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Gene and metabolite expression dependence on body mass index in human myocardium.
Adebayo, AS, Roman, M, Zakkar, M, Yusoff, S, Gulston, M, Joel-David, L, Anthony, B, Lai, FY, Murgia, A, Eagle-Hemming, B, et al
Scientific reports. 2022;(1):1425
Abstract
We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI < 25, 25 ≤ BMI ≤ 32, and BMI > 32. The analysis indicated that protein translation-related pathways were downregulated in 25 ≤ BMI ≤ 32 compared with BMI < 25 patients. Muscle contraction transcripts were upregulated in 25 ≤ BMI ≤ 32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI > 32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI > 32 group and α-ketoglutarate increasing in the BMI < 25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.
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Comparison of Microplegia Solution and Del Nido Cardioplegia Solution in Coronary Artery Bypass Grafting Surgery: Which One is More Effective?
Urcun, YS, Pala, AA
The heart surgery forum. 2021;(5):E842-E848
Abstract
BACKGROUND The aim of this study is to compare the efficacy of the microplegia solution and Del Nido cardioplegia solution in coronary artery bypass surgery with clinical, biochemical, and echocardiographic data. METHODS Three hundred patients, who underwent coronary artery bypass surgery between January 2017 and January 2020, by the same surgical team were included in the study. Preoperative, operative and postoperative data (cardiac biomarker levels, cross-clamp and CPB times, echocardiographic measurements, etc.) of the patients were compared. RESULTS In the study, cross-clamp time was significantly shorter in the DN cardioplegia group (55.60 ± 13.49 min/75.58 ± 12.43 min, P = 0.024). No significant difference was observed between the two groups in terms of intensive care stay, extubation time, hospital stay, and cardiopulmonary bypass time. In our study, it was shown that both the left and right ventricular ejection fraction was better protected in the Del Nido cardioplegia group (5.34±3.03 vs. 3.40±2.84, P = 0.017 and 3.82±1.19 vs. 2.28±1.87, P = 0.047, respectively), and the need for inotrope support was lower in this group (28% vs. 44%, P < 0.021). There was no significant difference between the groups, in terms of blood transfusion rates, IABP requirement. CONCLUSION In light of short-term results, we can say that Del Nido cardioplegia provides better myocardial protection than microplegia. In addition, Del Nido cardioplegia can be given as a single dose for 90 minutes of cross-clamp time and therefore can be preferred to increase surgical comfort and reduce cross-clamp times.
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Effects of Del Nido and Terminal Warm Blood Cardioplegia on Myocardial Protection and Rhythm in Isolated CABG Patients.
Karaarslan, K, Abud, B
The heart surgery forum. 2021;(5):E808-E813
Abstract
OBJECTIVE To investigate the effect of using del Nido cardioplegia+terminal hot-shot blood cardioplegia on myocardial protection and rhythm in isolated coronary bypass patients. MATERIAL AND METHODS A total of 122 patients were given cold (+4-8C') del Nido cardioplegia antegrade and evaluated. Del Nido+terminal warm blood cardioplegia (TWBCP) was applied to 63 patients out of 122 patients, while del Nido cardioplegia alone was applied to the other 59 patients. The preoperative and postoperative data of the patients were recorded and compared. RESULTS There was a significant statistical difference between the groups, in terms of volume with more cardioplegia in the del Nido+terminal warm blood cardioplegia group. Although there was no significant difference between cardiac arrest times in both groups, a statistically significant difference was found in the del Nido+terminal warm blood cardioplegia group in the starting to work time of the heart. No difference found between the groups regarding myocardial preservation. CONCLUSIONS We can add a return to spontaneous sinus rhythm to the advantages of terminal warm blood cardioplegia and del Nido cardioplegia in literature. We think it would be a good strategy to extend the safe ischemic time limit of del Nido to 120 minutes with a terminal warm blood cardioplegia. It seems that cardioplegia techniques that will be developed by adding the successful and superior results of crystalloid cardioplegia applications, such as single dose del Nido in various open heart surgery operations and the superior myocardial return effects of terminal warm blood cardioplegia, will be used routinely in the future.
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Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study.
van Groenendael, R, Beunders, R, Hemelaar, P, Hofland, J, Morshuis, WJ, van der Hoeven, JG, Gerretsen, J, Wensvoort, G, Kooistra, EJ, Claassen, WJ, et al
Critical care medicine. 2021;(5):790-803
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Abstract
OBJECTIVES To determine the safety and efficacy of human chorionic gonadotropin hormone-derivative EA-230 in cardiac surgery patients. Cardiac surgery induces systemic inflammation and may impair renal function, affecting patient outcome. EA-230 exerted immunomodulatory and renoprotective effects in preclinical models and was safe and showed efficacy in phase I and II human studies. DESIGN Double-blinded, placebo-controlled, randomized study. SETTING Collaboration of the Cardiothoracic Surgery, Anesthesiology, and the Intensive Care departments of a tertiary hospital in the Netherlands. PATIENTS One hundred eighty patients undergoing an on-pump coronary artery bypass procedure with or without concomitant valve surgery. INTERVENTIONS Ninety mg/kg/hr EA-230 or placebo administered during surgery. MEASUREMENTS AND MAIN RESULTS During the study, no safety concerns emerged. EA-230 did not modulate interleukin-6 plasma concentrations (area under the curve 2,730 pg/mL × hr [1,968-3,760] vs 2,680 pg/mL × hr [2,090-3,570] for EA-230 and placebo group, respectively; p = 0.80). Glomerular filtration rate increased following surgery (mean ± sem increase in the EA-230 vs placebo groups: glomerular filtration rateiohexol measured using iohexol plasma clearance: 19 ± 2 vs 16 ± 2 mL/min/1.73 m2; p = 0.13 and estimated glomerular filtration rate with the Modification of Diet in Renal Disease equation using creatinine: 6 ± 1 vs 2 ± 1 mL/min/1.73 m2; p = 0.01). The "injury" stage of the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria for acute kidney injury was 7% in the EA-230 group versus 18% in the placebo group (p = 0.07). In addition, EA-230-treated patients had a less positive fluid balance compared with placebo-treated patients (217 ± 108 vs 605 ± 103 mL; p = 0.01), while the use of vasoactive agents was similar in both groups (p = 0.39). Finally, hospital length of stay was shorter in EA-230 treated patients (8 d [7-11] vs 10 d [8-12]; p = 0.001). Efficacy results were more pronounced in patients that had longer duration of surgery and thus longer duration of study drug infusion. CONCLUSIONS EA-230 was safe in patients undergoing on-pump cardiac surgery. It did not modulate interleukin-6 plasma concentrations but appeared to exert beneficial renal and cardiovascular effects and shortened in-hospital length of stay.
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Perioperative Risk Factors Predisposing to Atrial Fibrillation After CABG Surgery.
Omar, A, Ehab M Elshihy, , Mahmoud Singer, , David Zarif, , Omar Dawoud,
The heart surgery forum. 2021;(2):E402-E406
Abstract
OBJECTIVES To detect perioperative risk factors for atrial fibrillation (AF) after coronary artery bypass graft (CABG) and to assess the impact of AF on outcome and postoperative complications. METHODS We undertook a prospective observational study of 1000 consecutive patients who underwent isolated CABG in Cairo University hospitals and other centers from March 2019 to November 2020. Patients were subsequently divided into 2 groups depending on the occurrence of postoperative AF. Preoperative, intraoperative, and postoperative risk factors were recorded for all patients, as well as postoperative mortality, complications, and hospital and intensive care unit (ICU) lengths of stay. RESULTS Postoperative atrial fibrillation (POAF) occurred in 78 patients (7.8%), with significant risk factors of age (P = .001), low ejection fraction (P = .001), absence of preoperative beta-blocker use (P = .001), and presence of right coronary artery lesion (P = .003). The intraoperative significant risk factor was the absence of total coronary revascularization (P = .001). Postoperative significant risk factors were electrolyte imbalance (P = .001) and postoperative inotropes (P = .02). Patients with postoperative AF had increased risk of mortality (P = .001) and longer ICU (P = .001) and hospital (P = .001) stays. CONCLUSION The risk of POAF can be decreased by modifying perioperative adjustable risk factors, namely routinely using preoperative beta-blockers (unless contraindicated), achieving total coronary revascularization, avoiding postoperative electrolyte imbalance, and avoiding unnecessary use of inotropic support.
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Clinically inapparent right heart dysfunction is associated with reduced myofilament force development in coronary artery disease.
Bening, C, Sales, VL, Alhussini, K, Radakovic, D, Benitez, RC, Madrahimov, N, Keller, D, Leyh, R
BMC cardiovascular disorders. 2021;(1):125
Abstract
BACKGROUND Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We aimed to identify clinical and experimental predictors for preoperative inapparent right ventricular dysfunction and therefore hypothesized that reduced myofilament force development as well as altered levels of biomarkers might predict inapparent right ventricular dysfunction. METHODS From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥ 20 mm, n = 178; TAPSE < 20 mm, n = 40). Baseline serum samples for biomarkers (Galectin, TGFß1, N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements. RESULTS Patients with TAPSE < 20 mm had a higher incidence of DM (55 vs. 34%, p = 0.018), preoperative AFib (43 vs. 16%, p < 0.001), reduced GFR (67 ± 18 vs. 77 ± 24 ml/min/1.73 m2, p = 0.013), larger LA area (22 ± 6 vs. 20 ± 5 cm2, p = 0.005) and reduced LVEF (50 vs. 55%, p = 0.008). Furthermore, higher serum ADMA (0.70 ± 0.13 vs. 0.65 ± 0.15 µmol/l, p = 0.046) and higher serum Pentraxin-3 levels (3371 ± 1068 vs. 2681 ± 1353 pg/dl, p = 0.004) were observed in these patients. Skinned fiber force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5, p < 0.01 and pCa 5.75-6.0, p < 0.05). Multivariable analysis revealed DM (OR 2.53, CI 1.12-5.73, Euro Score II (OR 1.34, CI 1.02-1.78), preoperative AF (OR 4.86, CI 2.06-11.47), GFR (OR 7.72, CI 1.87-31.96), albumin (OR 1.56, CI 0.52-2.60), Pentraxin-3 (OR 19.68, CI 14.13-25.24), depressed LVEF (OR 8.61, CI 6.37-10.86), lower force values: (pCa 5.4; OR 2.34, CI 0.40-4.29 and pCa 5.2; OR 2.00, CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. CONCLUSIONS These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.
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Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons.
Chaitman, BR, Alexander, KP, Cyr, DD, Berger, JS, Reynolds, HR, Bangalore, S, Boden, WE, Lopes, RD, Demkow, M, Piero Perna, G, et al
Circulation. 2021;(8):790-804
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Abstract
BACKGROUND In the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality in comparison with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular end points was myocardial infarction (MI). METHODS ISCHEMIA prespecified that the primary and major secondary composite end points of the trial be analyzed using 2 MI definitions. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times the upper reference level for percutaneous coronary intervention and >10 times for coronary artery bypass grafting. Procedural MI definitions included (1) a category of elevated biomarker only events with much higher biomarker thresholds, (2) new ST-segment depression of ≥1 mm for the primary and ≥0.5 mm for the secondary definition, and (3) new coronary dissections >National Heart, Lung, and Blood Institute grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions. RESULTS Procedural MIs accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive versus conservative strategy using the primary (2.7% versus 1.1%; adjusted hazard ratio [HR], 2.98 [95% CI, 1.87-4.73]) and secondary (8.2% versus 2.0%; adjusted HR, 5.04 [95% CI, 3.64-6.97]) MI definitions. Type 1 MIs were less frequent with the invasive versus conservative strategy using the primary (3.40% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) and secondary (3.48% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) definitions. The risk of subsequent cardiovascular death was higher after a type 1 MI than after no MI using the primary (adjusted HR, 3.38 [95% CI, 2.03-5.61]; P<0.001) or secondary MI definition (adjusted HR, 3.52 [2.11-5.88]; P<0.001). CONCLUSIONS In ISCHEMIA, type 1 MI events using the primary and secondary definitions during 5-year follow-up were more frequent with an initial conservative strategy and associated with subsequent cardiovascular death. Procedural MI rates were greater in the invasive strategy and with the use of the secondary MI definition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
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Effects of inorganic nitrate on ischaemia-reperfusion injury after coronary artery bypass surgery: a randomised controlled trial.
Eriksson, KE, Eidhagen, F, Liska, J, Franco-Cereceda, A, Lundberg, JO, Weitzberg, E
British journal of anaesthesia. 2021;(4):547-555
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Abstract
BACKGROUND Nitric oxide (NO) is an important signalling molecule in the cardiovascular system with protective properties in ischaemia-reperfusion injury. Inorganic nitrate, an oxidation product of endogenous NO production and a constituent in our diet, can be recycled back to bioactive NO. We investigated if preoperative administration of inorganic nitrate could reduce troponin T release and other plasma markers of injury to the heart, liver, kidney, and brain in patients undergoing cardiac surgery. METHODS This single-centre, randomised, double-blind, placebo-controlled trial included 82 patients undergoing coronary artery bypass surgery with cardiopulmonary bypass. Oral sodium nitrate (700 mg×2) or placebo (NaCl) were administered before surgery. Biomarkers of ischaemia-reperfusion injury and plasma nitrate and nitrite were collected before and up to 72 h after surgery. Troponin T release was our predefined primary endpoint and biomarkers of renal, liver, and brain injury were secondary endpoints. RESULTS Plasma concentrations of nitrate and nitrite were elevated in nitrate-treated patients compared with placebo. The 72-h release of troponin T did not differ between groups. Other plasma biomarkers of organ injury were also similar between groups. Blood loss was not a predefined outcome parameter, but perioperative bleeding was 18% less in nitrate-treated patients compared with controls. CONCLUSION Preoperative administration of inorganic nitrate did not influence troponin T release or other plasma biomarkers of organ injury in cardiac surgery. CLINICAL TRIAL REGISTRATION NCT01348971.
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Comparison of Percutaneous Coronary Intervention, Coronary Artery Bypass Grafting and Medical Therapy in Non-ST Elevation Acute Coronary Syndrome Patients With 3-Vessel Disease.
Jia, S, Zhang, C, Jiang, L, Xu, L, Tian, J, Zhao, X, Feng, X, Wang, D, Zhang, Y, Sun, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2020;(10):1718-1727
Abstract
BACKGROUND The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P<0.05). Compared with MT, PCI and CABG had lower incidences of all adverse outcomes (all P<0.05), except for a similar rate of stroke between PCI and MT. Kaplan-Meier analysis showed similar results. After adjusting for confounders, CABG was independently associated with a lower risk of cardiac death, revascularization and MACCE compared with PCI (all P<0.05). Compared with MT, PCI reduced long-term risk of death, whereas CABG reduced long-term risk of death, revascularization and MACCE events (all P<0.05). CONCLUSIONS In NSTE-ACS patients with 3VD, CABG is independently associated with a lower risk of long-term cardiac death, revascularization and MACCE compared with PCI. Patients who received MT alone had the highest risk of long-term MACCE.
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Effects of high-dose vitamin D supplementation on the occurrence of post-operative atrial fibrillation after coronary artery bypass grafting: randomized controlled trial.
Kara, H, Yasim, A
General thoracic and cardiovascular surgery. 2020;(5):477-484
Abstract
OBJECTIVE This study aimed to investigate the preventive effects of a high-dose vitamin D administered preoperatively on the post-operative atrial fibrillation (POAF) occurrence in patients with insufficient or deficient serum vitamin D levels who underwent coronary artery bypass grafting (CABG) surgery. METHODS The study was a randomized controlled, blinded and parallel-arm trial conducted on 116 who had vitamin D deficiency or insufficiency during the pre-operative evaluation were included in the study conducted between January 2018 and January 2019. Patients were divided into those who received oral vitamin D (treatment group; n = 58) and those who did not (control group; n = 58) 48 h before CABG surgery. In the treatment group, patients with vitamin D deficiency were administered 300.000 IU vitamin D orally and those with vitamin D insufficiency 150.000 IU 48 h preoperatively. Patients were followed up during hospitalisation process with respect to POAF. RESULTS Both groups showed no significant differences with regard to age, gender, body mass index, creatine level, left atrial diameter, pre-operative drug use, calcium level, ejection fraction, diabetes mellitus and hypertension. The ratio of POAF occurrence found in the treatment and control groups were 12.07% and 27.59%, respectively. Vitamin D treatment was found to reduce the risk of POAF development by 0.24 times (p = 0.034). CONCLUSION In this study with sufficient sample size, preoperative short-term high-dose vitamin D supplementation was found to be significantly preventive to the occurrence of POAF in patients with vitamin D insufficiency and deficiency who underwent CABG surgery.