Flow-mediated vasodilation predicts outcome in patients with chronic heart failure: comparison with B-type natriuretic peptide.

OBJECTIVES The aim of this study was to assess the predictive potency of impaired endothelium-dependent flow-mediated vasodilation (FMD) in patients with chronic heart failure (CHF). BACKGROUND Chronic heart failure is associated with reduced FMD; the prognostic impact of this observation is unknown. METHODS Seventy-five ambulatory CHF patients (United Network of Organ Sharing [UNOS] status 2) with a left ventricular ejection fraction (LVEF) < or =30%, despite optimized medical therapy (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, 100%; beta-blocker, 81%), were evaluated. Using high-resolution ultrasound, FMD of the brachial artery was assessed in addition to other neurohormonal, clinical, and hemodynamic variables. Age, gender, New York Heart Association (NYHA) functional class, LVEF, hemodynamic variables, B-type natriuretic peptide (BNP) levels, medical therapy, cardiovascular risk factors, and FMD were analyzed for prediction of the combined end point conversion to UNOS status 1 or death in a multivariate Cox model. RESULTS Up to three years, 21 patients (28%) converted to UNOS status 1, and 6 patients (8%) died. Univariate risk factors for the combined end point were log BNP (p = 0.0032), FMD (p = 0.0033), NYHA functional class (p = 0.0132), beta-blocker therapy (p = 0.0367), and mean blood pressure (p = 0.0406). In the multivariate analysis, only FMD (p = 0.0007), log BNP (p = 0.0032), and mean blood pressure (p = 0.0475) were independently related to the combined end point. In the Kaplan-Meier plot, significantly more patients with FMD <6.8% (median) reached the combined end point, as compared with patients with FMD >6.8% (p = 0.004). CONCLUSIONS In CHF, impaired FMD is a strong, independent predictor of conversion to UNOS status 1 or death.

[1]  Amir Lerman,et al.  Coronary Endothelial Dysfunction Is Associated With an Increased Risk of Cerebrovascular Events , 2003, Circulation.

[2]  M. Komajda,et al.  Risk stratification in chronic heart failure. , 1998, European heart journal.

[3]  C. Jones,et al.  Endothelial control of arterial distensibility is impaired in chronic heart failure. , 1995, Circulation.

[4]  Massimo Chiariello,et al.  Endothelial Dysfunction and Cardiovascular Risk Prediction in Peripheral Arterial Disease: Additive Value of Flow-Mediated Dilation to Ankle-Brachial Pressure Index , 2003, Circulation.

[5]  Kamyar Kalantar-Zadeh,et al.  Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. , 2004, Journal of the American College of Cardiology.

[6]  S. Anker,et al.  Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure , 2000 .

[7]  S. Higano,et al.  Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. , 2000, Circulation.

[8]  G. Schuler,et al.  Improvement of peripheral endothelial dysfunction by acute vitamin C application: different effects in patients with coronary artery disease, ischemic, and dilated cardiomyopathy. , 2003, American heart journal.

[9]  B-type natriuretic peptide and peak exercise oxygen consumption provide independent information for risk stratification in patients with stable congestive heart failure. , 2004, Journal of the American College of Cardiology.

[10]  S. Katz Mechanisms and implications of endothelial dysfunction in congestive heart failure. , 1997, Current opinion in cardiology.

[11]  K. Swedberg,et al.  Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. , 1990, Circulation.

[12]  M. Kinoshita,et al.  Plasma oxidized low-density lipoprotein as a prognostic predictor in patients with chronic congestive heart failure. , 2002, Journal of the American College of Cardiology.

[13]  R. Zelis,et al.  Effects of NO synthase inhibition on the muscular blood flow response to treadmill exercise in rats. , 1994, Journal of applied physiology.

[14]  M. Watkins,et al.  Risk Stratification for Postoperative Cardiovascular Events via Noninvasive Assessment of Endothelial Function: A Prospective Study , 2002, Circulation.

[15]  William D. Dupont,et al.  PS power and sample size program available for free on the internet , 1997 .

[16]  H. Drexler,et al.  Endothelial dysfunction in human disease. , 1999, Journal of molecular and cellular cardiology.

[17]  R. Berger,et al.  B-Type Natriuretic Peptide Predicts Sudden Death in Patients With Chronic Heart Failure , 2002, Circulation.

[18]  Michael T. Watkins,et al.  Predictive value of noninvasivelydetermined endothelial dysfunction for long-term cardiovascular events inpatients with peripheral vascular disease , 2003 .

[19]  R. Berger,et al.  Effects of Endothelin A Receptor Blockade on Endothelial Function in Patients With Chronic Heart Failure , 2001, Circulation.

[20]  W. Laskey,et al.  Arterial wave reflection in heart failure. , 1987, Circulation.

[21]  E. Benjamin,et al.  Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. , 2002, Journal of the American College of Cardiology.

[22]  D. Mancini,et al.  Mortality remains high for outpatient transplant candidates with prolonged (>6 months) waiting list time. , 1999, Journal of the American College of Cardiology.

[23]  P. Poole‐Wilson,et al.  Exercise limitation in chronic heart failure: central role of the periphery. , 1996, Journal of the American College of Cardiology.

[24]  J. Schroeder,et al.  Analysis of deaths in patients awaiting heart transplantation: impact on patient selection criteria. , 1996, Heart.

[25]  D. Fukai,et al.  Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. , 1997, Circulation.

[26]  E. Oechslin,et al.  Endothelial control of vascular tone in chronic heart failure. , 1998, Journal of Cardiovascular Pharmacology.

[27]  Arturo Pujia,et al.  Prognostic significance of endothelial dysfunction in hypertensive patients. , 2001 .

[28]  G. Maurer,et al.  Value of cardiopulmonary exercise testing and big endothelin plasma levels to predict short-term prognosis of patients with chronic heart failure. , 1998, Journal of the American College of Cardiology.

[29]  D. Renlund,et al.  New UNOS rules: historical background and implications for transplantation management. United Network for Organ Sharing. , 1999, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[30]  T. Marwick,et al.  Vascular dysfunction and heart failure: epiphenomenon or etiologic agent? , 2002, American heart journal.

[31]  A M Zeiher,et al.  Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. , 2000, Circulation.

[32]  C. Stefanadis,et al.  Endothelial function and proinflammatory cytokines in patients with ischemic heart disease and dilated cardiomyopathy. , 2004, International journal of cardiology.

[33]  A. Ignaszewski,et al.  The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. , 2003, Journal of the American College of Cardiology.

[34]  M. Komajda,et al.  Combination of B-type natriuretic peptide and peak oxygen consumption improves risk stratification in outpatients with chronic heart failure. , 2003, American heart journal.