左西孟旦联合螺内酯对慢性心力衰竭患者血清炎症因子水平及心室重构的影响研究
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摘要
目的:研究左西孟旦联合螺内酯对慢性心力衰竭患者血清炎症因子水平及心室重构的影响。方法:选择2015年1月-2017年12月我院干部病房收治的88例慢性心力衰竭患者,将其随机分为两组。对照组单纯口服螺内酯,每次20 mg,每天1次;观察组联合采取左西孟旦治疗。观察和比较两组治疗前后的心功能指标(左心室舒张期末内径、6 min步行试验、左心室射血分数以及左心室收缩期末内径),血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6 (interleukin-6,IL-6)、高敏C-反应蛋白(high sensitivity C-reactive protein,hs-CRP)、N端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)水平的变化情况。结果:治疗后,观察组的有效率明显高于对照组(90.91%vs. 72.73%,P<0.05);两组治疗后左心室舒张期末内径、左心室收缩期末内径、血清hs-CRP、TNF-α、IL-6和NT-proBNP水平均较治疗前显著降低,而左心室射血分数及6 min步行试验均较治疗前明显增加(P<0.05),且观察组左心室舒张期末内径、左心室收缩期末内径、血清hs-CRP、TNF-α、IL-6和NT-proBNP水平明显低于对照组,左心室射血分数及6 min步行试验显著高于对照组(P<0.05)。结论:左西孟旦联合螺内酯治疗慢性心力衰竭患者可能显著提高其临床疗效,可能与其有效改善患者的心功能以及心室重构、减轻机体炎症反应有关。
Objective: To study the effect of levosimendan combined spironolactone on the serum inflammatory factors levels and ventricular remodeling in patients with chronic heart failure. Methods: 88 cases of patients with chronic heart failure who were treated in our hospital from January 2015 to December 2017 were selected and randomly divided into two groups. The control group was treated with spironolactone alone, while the observation group was treated with levosimendan. The cardiac function indexes(left ventricular end-diastolic diameter, 6-minute walking test, left ventricular ejection fraction and left ventricular end-systolic diameter), serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), high sensitivity C-reactive protein(hs-CRP) and N-terminal pro-brain natriuretic peptide(NT-proBNP) levels were observed and compared between the two groups before and after treatment. Results: After treatment, the effective rate of observation group was significantly higher than that of the control group(90.91% vs. 72.73%, P<0.05). After treatment,left ventricular end diastolic diameter, left ventricular end systolic diameter, serum hs-CRP, TNF-α, IL-6 and NT-proBNP levels were significantly lower than those before treatment, while the left ventricular ejection fraction and 6-minute walking test were significantly increased(P<0.05), and the left ventricular end diastolic diameter, left ventricular end systolic diameter, serum levels of hs-CRP, TNF-α,IL-6 and NT-proBNP were significantly lower than those in the control group. The left ventricular ejection fraction and 6-minute walking test were significantly higher than those in the control group(P<0.05). Conclusion: Levosimendan combined with spironolactone may significantly improve its clinical efficacy in the treatment of chronic heart failure, which may be related to the effective improvement of cardiac function, ventricular remodeling and alleviating inflammation.
Objective: To study the effect of levosimendan combined spironolactone on the serum inflammatory factors levels and ventricular remodeling in patients with chronic heart failure. Methods: 88 cases of patients with chronic heart failure who were treated in our hospital from January 2015 to December 2017 were selected and randomly divided into two groups. The control group was treated with spironolactone alone, while the observation group was treated with levosimendan. The cardiac function indexes(left ventricular end-diastolic diameter, 6-minute walking test, left ventricular ejection fraction and left ventricular end-systolic diameter), serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), high sensitivity C-reactive protein(hs-CRP) and N-terminal pro-brain natriuretic peptide(NT-proBNP) levels were observed and compared between the two groups before and after treatment. Results: After treatment, the effective rate of observation group was significantly higher than that of the control group(90.91% vs. 72.73%, P<0.05). After treatment,left ventricular end diastolic diameter, left ventricular end systolic diameter, serum hs-CRP, TNF-α, IL-6 and NT-proBNP levels were significantly lower than those before treatment, while the left ventricular ejection fraction and 6-minute walking test were significantly increased(P<0.05), and the left ventricular end diastolic diameter, left ventricular end systolic diameter, serum levels of hs-CRP, TNF-α,IL-6 and NT-proBNP were significantly lower than those in the control group. The left ventricular ejection fraction and 6-minute walking test were significantly higher than those in the control group(P<0.05). Conclusion: Levosimendan combined with spironolactone may significantly improve its clinical efficacy in the treatment of chronic heart failure, which may be related to the effective improvement of cardiac function, ventricular remodeling and alleviating inflammation.
引文
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[6]Mortensen L A,Thiesson H C,Tougaard B,et al.The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity:a multicenter randomized,double-blind,clinical trial(the SPIRENtrial)[J].Bmc Nephrology,2018,19(1):105
[7]Vakharia P,Lund E,Rangel S,et al.LB953 Spironolactone and psoriasis outcome in young adult women:A report from the RADAR(Research on Adverse Drug events And Reports)project[J].Journal of Investigative Dermatology,2017,137(10):B4
[8]Jia L,Yin Q,Zhou L,et al.Insights into the mechanism of concomitant nucleation of form II and ethanol solvate of spironolactone in cooling crystallization[J].Rsc Advances,2018,8(18):9697-9706
[9]Vecchis R D,Noutsias M,Ariano C,et al.Does Accidental Overcorrection of Symptomatic Hyponatremia in Chronic Heart Failure Require Specific Therapeutic Adjustments for Preventing Central Pontine Myelinolysis?[J].Journal of Clinical Medicine Research,2017,9(4):266-272
[10]Pieske B,Maggioni A P,Csp L,et al.Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction:results of the SOluble guanylate Cyclase stimulatoR in heArT failurEpatientS with PRESERVED EF(SOCRATES-PRESERVED)study[J].European Heart Journal,2017,38(15):1119
[11]Ibrahim N E,Gaggin H K,Rabideau D J,et al.Worsening Renal Function during Management for Chronic Heart Failure with Reduced Ejection Fraction:Results From the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy(PROTECT)Study[J].Journal of Cardiac Failure,2017,23(2):121-130
[12]Mujtaba A,Taher M A,Hazza M A,et al.The Effect of Spironolactone on the Incidence of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Catheterization:Study Design and Rationale[J].Cardiology&Therapy,2018,7(1):101-106
[13]Azmy B,Standen G,Kristova P,et al.Nanostructured DPA-MPC-DPA triblock copolymer gel for controlled drug release of ketoprofen and spironolactone[J].Journal of Pharmacy&Pharmacology,2017,69(8):978-990
[14]Chen Y,Liu P,Chen X,et al.Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy[J].American Journal of the Medical Sciences,2018,355(5):418-424
[15]Kandasamy A,Simon H A,Murthy P,et al.Comparison of Levosimendan versus Dobutamine in Patients with Moderate to Severe Left Ventricular Dysfunction Undergoing Off-pump Coronary Artery Bypass Grafting:A Randomized Prospective Study[J].Annals of Cardiac Anaesthesia,2017,20(2):200-206
[16]Cholley B,Caruba T,Grosjean S,et al.Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass:The LICORN Randomized Clinical Trial[J].Jama,2017,318(6):548
[17]Rafoulistergiou P,Parissis J T,Farmakis D,et al.Effects of levosimendan on markers of kidney function in patients with acutely decompensated heart failure and renal impairment[J].Journal of Cardiovascular Medicine,2017,18(10):771-773
[18]Hansen M S,Andersen A,Tolbod L P,et al.Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure[J].Pulmonary Circulation,2018,8(1):2045893217743122.
[19]Desai P M,Sarkar M S,Umbarkar S R.Prophylactic Preoperative Levosimendan for off-Pump Coronary Artery Bypass Grafting in Patients with Left Ventricular Dysfunction:Single-centered Randomized Prospective Study[J].Annals of Cardiac Anaesthesia,2018,21(2):123-128
[20]Udayasankar S.Question 2 Is levosimendan better than milrinone in preventing post operative low cardiac output syndrome and improving cardiac function in children with congenital heart disease[J].Archives of Disease in Childhood,2017,102(6):590
[21]Sahu M K,Gupta A,Alam I,et al.Modified Blalock-Taussig Shunt and Levosimendan for Left Ventricular Preparation in a Child with Transposition of Great Arteries and Regressed Ventricle Undergoing Rapid 2 Stage Arterial Switch Operation[J].Annals of Cardiac Anaesthesia,2017,20(2):265-267
[22]Sanfilippo F,Knight J B,Scolletta S,et al.Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery:a systematic review and meta-analysis[J].Critical Care,2017,21(1):252
[23]Babaev M A,Eremenko A A,Dymova O V,et al.Levosimendan in preoperation therapy for cardiosurgery in patients with chronic heart failure[J].Russian Journal of Cardiology,2017,143(3):59-62
[24]Yang B,Wang F,Cao H,et al.Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells[J].Experimental&Therapeutic Medicine,2017,14(5):4224-4230
[25]Sukoyan G V,Ionov D I,Galenko-Iaroshevsky P A,et al.Severity of Symptoms of Systemic Inflammatory Response Syndrome and Congestive Heart Failure Caused by Chronic Aortic Stenosis and Its Pharmacological Correction[J].World Journal of Cardiovascular Diseases,2017,07(12):465-476
[26]Sharma A,Stevens S R,Lucas J,et al.Utility of Growth Differentiation Factor-15,A Marker of Oxidative Stress and Inflammation,in Chronic Heart Failure:Insights From the HF-ACTION Study[J].Jacc Heart Fail,2017,5(10):724-734
[27]Grande D,Leone M,Rizzo C,et al.A Multiparametric Approach Based on NT-proBNP,ST2,and Galectin3 for Stratifying One Year Prognosis of Chronic Heart Failure Outpatients[J].Journal of Cardiovascular Development&Disease,2017,4(3):0009
[28]Bobbio E,Isgaard J,Swedberg K,et al.NT-proBNP Levels Are Reduced Following Treatment With Growth Hormone in Chronic Heart Failure Due to Ischemic Heart Disease.A Randomized Double Blind Placebo Controlled Trial[J].Journal of Heart&Lung Transplantation,2018,37(4):S187-S188
[29]Davarzani N,Sandersvan W S,Karel J,et al.N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations-Results From TIME-CHF[J].Journal of Cardiac Failure,2017,23(5):382
[30]Stienen S,Salah K,Moons A H,et al.NT-proBNP-Guided Therapy in Acute Decompensated Heart Failure:The PRIMA II Randomized Controlled Trial[J].Circulation,2017,23(5):811-821
[2]Saitoh M,Dos Santos M R,Emami A,et al.Anorexia,functional capacity,and clinical outcome in patients with chronic heart failure:results from the Studies Investigating Co-morbidities Aggravating Heart Failure(SICA‐HF)[J].Esc Heart Failure,2017,4(4):448-457
[3]Dos Santos M R,Saitoh M,Ebner N,et al.Sarcopenia and Endothelial Function in Patients With Chronic Heart Failure:Results From the Studies Investigating Comorbidities Aggravating Heart Failure(SICA-HF)[J].Journal of the American Medical Directors Association,2017,18(3):240-245
[4]Yohannes A M,Chen W,Moga A M,et al.Cognitive Impairment in Chronic Obstructive Pulmonary Disease and Chronic Heart Failure:ASystematic Review and Meta-analysis of Observational Studies[J].Journal of the American Medical Directors Association,2017,18(5):451.e1-451.e11
[5]van Veldhuisen D J,Ponikowski P,Van d M P,et al.Effect of Ferric Carboxymaltose on Exercise Capacity in Patients with Chronic Heart Failure and Iron Deficiency[J].Circulation,2017,136(15):1374-1383
[6]Mortensen L A,Thiesson H C,Tougaard B,et al.The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity:a multicenter randomized,double-blind,clinical trial(the SPIRENtrial)[J].Bmc Nephrology,2018,19(1):105
[7]Vakharia P,Lund E,Rangel S,et al.LB953 Spironolactone and psoriasis outcome in young adult women:A report from the RADAR(Research on Adverse Drug events And Reports)project[J].Journal of Investigative Dermatology,2017,137(10):B4
[8]Jia L,Yin Q,Zhou L,et al.Insights into the mechanism of concomitant nucleation of form II and ethanol solvate of spironolactone in cooling crystallization[J].Rsc Advances,2018,8(18):9697-9706
[9]Vecchis R D,Noutsias M,Ariano C,et al.Does Accidental Overcorrection of Symptomatic Hyponatremia in Chronic Heart Failure Require Specific Therapeutic Adjustments for Preventing Central Pontine Myelinolysis?[J].Journal of Clinical Medicine Research,2017,9(4):266-272
[10]Pieske B,Maggioni A P,Csp L,et al.Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction:results of the SOluble guanylate Cyclase stimulatoR in heArT failurEpatientS with PRESERVED EF(SOCRATES-PRESERVED)study[J].European Heart Journal,2017,38(15):1119
[11]Ibrahim N E,Gaggin H K,Rabideau D J,et al.Worsening Renal Function during Management for Chronic Heart Failure with Reduced Ejection Fraction:Results From the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy(PROTECT)Study[J].Journal of Cardiac Failure,2017,23(2):121-130
[12]Mujtaba A,Taher M A,Hazza M A,et al.The Effect of Spironolactone on the Incidence of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Catheterization:Study Design and Rationale[J].Cardiology&Therapy,2018,7(1):101-106
[13]Azmy B,Standen G,Kristova P,et al.Nanostructured DPA-MPC-DPA triblock copolymer gel for controlled drug release of ketoprofen and spironolactone[J].Journal of Pharmacy&Pharmacology,2017,69(8):978-990
[14]Chen Y,Liu P,Chen X,et al.Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy[J].American Journal of the Medical Sciences,2018,355(5):418-424
[15]Kandasamy A,Simon H A,Murthy P,et al.Comparison of Levosimendan versus Dobutamine in Patients with Moderate to Severe Left Ventricular Dysfunction Undergoing Off-pump Coronary Artery Bypass Grafting:A Randomized Prospective Study[J].Annals of Cardiac Anaesthesia,2017,20(2):200-206
[16]Cholley B,Caruba T,Grosjean S,et al.Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass:The LICORN Randomized Clinical Trial[J].Jama,2017,318(6):548
[17]Rafoulistergiou P,Parissis J T,Farmakis D,et al.Effects of levosimendan on markers of kidney function in patients with acutely decompensated heart failure and renal impairment[J].Journal of Cardiovascular Medicine,2017,18(10):771-773
[18]Hansen M S,Andersen A,Tolbod L P,et al.Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure[J].Pulmonary Circulation,2018,8(1):2045893217743122.
[19]Desai P M,Sarkar M S,Umbarkar S R.Prophylactic Preoperative Levosimendan for off-Pump Coronary Artery Bypass Grafting in Patients with Left Ventricular Dysfunction:Single-centered Randomized Prospective Study[J].Annals of Cardiac Anaesthesia,2018,21(2):123-128
[20]Udayasankar S.Question 2 Is levosimendan better than milrinone in preventing post operative low cardiac output syndrome and improving cardiac function in children with congenital heart disease[J].Archives of Disease in Childhood,2017,102(6):590
[21]Sahu M K,Gupta A,Alam I,et al.Modified Blalock-Taussig Shunt and Levosimendan for Left Ventricular Preparation in a Child with Transposition of Great Arteries and Regressed Ventricle Undergoing Rapid 2 Stage Arterial Switch Operation[J].Annals of Cardiac Anaesthesia,2017,20(2):265-267
[22]Sanfilippo F,Knight J B,Scolletta S,et al.Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery:a systematic review and meta-analysis[J].Critical Care,2017,21(1):252
[23]Babaev M A,Eremenko A A,Dymova O V,et al.Levosimendan in preoperation therapy for cardiosurgery in patients with chronic heart failure[J].Russian Journal of Cardiology,2017,143(3):59-62
[24]Yang B,Wang F,Cao H,et al.Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells[J].Experimental&Therapeutic Medicine,2017,14(5):4224-4230
[25]Sukoyan G V,Ionov D I,Galenko-Iaroshevsky P A,et al.Severity of Symptoms of Systemic Inflammatory Response Syndrome and Congestive Heart Failure Caused by Chronic Aortic Stenosis and Its Pharmacological Correction[J].World Journal of Cardiovascular Diseases,2017,07(12):465-476
[26]Sharma A,Stevens S R,Lucas J,et al.Utility of Growth Differentiation Factor-15,A Marker of Oxidative Stress and Inflammation,in Chronic Heart Failure:Insights From the HF-ACTION Study[J].Jacc Heart Fail,2017,5(10):724-734
[27]Grande D,Leone M,Rizzo C,et al.A Multiparametric Approach Based on NT-proBNP,ST2,and Galectin3 for Stratifying One Year Prognosis of Chronic Heart Failure Outpatients[J].Journal of Cardiovascular Development&Disease,2017,4(3):0009
[28]Bobbio E,Isgaard J,Swedberg K,et al.NT-proBNP Levels Are Reduced Following Treatment With Growth Hormone in Chronic Heart Failure Due to Ischemic Heart Disease.A Randomized Double Blind Placebo Controlled Trial[J].Journal of Heart&Lung Transplantation,2018,37(4):S187-S188
[29]Davarzani N,Sandersvan W S,Karel J,et al.N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations-Results From TIME-CHF[J].Journal of Cardiac Failure,2017,23(5):382
[30]Stienen S,Salah K,Moons A H,et al.NT-proBNP-Guided Therapy in Acute Decompensated Heart Failure:The PRIMA II Randomized Controlled Trial[J].Circulation,2017,23(5):811-821