射血分数保留的心力衰竭治疗进展
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摘要
射血分数保留的心力衰竭(HFpEF)是一组常见的临床症候群。随着发病率增加,HFpEF逐渐引起了人们的关注,但目前仍无指南推荐标准治疗方案。近年来在HFpEF治疗领域取得一些新的进展,新型药物及相关器械治疗逐渐成为研究热点。
Heart failure with preserved ejection fraction(HFpEF) is a common clinical syndrome. With the increase of incidence,HFpEF has attracted more and more attention,but there is still no guideline to recommend standard treatment. In recent years,some new advances have been made in the field of HFpEF treatment. New drugs and related devices have gradually been a research hotspot.
Heart failure with preserved ejection fraction(HFpEF) is a common clinical syndrome. With the increase of incidence,HFpEF has attracted more and more attention,but there is still no guideline to recommend standard treatment. In recent years,some new advances have been made in the field of HFpEF treatment. New drugs and related devices have gradually been a research hotspot.
引文
[1] Ponikowski P,Voors AA,Anker SD,et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure:The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology(ESC). Developed with the special contribution of the Heart Failure Association(HFA)of the ESC[J]. Eur J Heart Fail,2016,18(8),891-975.
[2] Bouchi R,Terashima M,Sasahara Y,et al.Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes:a pilot study[J]. Cardiovasc Diabetol,2017,16(1):32.
[3] Paulus WJ,Tschpe C. A novel paradigm for heart failure with preserved ejection fraction[J]. J Am Coll Cardiol,2013,62(4):263-271.
[4] Kai H,Kuwahara F,Tokuda K,et al.Diastolic dysfunction in hypertensive hearts:roles of perivascular inflammation and reactive myocardial fibrosis[J]. Hypertens Res,2005,28(6):483.
[5] Kuwahara F,Kai H,Tokuda K,et al.Hypertensive myocardial fibrosis and diastolic dysfunction:another model of inflammation?[J]. Hypertension,2004,43(4):739-745.
[6] Savoia C,Schiffrin EL. Vascular inflammation in hypertension and diabetes:molecular mechanisms and therapeutic interventions[J]. Clin Sci(Lond),2007,112(7):375-384.
[7] Glezeva N,Baugh JA. Role of inflammation in the pathogenesis of heart failure with preserved ejection fraction and its potential as a therapeutic target[J].Heart Fail Rev,2014,19(5):681-694.
[8] Pieske B,Maggioni AP,Lam CS,et al.Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction:results of the SOluble guanylate Cyclase stimulatoR in he Ar T failur E patient S with PRESERVED EF(SOCRATES-PRESERVED)study[J]. Eur Heart J,2017,38(15):1119.
[9] Gorter TM,Hoendermis ES,van Veldhuisen DJ,et al.Right ventricular dysfunction in heart failure with preserved ejection fraction:a systematic review and meta-analysis[J]. Eur J Heart Fail,2016,18(12):1472-1487.
[10] Lam CS,Roger VL,Rodeheffer RJ,et al.Pulmonary hypertension in heart failure with preserved ejection fraction:a community-based study[J]. J Am Coll Cardiol,2009,53(13):1119-1126.
[11] Rosenkranz S,Gibbs J S,Wachter R,et al.Left ventricular heart failure and pulmonary hypertension[J]. Eur Heart J,2016,37(12):942-954.
[12] Fayyaz AU,Edwards WD,Maleszewski JJ,et al.Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction[J]. Circulation,2018,137(17):1796-1810.
[13] Guazzi M,Vicenzi M,Arena R,et al. Pulmonary hypertension in heart failure with preserved ejection fraction:a target of phosphodiesterase-5 inhibition in a 1-year study[J]. Circulation,2011,124(2):164-174.
[14] Opitz CF,Hoeper MM,Gibbs JS,et al.Pre-capillary,combined,and post-capillary pulmonary hypertension:a pathophysiological continuum[J]. J Am Coll Cardiol,2016,68(4):368-378.
[15] Redfield MM,Chen HH,Borlaug BA,et al.Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction:a randomized clinical trial[J]. JAMA,2013,309(12):1268-1277.
[16] Liu LC,Hummel YM,van der Meer P,et al.Effects of sildenafil on cardiac structure and function,cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension[J]. Eur J Heart Fail,2017,19(1):116-125.
[17] Lachance D,Dhahri W,Drolet MC,et al.Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload[J]. BMC Cardiovasc Disord,2014,14(1):190.
[18] Steggall A,Mordi IR,Lang CC. Targeting metabolic modulation and mitochondrial dysfunction in the treatment of heart failure[J]. Diseases,2017,5(2). pii:E14.
[19] Maeder MT,Khammy O,dos Remedios C,et al.Myocardial and systemic iron depletion in heart failure[J]. J Am Coll Cardiol,2011,58(5):474-480.
[20] Voors AA,Düngen HD,Senni M,et al.Safety and tolerability of neladenoson bialanate,a novel oral partial adenosine A1 receptor agonist,in patients with chronic heart failure[J]. J Clin Pharmacol,2017,57(4):440-451.
[21] Holubarsch CJ,Rohrbach M,Karrasch M,et al.A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure:the ERGO(etomoxir for the recovery of glucose oxidation)study[J]. Clin Sci(Lond),2007,113(4):205-212.
[22] Fragasso G,Palloshi A,Puccetti P,et al.A randomized clinical trial of trimetazidine,a partial free fatty acid oxidation inhibitor,in patients with heart failure[J]. J Am Coll Cardiol,2006,48(5):992-998.
[23] Gao D,Ning N,Niu X,et al.Trimetazidine:a meta-analysis of randomised controlled trials in heart failure[J]. Heart,2010,97(4):278-286.
[24] van Heerebeek L,Franssen CPM,Hamdani N,et al.Molecular and cellular basis for diastolic dysfunction[J]. Curr Heart Fail Rep,2012,9(4):293-302.
[25] Kakkar R,Lee RT.Intramyocardial fibroblast myocyte communication[J]. Circ Res,2010,106(1):47.
[26] Chung CS,Granzier HL. Contribution of titin and extracellular matrix to passive pressure and measurement of sarcomere length in the mouse left ventricle[J]. J Mol Cell Cardiol,2011,50(4):731-739.
[27] Krüger M,Ktter S,Grützner A,et al.Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs[J]. BMC Pharmacol,2009,96(3):372a.
[28] Takimoto E,Champion HC,Li M,et al.Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy[J]. Nat Med,2005,11(2):214-222..
[29] Bishu K,Hamdani N,Mohammed SF,et al.Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo[J].Circulation,2011,124(25):2882-2891.
[30] van Heerebeek L,Hamdani N,Falcao-Pires I,et al. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction[J]. Circulation,2012,126(7):830-839.
[31] Lee DI,Zhu G,Sasaki T,et al.Phosphodiesterase 9A controls nitric-oxide-independent c GMP and hypertrophic heart disease[J]. Nature,2015,519(7544):472-476.
[32] Creemers EE,Pinto YM. Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart[J]. Cardiovasc Res,2010,89(2):265-272.
[33] Yamagami K,Oka T,Wang Q,et al.Pirfenidone exhibits cardioprotective effects by regulating myocardial fibrosis and vascular permeability in pressure-overloaded hearts[J]. Am J Physiol Heart Circ Physiol,2015,309(3):H512-H522.
[34] Miric G,Dallemagne C,Endre Z,et al.Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin‐diabetic rats[J]. Br J Pharmacol,2001,133(5):687.
[35] Lee KW,Everett TH,Rahmutula D,et al.Pirfenidone prevents the development of a vulnerable substrate for atrial fibrillation in a canine model of heart failure[J]. Circulation,2006,114(16):1703-1712.
[36] de Boer RA,Edelmann F,Cohen-Solal A,et al.Galectin-3 in heart failure with preserved ejection fraction[J]. Eur J Heart Fail,2013,15(10):1095-1101.
[37] Suthahar N,Meijers WC,SilljéHHW,et al.Galectin-3 activation and inhibition in heart failure and cardiovascular disease:an update[J]. Theranostics,2018,8(3):593-609.
[2] Bouchi R,Terashima M,Sasahara Y,et al.Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes:a pilot study[J]. Cardiovasc Diabetol,2017,16(1):32.
[3] Paulus WJ,Tschpe C. A novel paradigm for heart failure with preserved ejection fraction[J]. J Am Coll Cardiol,2013,62(4):263-271.
[4] Kai H,Kuwahara F,Tokuda K,et al.Diastolic dysfunction in hypertensive hearts:roles of perivascular inflammation and reactive myocardial fibrosis[J]. Hypertens Res,2005,28(6):483.
[5] Kuwahara F,Kai H,Tokuda K,et al.Hypertensive myocardial fibrosis and diastolic dysfunction:another model of inflammation?[J]. Hypertension,2004,43(4):739-745.
[6] Savoia C,Schiffrin EL. Vascular inflammation in hypertension and diabetes:molecular mechanisms and therapeutic interventions[J]. Clin Sci(Lond),2007,112(7):375-384.
[7] Glezeva N,Baugh JA. Role of inflammation in the pathogenesis of heart failure with preserved ejection fraction and its potential as a therapeutic target[J].Heart Fail Rev,2014,19(5):681-694.
[8] Pieske B,Maggioni AP,Lam CS,et al.Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction:results of the SOluble guanylate Cyclase stimulatoR in he Ar T failur E patient S with PRESERVED EF(SOCRATES-PRESERVED)study[J]. Eur Heart J,2017,38(15):1119.
[9] Gorter TM,Hoendermis ES,van Veldhuisen DJ,et al.Right ventricular dysfunction in heart failure with preserved ejection fraction:a systematic review and meta-analysis[J]. Eur J Heart Fail,2016,18(12):1472-1487.
[10] Lam CS,Roger VL,Rodeheffer RJ,et al.Pulmonary hypertension in heart failure with preserved ejection fraction:a community-based study[J]. J Am Coll Cardiol,2009,53(13):1119-1126.
[11] Rosenkranz S,Gibbs J S,Wachter R,et al.Left ventricular heart failure and pulmonary hypertension[J]. Eur Heart J,2016,37(12):942-954.
[12] Fayyaz AU,Edwards WD,Maleszewski JJ,et al.Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction[J]. Circulation,2018,137(17):1796-1810.
[13] Guazzi M,Vicenzi M,Arena R,et al. Pulmonary hypertension in heart failure with preserved ejection fraction:a target of phosphodiesterase-5 inhibition in a 1-year study[J]. Circulation,2011,124(2):164-174.
[14] Opitz CF,Hoeper MM,Gibbs JS,et al.Pre-capillary,combined,and post-capillary pulmonary hypertension:a pathophysiological continuum[J]. J Am Coll Cardiol,2016,68(4):368-378.
[15] Redfield MM,Chen HH,Borlaug BA,et al.Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction:a randomized clinical trial[J]. JAMA,2013,309(12):1268-1277.
[16] Liu LC,Hummel YM,van der Meer P,et al.Effects of sildenafil on cardiac structure and function,cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension[J]. Eur J Heart Fail,2017,19(1):116-125.
[17] Lachance D,Dhahri W,Drolet MC,et al.Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload[J]. BMC Cardiovasc Disord,2014,14(1):190.
[18] Steggall A,Mordi IR,Lang CC. Targeting metabolic modulation and mitochondrial dysfunction in the treatment of heart failure[J]. Diseases,2017,5(2). pii:E14.
[19] Maeder MT,Khammy O,dos Remedios C,et al.Myocardial and systemic iron depletion in heart failure[J]. J Am Coll Cardiol,2011,58(5):474-480.
[20] Voors AA,Düngen HD,Senni M,et al.Safety and tolerability of neladenoson bialanate,a novel oral partial adenosine A1 receptor agonist,in patients with chronic heart failure[J]. J Clin Pharmacol,2017,57(4):440-451.
[21] Holubarsch CJ,Rohrbach M,Karrasch M,et al.A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure:the ERGO(etomoxir for the recovery of glucose oxidation)study[J]. Clin Sci(Lond),2007,113(4):205-212.
[22] Fragasso G,Palloshi A,Puccetti P,et al.A randomized clinical trial of trimetazidine,a partial free fatty acid oxidation inhibitor,in patients with heart failure[J]. J Am Coll Cardiol,2006,48(5):992-998.
[23] Gao D,Ning N,Niu X,et al.Trimetazidine:a meta-analysis of randomised controlled trials in heart failure[J]. Heart,2010,97(4):278-286.
[24] van Heerebeek L,Franssen CPM,Hamdani N,et al.Molecular and cellular basis for diastolic dysfunction[J]. Curr Heart Fail Rep,2012,9(4):293-302.
[25] Kakkar R,Lee RT.Intramyocardial fibroblast myocyte communication[J]. Circ Res,2010,106(1):47.
[26] Chung CS,Granzier HL. Contribution of titin and extracellular matrix to passive pressure and measurement of sarcomere length in the mouse left ventricle[J]. J Mol Cell Cardiol,2011,50(4):731-739.
[27] Krüger M,Ktter S,Grützner A,et al.Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs[J]. BMC Pharmacol,2009,96(3):372a.
[28] Takimoto E,Champion HC,Li M,et al.Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy[J]. Nat Med,2005,11(2):214-222..
[29] Bishu K,Hamdani N,Mohammed SF,et al.Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo[J].Circulation,2011,124(25):2882-2891.
[30] van Heerebeek L,Hamdani N,Falcao-Pires I,et al. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction[J]. Circulation,2012,126(7):830-839.
[31] Lee DI,Zhu G,Sasaki T,et al.Phosphodiesterase 9A controls nitric-oxide-independent c GMP and hypertrophic heart disease[J]. Nature,2015,519(7544):472-476.
[32] Creemers EE,Pinto YM. Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart[J]. Cardiovasc Res,2010,89(2):265-272.
[33] Yamagami K,Oka T,Wang Q,et al.Pirfenidone exhibits cardioprotective effects by regulating myocardial fibrosis and vascular permeability in pressure-overloaded hearts[J]. Am J Physiol Heart Circ Physiol,2015,309(3):H512-H522.
[34] Miric G,Dallemagne C,Endre Z,et al.Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin‐diabetic rats[J]. Br J Pharmacol,2001,133(5):687.
[35] Lee KW,Everett TH,Rahmutula D,et al.Pirfenidone prevents the development of a vulnerable substrate for atrial fibrillation in a canine model of heart failure[J]. Circulation,2006,114(16):1703-1712.
[36] de Boer RA,Edelmann F,Cohen-Solal A,et al.Galectin-3 in heart failure with preserved ejection fraction[J]. Eur J Heart Fail,2013,15(10):1095-1101.
[37] Suthahar N,Meijers WC,SilljéHHW,et al.Galectin-3 activation and inhibition in heart failure and cardiovascular disease:an update[J]. Theranostics,2018,8(3):593-609.