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Myocardial protective effect of intracoronary administration of nicorandil and alprostadil via targeted perfusion microcatheter in patients undergoing elective percutaneous coronary intervention: A randomized controlled trial.
Zhang, W, Dai, J, Zheng, X, Xu, K, Yang, X, Shen, L, Wang, X, Hao, Z, Qiu, X, Jiang, L, et al
Medicine. 2021;(15):e25551
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BACKGROUND The aim of the study was to evaluate the efficacy of nicorandil and alprostadil on myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI). METHODS In this prospective, single-blinded, randomized controlled study, 90 consecutive patients scheduled for elective PCI for de novo coronary lesions were assigned to the nicorandil, alprostadil, and nitroglycerin groups in a 1:1:1 ratio. Drugs were administered intracoronary via a targeted perfusion microcatheter. The primary endpoint was the thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC). Additionally, the corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), and incidence of periprocedural myocardial injury (PMI) were assessed. RESULTS Both nicorandil and alprostadil were significantly effective in reducing TMPFC (114.6 ± 33.7 vs 93.4 ± 30.9, P = .016; 114.3 ± 34.3 vs 94.7 ± 33.3, P = .029, respectively). Similar findings were observed in the improvement of cTFC (20.3 ± 10.5 vs 13.5 ± 5.0, P = .003; 20.2 ± 7.4 vs 15.2 ± 5.2, P = .003, respectively) and percentage of TMPG 3 (100% vs 82.8%, P = .052; 83.3% vs 96.7%, P = .196, respectively); whereas, nitroglycerin produced a limited effect on TMPFC (114.4 ± 30.9 vs 112.1 ± 31.9, P = .739), cTFC (19.4 ± 7.2 vs 19.3 ± 7.2, P = .936), and percentage of TMPG 3 (86.7% vs 86.7%, P = 1.000). No significant difference was found in the incidence of PMI (16.7% vs 16.0% vs 27.6%, P = .537), though it was comparatively lower in the nicorandil and alprostadil groups. Furthermore, the intracoronary administration of nicorandil and alprostadil had a mild effect on blood pressure and heart rate. CONCLUSIONS The intracoronary administration of nicorandil and alprostadil via a targeted perfusion microcatheter was more effective in improving myocardial perfusion in patients undergoing elective PCI than nitroglycerin.
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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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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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Cardiovascular Benefit of Empagliflozin Across the Spectrum of Cardiovascular Risk Factor Control in the EMPA-REG OUTCOME Trial.
Inzucchi, SE, Khunti, K, Fitchett, DH, Wanner, C, Mattheus, M, George, JT, Ofstad, AP, Zinman, B
The Journal of clinical endocrinology and metabolism. 2020;(9):3025-35
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CONTEXT Control of multiple cardiovascular (CV) risk factors reduces CV events in individuals with type 2 diabetes. OBJECTIVE To investigate this association in a contemporary clinical trial population, including how CV risk factor control affects the CV benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor. DESIGN Post hoc analysis. SETTING Randomized CV outcome trial (EMPA-REG OUTCOME). PARTICIPANTS Type 2 diabetes patients with established CV disease. INTERVENTION Empagliflozin or placebo. MAIN OUTCOME MEASURES Risk of CV outcomes-including the treatment effect of empagliflozin-by achieving 7 goals for CV risk factor control at baseline: (1) glycated hemoglobin <7.5%, (2) low-density lipoprotein cholesterol <100 mg/dL or statin use, (3) systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg, (4) pharmacological renin-angiotensin-aldosterone system blockade, (5) normoalbuminuria, (6) aspirin use, (7) nonsmoking. RESULTS In the placebo group, the hazard ratio (HR) for CV death was 4.00 (95% CI, 2.26-7.11) and 2.48 (95% CI, 1.52-4.06) for patients achieving only 0-3 or 4-5 risk factor goals at baseline, respectively, compared with those achieving 6-7 goals. Participants achieving 0-3 or 4-5 goals also had increased risk for the composite outcome of hospitalization for heart failure or CV death (excluding fatal stroke) (HR 2.89 [1.82-4.57] and 1.90 [1.31-2.78], respectively) and 3-point major adverse CV events (HR 2.21 [1.53-3.19] and 1.42 [1.06-1.89]). Empagliflozin significantly reduced these outcomes across all risk factor control categories (P > 0.05 for treatment-by-subgroup interactions). CONCLUSIONS Cardiovascular risk in EMPA-REG OUTCOME was inversely associated with baseline CV risk factor control. Empagliflozin's cardioprotective effect was consistent regardless of multiple baseline risk factor control.
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Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study.
Benlloch, M, Cuerda Ballester, M, Drehmer, E, Platero, JL, Carrera-Juliá, S, López-Rodríguez, MM, Ceron, JJ, Tvarijonaviciute, A, Navarro, MÁ, Moreno, ML, et al
Nutrients. 2020;(12)
Abstract
Multiple sclerosis (MS) is a neurodegenerative disease that causes anthropometric changes characterised by functional disability, increase in fat mass, and decrease in lean mass. All these variables are related to a greater cardiac risk. The polyphenol epigallocatechin gallate (EGCG) and an increase in ketone bodies in the blood have been shown to have beneficial effects on anthropometric and biochemical variables related to cardiovascular activity. The aim of this study was to analyse the impact of the intervention with EGCG and ketone bodies on cardiac risk in MS patients. A population of 51 MS patients were randomly assigned to a control group and an intervention group (daily dose of 800 mg of EGCG and 60 mL of coconut oil). Both groups followed an isocaloric diet for 4 months. Levels of beta-hydroxybutyrate (BHB), albumin, paraoxonase 1 (PON1) and C-reactive protein (CRP) were measured in serum before and after the intervention, as well as determining functional ability, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and muscle percentage. After 4 months, in the intervention group there was a significant increase in BHB, PON1 and albumin, while CRP did not vary; a significant decrease in cardiac risk associated with a significant decline in WHR; as well as a significant increase in muscle percentage. By contrast, these changes were not observed in the control group. Finally, results from analysis of variance (ANOVA) revealed a significant time-condition interaction effect, observing that WHtR and fat mass decreased in the intervention group, while they increased in the control group.
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Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial.
Quirós-Fernández, R, López-Plaza, B, Bermejo, LM, Palma-Milla, S, Gómez-Candela, C
Nutrients. 2019;(3)
Abstract
Hydroxytyrosol (HT) and Punicalagin (PC) exert cardioprotective and anti-atherosclerotic effects. This study evaluates the effect of oral supplementation with HT and PC (SAx) on early atherosclerosis markers in middle-aged, seemingly healthy adults. A randomized, double-blinded, placebo-controlled, crossover trial was performed for 20 weeks. There were two treatment sequences (Placebo/SAx, n = 41; SAx/Placebo, n = 43) for which the intervention periods (Placebo and SAx) were 8 weeks long, followed by a 4-week wash out period. The supplement was composed of 9.9 mg of HT and 195 mg of PC, and the placebo was composed of maltodextrin. SAx increased endothelial function (Flow-mediated dilatation [FMD]: 2.36%; p < 0.001) in the endothelial dysfunction subgroup compared to the placebo (2.36 ± 3.9 vs. 0.76 ± 3.5%, p < 0.05). SAx also reduced oxLDL by -28.74 ng/mL (p < 0.05) in subjects with higher levels of oxLDL, which was an improvement compared with the placebo (-28.74 ± 40.2 vs. 25.64 ± 93.8 ng/mL, p < 0.001). The prehypertension and hypertension subgroups exhibited decreased systolic (-15.75 ± 9.9 mmHg; p < 0.001) and diastolic (-6.36 ± 8.7 mmHg; p < 0.001) blood pressure after SAx consumption. Moreover, the systolic prehypertension and hypertension subgroups presented significant differences in systolic blood pressure compared to the placebo (-15.75 ± 9.9 vs. -2.67 ± 12.0 mmHg, p < 0.05). In conclusion, the supplement exerted anti-atherosclerotic effects by improving endothelial function, blood pressure, and levels of circulating oxLDL, especially for persons in whom these parameters were altered.
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The perioperative effect of magnesium sulfate in patients with concentric left ventricular hypertrophy undergoing cardiac surgery: A double-blinded randomized study.
Soliman, R, Abukhudair, W
Annals of cardiac anaesthesia. 2019;(3):246-253
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OBJECTIVE The objective of this study was to assess the cardioprotective effect of magnesium sulfate in patients with left ventricular concentric hypertrophy undergoing cardiac surgery. DESIGN The study was a double-blinded randomized study. SETTING This study was conducted at a cardiac center. PATIENTS The study included 250 patients. INTERVENTION The study included two groups (each = 125): Group M - the patients who received magnesium sulfate infusion (15 mg/kg/h). The infusion was started 20 min before induction, during surgery, and the first postoperative 24 h. Group C - the patients who received an equal amount of normal saline. MEASUREMENTS The variables included troponin I level, creatinine kinase-MB (CK-MB) level, electrocardiograph (ECG) with automatic ST-segment analysis (leads II and V), E/A peak ratio, end-diastolic volume, cardiac index (CI), heart rate, mean arterial blood pressure (MAP), mean arterial pulmonary pressure (mPAP), pulmonary and systemic vascular resistances, and pharmacological and mechanical support. MAIN RESULTS The troponin I level, CK-MB, and ECG changes were lower in Group M than Group C (P < 0.05). The E/A peak ratio and end-diastolic volume increased in Group M than Group C (P < 0.05). There was a significant increase in the CI and a decrease in the heart rate, mPAP, pulmonary vascular resistances, and pharmacological and mechanical support in Group M compared to Group C (P < 0.05). There were minimal changes in the MAP and systemic vascular resistance in Group M compared to Group C (P < 0.05). CONCLUSION The magnesium sulfate provides a cardioprotective effect in patients with concentric ventricular hypertrophy undergoing cardiac surgery. It decreases the incidence of perioperative myocardial infarction and arrhythmia. Furthermore, it decreases the requirement of pharmacological and mechanical support.
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Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial.
Kamenshchikov, NO, Mandel, IA, Podoksenov, YK, Svirko, YS, Lomivorotov, VV, Mikheev, SL, Kozlov, BN, Shipulin, VM, Nenakhova, AA, Anfinogenova, YJ
The Journal of thoracic and cardiovascular surgery. 2019;(6):2328-2336.e1
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OBJECTIVES The aim of this pilot study was to elucidate the effects of exogenous nitric oxide (NO) supply to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS A total of 60 patients with coronary artery disease scheduled for CABG with CPB were enrolled in a prospective randomized study. Patients were allocated randomly to receive treatment according to standard or modified CPB protocol where 40-ppm NO was added to the CPB circuit during cardiac surgery. The primary endpoint was the measurement of cardiac troponin I (cTnI). The secondary end points consisted in the measurements of creatine kinase-muscle/brain fraction (CK-MB) and vasoactive inotropic score (VIS). RESULTS NO delivered into the CPB circuit had a cardioprotective effect. The level of cTnI was significantly lower in NO-treated group compared with the control group 6 hours after surgery: 1.79 ± 0.39 ng/mL versus 2.41 ± 0.55 ng/mL, respectively (P = .001). The CK-MB value was significantly lower in NO-treated group compared with the control group 24 hours after surgery: 47.69 ± 8.08 U/L versus 62.25 ± 9.78 U/L, respectively (P = .001); and the VIS was significantly lower in the NO-treated group 6 hours after the intervention. CONCLUSIONS NO supply to the CPB circuit during CABG exerted a cardioprotective effect and was associated with lower levels of VIS and cardiospecific blood markers cTnI and CK-MB.
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Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center.
Nozari, Y, Eshraghi, A, Talasaz, AH, Bahremand, M, Salamzadeh, J, Salarifar, M, Pourhosseini, H, Jalali, A, Mortazavi, SH
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2018;(3):213-221
Abstract
BACKGROUND Evidence suggests that oxidative stress plays a principal role in myocardial damage following ischemia/reperfusion events. Recent studies have shown that the antioxidant properties of N-acetylcysteine (NAC) may have cardioprotective effects in high doses, but-to the best of our knowledge-few studies have assessed this. OBJECTIVES Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury. METHODS We conducted a randomized double-blind placebo-controlled trial in which 100 consecutive patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly assigned to the case group (high-dose NAC 100 mg/kg bolus followed by intracoronary NAC 480 mg during PCI then intravenous NAC 10 mg/kg for 12 h) or the control group (5% dextrose). We measured differences in peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction frame count (cTFC). RESULTS The peak CK-MB level was comparable between the two groups (P = 0.327), but patients receiving high-dose NAC demonstrated a significantly larger reduction in hs-TnT (P = 0.02). In total, 94% of the NAC group achieved TIMI flow grade 3 versus 80% of the control group (P = 0.03). No significant differences were observed between the two groups in terms of changes in the cTFC and MBG. CONCLUSIONS In this study, NAC improved myocardial reperfusion markers and coronary blood flow, as revealed by differences in peak hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large samples are warranted to elucidate the role of NAC in this population. ClinicalTrials.gov identifier: NCT01741207, and the Iranian Registry of Clinical Trials (IRCT; http://irct.ir ) registration number: IRCT201301048698N8.
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Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double-Blind Controlled Trial.
Lannemyr, L, Ricksten, SE, Rundqvist, B, Andersson, B, Bartfay, SE, Ljungman, C, Dahlberg, P, Bergh, N, Hjalmarsson, C, Gilljam, T, et al
Journal of the American Heart Association. 2018;(16):e008455
Abstract
Background The management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment. Methods and Results In a randomized double-blind study, we assigned patients with chronic heart failure (left ventricular ejection fraction <40%) and impaired renal function (glomerular filtration rate <80 mL/min per 1.73 m2) to receive either levosimendan (loading dose 12 μg/kg+0.1 μg/kg per minute) or dobutamine (7.5 μg/kg per minute) for 75 minutes. A pulmonary artery catheter was used for measurements of systemic hemodynamics, and a renal vein catheter was used to measure renal plasma flow by the infusion clearance technique for PAH (para-aminohippurate) corrected by renal extraction of PAH . Filtration fraction was measured by renal extraction of chromium ethylenediamine tetraacetic acid. A total of 32 patients completed the study. Following treatment, the levosimendan and dobutamine groups displayed similar increases in renal blood flow (22% and 26%, respectively) with no significant differences between groups. Glomerular filtration rate increased by 22% in the levosimendan group but remained unchanged in the dobutamine group ( P=0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine ( P=0.045). Conclusions In patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02133105.
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Prevention of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery: A Double-Blind Randomized Clinical Pilot Study Comparing Dobutamine and Milrinone.
Cavigelli-Brunner, A, Hug, MI, Dave, H, Baenziger, O, Buerki, C, Bettex, D, Cannizzaro, V, Balmer, C
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2018;(7):619-625
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OBJECTIVES Dobutamine and milrinone are commonly used after open-heart surgery to prevent or treat low cardiac output syndrome. We sought to compare efficacy and safety of these drugs in pediatric patients. DESIGN Prospective, single-center, double-blinded, randomized clinical pilot study. SETTING Tertiary-care university children's hospital postoperative pediatric cardiac ICU. PATIENTS After written consent, 50 consecutive patients (age, 0.2-14.2 yr; median, 1.2 yr) undergoing open-heart surgery for congenital malformations were included. INTERVENTIONS After cardiopulmonary bypass, a continuous infusion of either dobutamine or milrinone was administered for the first 36 postoperative hours. Maximum dose: dobutamine 6 µg/kg/min, milrinone 0.75 µg/kg/min. MEASUREMENTS AND MAIN RESULTS There were no significant differences in demographic data, complexity of surgery, and intraoperative characteristics between the two study groups (dobutamine vs milrinone). Efficacy was defined as need for additional vasoactive support, which did not differ between groups (dobutamine 61% vs milrinone 67%; p = 0.71). Sodium nitroprusside was used more often in the dobutamine group (42% vs 13%; p = 0.019). Systolic blood pressure showed a trend toward higher values in the dobutamine group, whereas both drugs increased heart rate early postoperatively. Echocardiography demonstrated a consistently good cardiac function in both groups. Central venous oxygen saturation, serum lactate levels, urine output, time to chest tube removal, length of mechanical ventilation, ICU, and hospital stay were similar in both groups. Both drugs were well tolerated, no serious adverse events occurred. CONCLUSIONS Dobutamine and milrinone are safe, well tolerated, and equally effective in prevention of low cardiac output syndrome after pediatric cardiac surgery. The hemodynamic response of the two drugs is comparable. In uncomplicated cases, a trend toward the more cost-saving dobutamine might be anticipated; however, milrinone demonstrated a trend toward higher efficacy in afterload reduction.