Impaired Left Atrial Reservoir Function in Metabolic Syndrome Predicts Symptoms in HFpEF Patients


  • Gëzim Berisha
  • Gani Bajraktari Clinic of Cardiology, University Clinical Centre of Kosova, Pishtina, Republic of Kosovo Medical Faculty, University of Prishtina “Hasan Prishtina”, Pishtina, Republic of Kosovo
  • Pranvera Ibrahimi
  • Ibadete Bytyçi
  • Nehat Rexhepaj
  • Shpend Elezi
  • Michael Y Henein



Background and Aim. The Metabolic Syndrome (MetS) has been shown to be independently associated with increased risk for incident heart failure (HF) and coronary artery disease. The aim of this study was to investigate the additional effect of MetS on LA dysfunction in a group of patients with HF and preserved ejection fraction (HFpEF) and its relationship with symptoms.

Methods. This study included 194 consecutive patients (age 62 ± 9 years) with stable HFpEF. LV dimensions, ejection fraction (EF), mitral annulus peak systolic excursion (MAPSE), myocardial velocities (s’, e’ and a’), LA dimensions and volumes were measured. Total LA emptying fraction (LA EF) was measured by Simpson rule volumes. Based on the NCEP-ATP III criteria, patients were divided into two groups; MetS (n=95) and non-MetS (n=108) and were compared with 34 age and gender matched controls.

Results. Age and gender were not different between patients and control neither between MetS and non-Met. LV dimensions, EF and longitudinal function indices were also not different. The MetS patients had higher LV mass index (p=0.038), lower septal and lateral e’ (p=0.003 and p=0.001, respectively) velocities, larger LA minimal volume (p=0.007) and lower LA EF (p<0.001) compared with the non-MetS patients. Age, LA EF and MetS independently predicted the NYHA class.

Conclusions. Despite no difference in LV systolic function, patients with HFpEF and MetS have worse LA emptying fraction, compared with HFpEF and non-MetS patients. In addition, LA reservoir function impairment and MetS independently predict patients limiting symptoms, thus add to a better understanding of HFpEF.


Boulogne A, Vantyghem MC. Epidemiological data and screening criteria of the metabolic syndrome. Presse Med 2004; 33: 662-5. doi: 10.1016/S0755-4982(04)98711-8.

Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683-9. doi: 10.2337/diacare.24.4.683.

Ivanovica BA, Tadic MV, Simic DV. Predictors of global left ventricular function in metabolic syndrome. Arq Bras Cardiol 2001; 96: 377-84. doi: 10.1590/S0066-782X2011005000039.

Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288: 2709-16. doi: 10.1001/jama.288.21.2709.

McCullough AJ. Epidemiology of the metabolic syndrome in the USA. J Dig Dis 2011; 12: 333-40. doi: 10.1111/j.1751-2980.2010.00469.x.

Meiqs JB. Epidemiology of the metabolic syndrome. AM J Manag Care 2002; 8: 283-92.

Ferrara LA, Giuda L, Ferrera F, De Luca G, Staiano L, Calentano A, Mancini M. Cardiac structure and function and arterial circulation in hypertensive patients with and without metabolic syndrome. J Hum Hypertens 2007; 21: 729-35. doi: 10.1038/sj.jhh.1002222.

de las Fuentes L, Brown AL, Mathews SJ, Waggoner AD, Soto PF, Gropler RJ, et al. Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass. Eur Heart J 2007; 28: 553-559. doi: 10.1093/eurheartj/ehl526.

Penjasković D, Sakac D, Dejanović J, Zec R, Zec Petković N, Stojsić Milosavljević A. Left ventricular diastolic dysfunction in patients with metabolic syndrome. Med Pregl 2012; 65: 18-22.

Masugata H, Senda S, Goda F, Yoshihara Y, Yoshikawa K, Fujita N, et al. Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome. Hypertens Res 2006; 29: 897-903. doi:10.1291/hypres.29.897.

Fiuza, M. Metabolic syndrome and coronary artery disease. Rev Port Cardiol 2012; 3: 779-82.

Malik S, Wong ND, Franklin SS, Kamath TV, L’italien GJ, Pio JR, et al. Impact of the Metabolic Syndrome on Mortality From Coronary Heart Disease, Cardiovascular Disease, and all Causes in United States Adults. Circulation 2004; 110: 1245-50. doi: 10.1161/01.CIR.0000140677.20606.0E.

Li SH, Yang B, Gong HP, Tan HW, Zhong M, Zhang Y, et al. Impaired atrial synchronicity in patients with metabolic syndrome associated with insulin resistance and independent of hypertension. Hypertens Res 2009; 32: 791-61. doi: 10.1038/hr.2009.105.

Crendel E, Walther G, Dutheil F, Courteix D, Lesourd B, Chapier R, et al. Left ventricular myocardial dyssynchrony is already present in nondiabetic patients with metabolic syndrome. Can J Cardiol 2014; 30: 320-4. doi: 10.1016/j.cjca.2013.10.019.

Kurt M, Tanboğa IH, Büyükkaya E, Karakaş MF, Akçay AB, Sen N, et al. Relation of presence and severity of metabolic syndrome with left atrial mechanics in patients without overt diabetes: a deformation imaging study. Anadolu Kardiyol Derg 2014; 14: 128-33. doi: 10.5152/akd.2014.4686.

Yilmaz M, Ozlem AO, Akgumus A, Peker T, Karaagac K, Vatansever F, et al. Left atrial mechanical functions in patients with the metabolic syndrome. Acta Cardiol 2013; 68: 133-7.

Kurt M, Wang J, Torre-Amione G, Nagusha SG. Left atrial function in diastolic heart failure. Circ Cardiovasc Imaging 2009; 2: 10-5. doi: 10.1161/CIRCIMAGING.108.813071.

Teo SG, Yang H, Chai P, Yeo TC. Impact of left ventricular diastolic dysfunction on left atrial volume and function: a volumetric analysis. Eur J echocardiogr 2010; 11: 38-43. doi: 10.1093/ejechocard/jep153.

Tsang TS, Barnes ME, Gersh BJ, Bailet KR, Sewerd JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am J Cardiol 2002; 90: 1284-9. doi: 10.1016/S0002-9149(02)02864-3.

Chinali M, de Simone G, Roman MJ, Bella JN, Liu JE, Lee ET, et al. Left atrial systolic force and cardiovascular outcome. The Strong Heart Study. Am J Hypertens 2005; 18: 1570-6. doi: 10.1016/j.amjhyper.2005.05.036.

Koprowski P, Kostkiewicz M, Leśniak-Sobelga A. Echocardiographic assessment of left atrial volume in asymptomatic ambulatory patients with metabolic syndrome and/or arterial hypertension - is it parameter worth into considerate? Przegl Lek 2012; 69: 1199- 204.

Maeder MT, Rickli H. Heart failure with preserved left ventricular ejection fraction. Praxis (Bern 2014) 2013; 102: 1299-307. doi: 10.1024/1661-8157/a001439.

Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: Pathophysiology, diagnosis, and treatman. Eur Heart J 2011; 32: 670-9. doi: 10.1093/eurheartj/ehq426.

Guan Z, Zhang D, Huang R, Zhang F, Wang Q, Guo S. Association of left atrial myocardial function with left ventricular diastolic dysfunction in subjects with preserved systolic function: a strain rate imaging study. Clin Cardiol 2010; 33: 643-9. doi: 10.1002/clc.20784.

Bilen E, Kurt M, Tanboĝa IH, Kocak U, Ayhan H, Durmaz T, et al. Assessment of left atrial phasic functions in heart failure patients with preserved or low ejection fraction. Turk Kardiyol Dern Ars 2012; 40: 122-8. doi: 10.5543/tkda.2012.01802.

Grundy SM, Breweber HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, American Heart Association; National Heart, Lung and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung and Blood Institute/ American Heart Association conference on scientific issues related to definition. Circulation 2004; 109: 433-8. doi: 10.1161/01.CIR.0000111245.75752.C6

Höglund C, Alam M, Thorstrand C. Atrioventricular valve plane displacement in healthypersons. An echocardiographic study. Acta Med Scand 1988; 224: 557-62.

Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to leftventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988; 12: 426-40. doi: 10.1016/0735-1097(88)90416-0

Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, et al; American Society of Echocardiography. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003; 16: 777-802. doi: 10.1016/S0894-7317(03)00335-3.

Gardin JM, Adams DB, Douglas PS, Feigenbaum H, Forst DH, Fraser AG, et al; American Society of Echocardiography. Recommendations for a standardized report for adult transthoracic echocardiography: a report from the American Society of Echocardiography's Nomenclature and Standards Committee and Task Force for a Standardized Echocardiography Report. J Am Soc Echocardiogr 2002; 15: 275-90. doi: 10.1067/mje.2002.121536.

Duncan AM, Francis DP, Henein MY, Gibson DG. Importance of left ventricular activation in determining myocardial performance (Tei) index: comparison with total isovolumic time. Int J Cardiol 2004; 95: 211-7. doi: 10.1016/j.ijcard.2003.07.007.

Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function - a study in normals and dilated cardiomyopathy. J Cardiol 1995; 26: 357–366.

Galderisi M, Henein MY, D’hooge J, Sicari R, Badano LP, Zamorano JL, et al; European Association of Echocardiography. Recommendations of the European Association of Echocardiography: how to use echo-Doppler in clinical trials: different modalities for different purposes. Eur J Echocardiogr 2011; 12: 339-53. doi: 10.1093/ejechocard/jer051.

Jarnert C, Melcher A, Caidahl K, Persson H, Ryden L, Eriksson MJ. Left atrial velocity vector imaging for the detection and quantification of left ventricular diastolic function in type 2 diabetes. European Journal of Heart Failure 2008; 10: 1080-7. doi: 10.1016/j.ejheart.2008.08.012.

Yip G, Wang M, Zhang Y, Fung JW, Ho PY, Sanderson JE. Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition? Heart 2002; 87: 121-5. doi: 10.1136/heart.87.2.121.

Bajraktari G, Berbatovci-Ukimeraj M, Hajdari A, Ibraimi L, Daullxhiu I, Elezi Y, et al. Predictors of increased left ventricular filling pressure in dialysis patients with preserved left ventricular ejection fraction. Croat Med J 2009; 50: 543-9. doi: 10.3325/cmj.2009.50.543.

Fang NN, Sui DX, Yu JG, Gong HP, Zhong M, Zhang Y, et al. Strain/strain rate imaging of impaired left atrial function in patients with metabolic syndrome. Hypertens Res 2015 Jul 16. doi: 10.1038/hr.2015.76.

Oktay AA, Rich JD, Shah SJ. The emerging epidemic of heart failure with preserved ejection fraction. Curr Heart Fail Rep 2013; 10: 401-10. doi: 10.1007/s11897-013-0155-7.

von Bibra H, St John Sutton M. Diastolic dysfunction in diabetes and the metabolic syndrome: promising potential for diagnosis and prognosis. Diabetologia 2010; 53: 1033-45. doi: 10.1007/s00125-010-1682-3.

Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003; 42:1149–1160. doi: 10.1016/S0735-1097(03)00994-X

Henein, M., Tossavainen, E., Söderberg, S.,

Grönlund, C., Gonzalez, M., & Lindqvist, P. Left atrial strain rate

estimates PCWP. International cardiovascular forum journal 2013; 1: 25-30.

Santos AB, Kraigher-Krainer E, Gupta DK, Claggett B, Zile MR, Pieske B, et al. Impaired left atrial function in heart failure with preserved ejection fraction. Eur J Heart Fail 2014; 16: 1096-103. doi: 10.1002/ejhf.147.

Keith A. Harveian Lecture ON THE FUNCTIONAL ANATOMY OF THE HEART. Br Med J 1918 Mar 30;1(2987):361-3.

Li JK. Comparative cardiac mechanics: Laplace's Law. J Theor Biol. 1986; 118: 339-43.

Zakeri R, Chamberlain AM, Roger VL, Redfield MM. Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study. Circulation. 2013; 128: 1085-93. doi: 10.1161/CIRCULATIONAHA.113.001475.

Bajraktari, G., Lindqvist, P., & Henein, M. Y. Left ventricular global dyssynchrony is exaggerated with age. International Cardiovascular Forum Journal. 2013; 1: 47-51.

Rossi A, Gheorghiade M, Triposkiadis F, Solomon SD, Pieske B, Butler J. Left atrium in heart failure with preserved ejection fraction: structure, function, and significance. Circ Heart Fail. 2014; 7: 1042-9. doi: 10.1161/CIRCHEARTFAILURE.114.001276.

Zamora E, Lupón J, López-Ayerbe J, Urrutia A, González B, Ferrer E, et al. Left atrium diameter: a simple echocardiographic parameter with high prognostic value in heart failure. Med Clin (Barc) 2007; 129: 441-5.

Bajraktari G, Fontanive P, Qirko S, Elezi S, Simioniuc A, Huqi A, et al. Independent and incremental value of severely enlarged left atrium in risk stratification of very elderly patients with chronic systolic heart failure. Congest Heart Fail 2012; 18: 222-8. doi: 10.1111/j.1751-7133.2011.00280.x.

Yamaguchi K, Yoshitomi H, Ito S, Ito S, Adachi T, Sato H, et al. Left atrial remodeling and recurrence of congestive heart failure in patients initially diagnosed with heart failure. Echocardiography 2014; 31: 936-40. doi: 10.1111/echo.12497.

Ceresa M, Capomolla S, Pinna GD, Febo O, Caporotondi A, Guazzotti GP, et al. Left atrial function: bridge to central and hormonal determinants of exercise capacity in patients with chronic heart failure. Monaldi Arch Chest Dis 2002; 58: 87-94.

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2. DOI: 10.17987/icfj.v2i1.4






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