-clamp. Results: Both groups demonstrated comparable mean aortic cross-clamp and cardiopulmonary bypass times. At 24 hours postoperatively, troponin T levels were significantly lower in the DNC group (p ˂ 0.001), while creatine kinase-myocardial band (CK-MB) levels were higher (p ˂ 0.001). The DNC group required lower defibrillation rates than the BC group (p = 0.008). Multivariate logistic regression analysis revealed that the requirement for defibrillation (odds ratio (OR) = 10.9, 95% confidence interval (CI): 2.9–41.8, p &lt; 0.001), cross-clamp time (OR = 1.04, 95% CI: 1.02–1.1, p = 0.002) and body mass index (BMI) (OR = 0.8, 95% CI: 0.7–0.9, p = 0.030) were independent risk factors for low cardiac output syndrome. DNC and left ventricle ejection fraction &gt;40% were associated with a return to sinus rhythm (OR = 3.6, 95% CI: 1.3–10.1, p = 0.013 and OR = 3.1, 95% CI: 1.1–8.7, p = 0.035, respectively). No significant differences were found in terms of postoperative adverse events, and in-hospital mortality. Conclusion: Multidose DNC in CABG patients provides equivalent clinical outcomes and myocardial protection compared to BC. In addition, the findings suggest that the redosing interval strategy employed in the DNC protocol is acceptable.

In silico parametric analysis of femoro-jugular venovenous ECMO and return cannula dynamics

Background: Increasingly, computational fluid dynamics (CFD) is helping explore the impact of variables like: cannula design/size/position/flow rate and patient physiology on venovenous (VV) extracorporeal membrane oxygenation (ECMO). Here we use a CFD model to determine what role cardiac output (CO) plays and to analyse return cannula dynamics. Methods: Using a patient-averaged model of the right atrium and venae cava, we virtually inserted a 19Fr return cannula and a 25Fr drainage cannula. Running large eddy simulations, we assessed cardiac output at: 3.5–6.5 L/min and ECMO flow rate at: 2–6 L/min. We analysed recirculation fraction (Rf), time-averaged wall shear stress (TAWSS), pressure, velocity, and turbulent kinetic energy (TKE) and extracorporeal flow fraction (EFF = ECMO flow rate/CO). Results: Increased ECMO flow rate and decreased CO (high EFF) led to increased Rf (R = 0.98, log fit). Negative pressures developed in the venae cavae at low CO and high ECMO flow (high CR). Mean return cannula TAWSS was >10 Pa for all ECMO flow rates, with majority of the flow exiting the tip (94.0–95.8 %). Conclusions: Our results underpin the strong impact of CO on VV ECMO. A simple metric like EFF, once supported by clinical data, might help predict Rf for a patient at a given ECMO flow rate. The return cannula imparts high shear stresses on the blood, largely a result of the internal diameter.

Long-term survival after surgical treatment for post-infarction mechanical complications: results from the Caution study.

Mechanical complications (MCs) are rare but potentially fatal sequelae of acute myocardial infarction (AMI). Surgery, though challenging, is considered the treatment of choice. The authors sought to study early and long-term results of patients undergoing surgical treatment for post-AMI MCs. Patients undergone surgical treatment for post-infarction MCs between 2001 through 2019 in 27 centers worldwide were retrieved from the database of CAUTION study. In-hospital and long-term mortality were the primary outcomes. Cox proportional hazards regression models were used to determine independent factors associated with overall mortality. The study included 720 patients. The median age was 70.0 [62.0-77.0] years, with a male predominance (64.6%). The most common MC encountered was ventricular septal rupture (VSR) (59.4%). Cardiogenic shock was seen on presentation in 56.1% of patients. In-hospital mortality rate was 37.4%; in more than 50% of cases, the cause of death was low cardiac output syndrome (LCOS). Late mortality occurred in 133 patients, with a median follow-up of 4.4 [1.0-8.6] years. Overall survival at 1, 5 and 10 years was 54.0%, 48.1% and 41.0%, respectively. Older age (p<0.001) and postoperative LCOS (p<0.001) were independent predictors of overall mortality. For hospital survivors, 10-year survival was 65.7% and was significant higher for patients with VSR than those with papillary muscle rupture (long-rank P=0.022). Contemporary data from a multicenter cohort study show that surgical treatment for post-AMI MCs continues to be associated with high in-hospital mortality rates. However, long-term survival in patients surviving the immediate postoperative period is encouraging.Trial registration number: NCT03848429.

ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection.

Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signalling, cardiomyocytes counteract infection by various effector processes, with the IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification with ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular aspects how the ISG15 system affects the functional properties of respective protein substrates in the heart are unknown. Based on the protective properties due to protein ISGylation, we set out a study investigating CVB3-infected mice in depth and found cardiac atrophy with lower cardiac output in ISG15-/- mice. By mass spectrometry, we identified the protein targets of the ISG15 conjugation machinery in heart tissue and explored how ISGylation affects their function. The cardiac ISGylome showed a strong enrichment of ISGylation substrates within glycolytic metabolic processes. Two control enzymes of the glycolytic pathway, hexokinase 2 (HK2) and phosphofructokinase muscle form (PFK1), were identified as bona fide ISGylation targets during infection. In an integrative approach complemented with enzymatic functional testing and structural modelling, we demonstrate that protein ISGylation obstructs the activity of HK2 and PFK1. Seahorse-based investigation of glycolysis in cardiomyocytes revealed that, by conjugating proteins, the ISG15 system prevents the infection-/IFN-induced up-regulation of glycolysis. We complemented our analysis with proteomics-based advanced computational modelling of cardiac energy metabolism. Our calculations revealed an ISG15-dependent preservation of the metabolic capacity in cardiac tissue during CVB3 infection. Functional profiling of mitochondrial respiration in cardiomyocytes and mouse heart tissue by Seahorse technology showed an enhanced oxidative activity in cells with a competent ISG15 system. Our study demonstrates that ISG15 controls critical nodes in cardiac metabolism. ISG15 reduces the glucose demand, supports higher ATP production capacity in the heart, despite nutrient shortage in infection, and counteracts cardiac atrophy and dysfunction.

Technical performance scores associate with early prognosis of tetralogy of Fallot repair.

This study aimed to investigate the relationship between technical performance scores (TPS) and the early prognosis of tetralogy of Fallot repair (TOF). A retrospective study was conducted on TOF repair patients at our center from Oct 2017 to Oct 2022. Patients were classified into Class 1 (no residua), Class 2 (minor residua), or Class 3 (major residua) based on TPS derived from predischarge echocardiograms and need for reintervention. Statistical methods were used to assess the association between TPS and early prognosis. A total of 75 TOF repair patients (40% female, 60% male) were analyzed and categorized into TPS1 (24%), TPS2 (53.3%), and TPS3 (22.6%) based on pre-discharge echocardiographic findings. The median follow-up time was 7.0 months. The multivariable Cox regression analysis indicated that TPS3 scores are associated with a 12.68-fold increase in risk compared to TPS1 and TPS2 scores [95% CI = 12.68 (0.9∼179.28), P = 0.06]. The Spearman rank correlation analysis revealed a weak positive correlation between TPS classification and low cardiac output syndrome (r = 0.26, P = 0.03). However, there were no significant differences in ICU stay or duration of mechanical ventilation among the groups. TPS3 after intracardiac TOF repair is associated with higher risk of early re-intervention, highlighting the importance of close follow-up and monitoring in this patient population. Patients who develop low cardiac output syndrome in the early postoperative period may have residual defects that require prompt identification.

Deep phenotyping of p.(V142I)-associated variant transthyretin amyloid cardiomyopathy: Distinct from wild-type transthyretin amyloidosis?

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. A total of 3-4% of individuals of African descent carry a TTR gene mutation encoding the p.(V142I) variant, a powerful risk factor for development of variant ATTR-CM (ATTRv-CM); this equates to 1.6 million carriers in the United States. We undertook deep phenotyping of p.(V142I)-ATTRv-CM and comparison with wild-type ATTR-CM (ATTRwt-CM). A retrospective study of 413 patients with p.(V142I) ATTRv-CM who attended the UK National Amyloidosis Centre (NAC) was conducted. Patients underwent evaluation at time of diagnosis, including clinical, echocardiography, and biomarker analysis; a subgroup had cardiac magnetic resonance (CMR) imaging. A total of 413 patients with ATTRwt-CM, matched for independent predictors of prognosis (age, NAC Stage, decade of first presentation), were used as a comparator group. At time of diagnosis, patients with ATTRv-CM had significant functional impairment by New York Heart Association classification (NHYA class ≥ III; 38%) and 6-min walk test distance (median 276 m). Median 5-year survival in ATTRv-CM patients was 31 versus 59 months in matched patients with ATTRwt-CM (p < 0.001). Patients with ATTRv-CM had significant impairment of functional parameters by echocardiography including biventricular impairment, high burden of regurgitant valvular disease and low cardiac output. Multivariable analysis revealed the prognostic importance of right ventricular dysfunction. CMR and histological analysis revealed myocyte atrophy and widespread myocardial infiltration in ATTRv-CM. p.(V142I)-ATTRv-CM has an aggressive phenotype characterized by myocyte loss and widespread myocardial infiltration which may account for frequent biventricular failure and poor prognosis in this ATTR-CM genotypic subgroup.