Biomarkers as a guide to therapy in heart failure patients

January 28, 2009

There has been much interest in the biomarker known as N-terminal brain natriuretic peptide (BNP) as a precise guide for the diagnosis, prognosis and treatment of heart failure. Earlier studies showed that this peptide released by the heart muscle in response to stress lowers blood pressure and has diuretic properties, with levels increased in patients with heart failure. Hence the interest in this peptide as a marker for the exclusion or presence and severity of heart failure.

Now, a randomised trial reported in JAMA suggests that, while using BNP as a marker to guide therapy is not associated with any improvement in all-cause outcome over conventional symptom-guided therapy, there is indeed a benefit in hospital-free survival in heart failure patients under the age of 75.

The study (Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure [TIME-CHF]) was performed in 499 patients age 60 years or older hospitalised for heart failure within the past year and with N-terminal BNP levels at least twice the upper limit of normal. The subjects were randomised to receive treatment to reduce symptoms (symptom-guided therapy) or intensive treatment to reach a BNP level of no more than twice the upper limit of normal and reduce symptoms (BNP-guided therapy). The study population was then prospectively stratified into two age groups, under and over 75 years.

After a follow-up of 18 months, the BNP-guided strategy and symptom-guided strategies had similar outcomes with respect to all-cause hospitalisation (41% vs 40%) and survival. However, survival without hospitalisation for heart failure was significantly improved with BNP-guided therapy (72% vs. 62%). This benefit was not apparent in patients over the age of 75.

Thus, the study authors suggest that "persistence in intensifying medical therapy seems to be the key for an optimal clinical outcome in patients aged 60 to 74 years, whereas it may not be beneficial to push doses to the limits in patients aged 75 years or older".

Commenting on the study on behalf of the European Society of Cardiology, Professor Kenneth Dickstein from Stavanger University Hospital in Norway emphasises the study's difference in outcome between the under and over-75s. "The older people in this study did not do as well as the younger and did not respond as well to therapy," he says. "So we still need trials properly powered to show the effect of BNP measurement as a marker in elderly patients who more closely reflect our everyday heart failure populations today. So, while we saw a benefit of intensive therapy guided by BNP levels in younger patients in this study, we didn't see it in the over-75s, who generally had more advanced disease, co-morbidity and higher BNP levels."

The study also showed that continual monitoring of BNP levels (performed at 1, 3, 6, 12 and 18 months in the BNP group) as a guide to treatment was not associated with any improvement in outcome: "A baseline measurement of BNP may be enough to initiate effective therapy," says Professor Dickstein. "Serial measurements do not appear to have added value."

European Society of Cardiology

---

---

	Success with Heart Failure (mass mkt ed): Help and Hope for Those with Congestive Heart Failure by Marc Silver (Author) Up-to-date information on available and forthcoming medical and surgical treatments. How attitude and emotion affect heart failure-and what you can do to stay positive. Tips for adopting a heart-healthy diet and lifestyle. Ways to forge a positive working relationship with your doctor or cardiologist.
	Living Well with Heart Failure, the Misnamed, Misunderstood Condition by Edward K. Kasper (Author), Mary Knudson (Author) Heart failure—the expression alone is scary. The idea that the blood-pumping organ in our chest can struggle, stutter, or suddenly stop is deeply disconcerting. But for those who get the diagnosis, the future is not necessarily bleak. With the right treatments and a healthy lifestyle that includes exercise and good nutrition, many people with heart failure can improve their condition and live well. Heart failure expert Edward K. Kasper, M.D., teams with journalist—and survivor—Mary Knudson to give readers an honest account of this misunderstood condition. The authors explain the complex science of heart failure and look critically at the care available. Living Well with Heart Failure, the Misnamed, Misunderstood Condition will help readers understand:• The causes of the...
	Heart Failure: A Companion to Braunwald's Heart Disease: Expert Consult - Online and Print, 2e (Expert Consult Title: Online + Print) by Douglas L. Mann MD FACC (Author) Dr. Douglas L. Mann, one of the foremost experts in the field, presents the 2nd Edition of Heart Failure: A Companion to Braunwald's Heart Disease. This completely reworked edition covers the scientific and clinical guidance you need to effectively manage your patients and captures the dramatic advances made in the field over the last five years. Now in full color and with convenient online access, this edition features eleven new chapters, including advanced cardiac imaging techniques, use of biomarkers, cell-based therapies and tissue engineering, device therapies, and much more. Includes access to the complete contents online, fully searchable, enabling you to consult it rapidly from any computer with an Internet connection. Incorporates an enhanced emphasis on surgical outcomes to...
	The Cleveland Clinic Guide to Heart Failure (Cleveland Clinic Guides) by Randall Starling (Author) Expert medical advice from the #1 heart center in America for 14 years in a rowFor the 5 million people with heart failure, there’s new reason for hope: recent medical advances have revolutionized how this condition is managed.In The Cleveland Clinic Guide to Heart Failure, Dr. Randall Starling, one of the foremost authorities on heart health, provides authoritative advice to help people survive heart failure and enjoy a good quality of life. This comprehensive resource gives readers the cutting-edge medical guidance Dr. Starling offers his patients, including: Insight into what causes heart failure; The latest breakthrough studies – and what those discoveries mean for the future of this disease; Reliable guidance on diagnostic tests and treatment options; Personal...
	Management of Heart Failure by Barry Greenberg (Editor), Denise Barnard (Editor), Sanjiv Narayan (Editor), John Teerlink (Editor) This volume presents a fresh international perspective on current approaches to treating heart failure. An accessible reference for hospital-based specialists, the book provides an update on recent advances in therapeutics and pharmacology, as well as ongoing trials. Four major sections concentrate on a review of screening, assessment and diagnosis; an update on drug treatments; an update on device therapy; and a description of best practice recommendations for managing clinically challenging cases
	Oxford Textbook of Heart Failure (Oxford Textbooks in Cardiology) by Theresa A. McDonagh (Author), Roy S. Gardner (Author), Andrew L. Clark (Author), Henry Dargie (Author) Although the incidence of coronary heart disease is falling, its major complication, heart failure, is increasing in frequency. All health care practitioners will encounter patients with heart failure, presenting either acutely or in need of chronic heart failure management. However with recent advances in medical therapy, the prognosis of the condition has improved dramatically so that whereas once heart failure was a pre-terminal diagnosis, now for many it is treatable. Taking the reader from an understanding of the basic mechanisms of heart failure through to an appreciation of the complexities of heart failure management and the remarkable improvements possible with good treatment, this definitive textbook is written by internationally renowned leaders in their field and...
	Heart Failure: Pathophysiology, Molecular Biology, and Clinical Management (HEART FAILURE: PATHOPHYSIOLOGY, MOLEC BIOL & CLIN MGT) by Arnold M. Katz MD (Author), Marvin A. Konstam (Author) This Second Edition of Dr. Katz's highly acclaimed text has been thoroughly revised to incorporate the latest advances in the study and treatment of heart failure. The book explains the pathophysiology, molecular mechanisms, clinical manifestations, and therapy of heart failure in an integrated, reader-friendly manner that is accessible to both clinicians and basic scientists. More than 100 illustrations, most created for this book by the authors, complement the text. This edition has been completely reorganized. Chapters describe the hemodynamic basis for the clinical manifestations of heart failure; the neurohumoral responses in heart failure and key signaling pathways that mediate functional responses; the proliferative responses in failing hearts; the cellular and molecular...
	Heart Failure in Clinical Practice by Michael Y. Henein (Editor) Heart Failure in Clinical Practice provides a toolkit for clinicians to guide them in the diagnosis and treatment of patients with suspected heart failure. Algorithms and flow diagrams are included to give the reader an illustrated snapshot of the decisions involved in the management of these patients.
	Mechanical Circulatory Support: A Companion to Braunwald's Heart Disease: Expert Consult: Online and Print, 1e by Robert L. Kormos MD FRCS(C) FACS FAHA (Author), Leslie W. Miller MD (Author) Mechanical Circulatory Support, by Drs. Robert L. Kormos and Leslie W. Miller, provides the clinically relevant information you need to effectively use this therapy to treat and manage end-stage cardiovascular disease. In this Companion to Braunwald's Heart Disease, the world's most prominent experts in mechanical circulatory support (MCS) cover basic science, device construction, clinical applications, socioeconomic implications, future directions, and more. Stay on top of hot topics - including innovative devices like continuous flow pumps, next-generation centrifugal pumps, and total artificial hearts; MCS for pediatric and congenital heart disease; cellular, molecular, genomic, and functional changes that occur in the failing heart in response to MCS; and Interagency Registry of...
	Heart Failure Pocketcard Set by Anita D. Szady (Author), Anthony A. Bavry (Author) The Heart Failure pocketcard Set contains a collection of important information on the pathophysiology, diagnosis and management of heart failure including: * Neurohormonal mechanisms of heart failure and common causes of nonischemic cardio myopathy * Heart failure staging information including stage-specific treatment guidelines * The correct assessment and treatment of acute decompensate heart failure * A PRIDE score- and BNP level-based algorithm for the management and triage of patients with suspected acute congestive heart failure * Instructions on the initial evaluation of patients with heart failure including history and physical and laboratory data information * AHA/ACC/HRS guidelines on cardiac defibrillation and resynchronization therapy * Pharmacologic therapy...