Running head: OUTCOME RESEARCH ON CHF

Treatment of CHF based on BNP levels versus Symptoms Hannah Dowling University of South Florida

OUTCOME RESEARCH ON CHF

Treatment of CHF based on BNP levels versus Symptoms

Congestive Heart Failure (CHF), as it is commonly known, is more correctly termed left heart failure and can further be divided into systolic and diastolic failure, with systolic heart failure being seen most often. It is estimated that in American adults over age 65, up to 10% suffer from symptomatic heart failure (McCance, Huether, Brashers & Rote, 2010) and it is the most common reason for hospital admission in that age group (Pfisterer et al., 2009). Admissions to acute care facilities for heart failure can be lowered with better diagnostic tools and better management, and will lead to much lowered healthcare costs (Kinkade & Frazier, 2006).

Congestive heart failure is multifactorial in etiology: risk factors include older age, hypertension, obesity, diabetes, renal disease, ischemic or valvular heart disease, and excessive alcohol use. Diagnosis is made using echocardiography which may show a low cardiac output and cardiomegaly. Brain natriuretic peptide (BNP) is produced and subsequently released in response to volume and pressure overload of the hearts chambers. Endogenous BNP can be measured in the serum to assist clinicians in diagnosing or differentiating heart failure, in determining a patients prognosis, and monitoring treatment of HF (McCance et al., 2010). Despite advances made in the diagnosis and treatment of CHF, the 8-year survival rate hovers around 15% overall (McCance et al., 2010). BNP is secreted from the cardiac ventricles along with the biologically inactive N-Terminal proBNP (a 76 amino acid N-terminal fragment) (McCance et al, 2010). The half-life of N-TproBNP is 1 to 2 hours, whereas that of BNP is 20 minutes, which makes it a better marker for CHF when performing diagnostic blood testing. The end effect of BNP and ANP (Atrial Natriuretic Peptide) is a decrease in cardiac output and blood volume (McCance et al., 2010).

OUTCOME RESEARCH ON CHF Background & Significance

Extensive literature review was performed using patient, intervention, comparison, outcome, and time (PICOT) strategy to answer a clinical question and to explore if treatment based on BNP levels compared to CHF symptoms decreases hospitalization and improves quality of life. The review produced six appropriate studies that focused on symptomatic and BNP-based treatment of CHF. Literature supported that therapy based on N-Terminal BNP levels did improve quality of life and decreased hospitalization for those aged 60 to 75 years, but did not improve outcomes for those over age 75 years (Pfisterer et al., 2009). When patients were treated based on BNP, or received multidisciplinary care, mortality was less in the BNP-guided and clinically-guided than the usual care group after one year. After three years, mortality was reduced in participants younger than 75 years who had BNP-guided therapy, compared with those receiving clinical management or usual care (Lainchbury et al., 2010). Similarly, the BNP group in another study had lower hospitalization rates, improved clinical outcomes, and lower mortality rates. Total hospital days were also significantly lower for patients in the BNP and multidisciplinary group than for standard care (Berger et al., 2010). BNP levels have been shown to predict mortality - after controlling for age, gender, and LVEF, patients with high NT-proBNP levels had higher mortality than those with normal NT-proBNP levels (Gustafsson et al., 2005). N-TproBNP levels have been shown to independently predict risk of heart failure and cardiovascular death, based on a statistically significant increase or decrease in N-TproBNP levels from baseline (deFilippi et al., 2010). Medication therapy has shown to decrease BNP levels: one study showed that sustained reductions in BNP levels were achieved in a large cohort with administration of daily Valsartan similar results were found with an ACE inhibitor and spironolactone together (Latini et al., 2002). The literature reviewed lacked current studies on CHF treatment as it relates to patients quality of life, and the efficacy of long-term management of CHF patients by way of N-TproBNP levels. Although literature indicates BNP-level guided therapy reduces hospital admissions, further research is needed until standardized use and recommendations for N-TproBNP can be issued. However, more research is needed into what constitutes multidisciplinary care, follow-up intervals, correlation of

OUTCOME RESEARCH ON CHF symptoms and BNP levels, the cost of interventions and the impact that outpatient management using

BNP measurements and symptom-guided therapy could have financially. It is well known that CHF is an incredibly costly disease process with high mortality. If a standardized treatment/management plan is to be established for clinicians across the US, further research into the cost of the therapies discussed must be done. Further studies should be done, perhaps taking an inventory of patients symptoms leading up to and after a diagnosis of CHF, using a Likert scale to determine the perceived severity of particular symptoms such as shortness of breath, fatigue, an amount of pillows used to sleep. These symptoms can then be correlated with serial N-TproBNP levels for each patient to allow a much more accurate idea of when a patient may be in acute heart failure or heading towards a crisis. Theory The Theoretical Framework to be used for this study is Betty Neumans Health Care Systems Model, first developed in 1970. This model focuses on the response of the patient to potential or actual environmental stressors and using primary, secondary, and tertiary interventions to achieve maximum wellness for each patient (Polit & Beck, 2012). This model was chosen because it can be applied to a variety of patients with chronic and acute illnesses, in a wide variety of settings, such as our Chronic Heart Failure patients as inpatients and outpatients. The model allows that patients react to stress with resistance and defense, and use continuous feedback loops to refine the response and stabilize. Because patients are constantly interacting with the environment and have a reciprocal relationship, the goal is to gain optimal balance, through nursing interventions. Although the participants in this study have already been diagnosed with CHF, they can still benefit from many interventions. Primary interventions include education on diet, exercise, and healthy choices. Secondary interventions focus on avoiding an acute exacerbation of CHF, such as taking medications as prescribed and maintaining a low-salt diet. Tertiary interventions include management of the symptoms of CHF, checking BNP levels, and medications for CHF such as diuretics. The patient can achieve a maximal state of health by balancing their diet, medications, and exercise, and hopefully prevent more hospital admissions for acute CHF.

OUTCOME RESEARCH ON CHF Research Method Design and Sample: A longitudinal, randomized controlled trial will be performed at a single

clinical site. Participants will be randomly assigned using a computer program to one of three groups: the first group will be clinically managed based on N-TproBNP levels alone, the second group will be managed based on symptoms alone, and the third group will be managed using a combination of NTproBNP levels and symptoms. Inclusion and Exclusion criteria: Participants selected will be over the age of 18; with a diagnosis of CHF confirmed by symptoms, Chest X-ray, or a N-TproBNP level > 1000 pg/mL; and willing to participate. Those who are pregnant or who have heart failure related to pulmonary disease will not be selected. Setting: Tampa General Hospital, Inpatient Units, 12-72 hours after admission. Sample: 210 patients, 70 who will be assigned to the N-TproBNP group, 70 assigned to the symptoms alone group and 70 assigned to the combination group. Outcome: Number of hospital admissions (related to heart failure) in six months, and a reduction in N-TproBNP levels at discharge and after six months. Dependent Variable: BNP level, number of hospital admissions after 6 months. Independent Variable: Quality of life. Instruments used: The Kansas City Cardiomyopathy Questionnaire (KCCQ) will be used to quantify physical limitations, symptoms, self-efficacy, social interference and quality of life. The questionnaire is a new, self-administered, 23-item questionnaire and will be administered to participants in groups two and three. Staff will be trained on how to administer and explain the questionnaire to participants. Data collection: Data collected from participants will include demographics, clinical data (such as ejection fraction and NYHA classification). Trained laboratory personnel who collaborate with the Primary Investigator will collect an N-TproBNP level from each participant at the beginning of the study. Participants will ideally enroll in the study between the first and third days of admission to an acute care

OUTCOME RESEARCH ON CHF facility. Subsequent N-TproBNP levels will be done daily as part of the study while the participant is an inpatient, up until the day of discharge. After discharge, participants from each group will have NTproBNP levels also measured at 15 days, 30 days, then 2, 4, and 6 months. Procedure: The Research team will include the Principal Investigator, six Registered Nurses, lab personnel, and two administrative assistants. All involved staff members will be trained via the USF Human Subject Research Protection and will comply with USF and IRB policies. The Principal Investigator (PI) will complete the Mandatory Investigator Education Policy through USF, along with a current resume and Investigator Responsibility Certification Form. HIPPA guidelines will be followed at all times. Appropriate IRB approval forms will be submitted via eIRB. Once a letter of approval is received from the IRB, the study will proceed. Data analysis will be performed using an outcome analysis and a cost analysis model. An outcome analysis will help reveal whether or not the original goals were achieved. Cost analysis (Costbenefit analysis) will determine whether the benefits of the program outweigh the monetary costs. Costbenefit analysis (CBA) will use current and previous projects treating CHF patients and past financial data to determine the financial risk involved. Continuous variables will be analyzed with Pearson correlation coefficient, regression analysis, and ANOVA. Readmission and mortality events can be analyzed using the Cox proportional hazard regression. The questionnaires using Likert scales will be evaluated with a summated rating scale. Dissemination Plan

When the study is complete and a final report has been published, if our hypothesis is correct that the management of CHF using N-TproBNP levels along with symptomatology leads to less hospitalizations and decreased mortality, it will require a change in practice. Firstly, an education program that takes 30 minutes or less must be designed for clinicians which includes statistics and benefits of using BNP and symptoms for management of CHF. It must also include cost effectiveness and recommendations for frequency of screenings. A simple cheat sheet will be printed in color and laminated to give to clinicians to guide them while caring for CHF patients.

OUTCOME RESEARCH ON CHF In practice, most clinicians who care for patients with CHF do not rely on clinical guidelines, even though they are available. Current guidelines should be updated to include the most recent research on N-TproBNP levels and symptoms management. As always, barriers to change will include clinicians current beliefs and practices, a lack of time and willingness to learn new methods, and possibly cost. Education of key clinicians (such as medical directors, Nurse practitioners, and nurses) will assist in

achieving change in practice. After changes have been implemented, follow-up studies will be performed to determine whether more education is needed and whether clinicians are following recommendations.

OUTCOME RESEARCH ON CHF References

Berger, R., Moertl, D., Peter, S., Ahmadi, R., Huelsmann, M., Yamutti, S., Pacher, R. (2010). N-Terminal Pro B-Type Natriuretic Peptide Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure: A 3-Arm, Prospective, Randomized Pilot Study. Journal of the American College of Cardiology, 55, 645-653. doi: 10.1016/j.jacc.2009.08.078 deFilippi, C.R., Christenson, R.H., Gottdiener, J.S., Kop, W.J., & Seliger, S.L. (2010). Dynamic Cardiovascular Risk Assessment in Elderly People: The Role of Repeated N-Terminal Pro B-Type Natriuretic Peptide Testing. Journal of the American College of Cardiology, 55, 441-450. doi: 10.1016/j.jacc.2009.07.069
Green, C.P., Porter, C.B., Bresnahan, D.R. & Spertus, J.A. (2000). Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. Journal of the American College of Cardiology; 35(5), pp 1245-1255. doi:10.1016/S07351097(00)00531-3

Gustafsson, F., Steensgaard-Hansen, F., Badskjear, J., Poulsen, A.H., Corell, P., & Hildebrandt, R. (2005). Diagnostic and Prognostic Performance of N-Terminal ProBNP in Primary Care Patients With Suspected Heart Failure. Journal of Cardiac Failure, 11, S15-S20. Retrieved from http://www.journals.elsevierhealth.com/periodicals/yjcaf Lainchbury, J.G., Troughton, R.W., Strangman, K.M., Frampton, C.M., Pilbrow, A., Yandle, T.G., Richards, A.M. (2010). N-Terminal Pro B-Type Natriuretic Peptide-Guided Treatment for Chronic Heart Failure: Results From the BATTLESCARRED (NTproBNP Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) Trial. Journal of the American College of Cardiology, 55, 53-60. doi: 101.1016/j.jacc.2009.02.095

OUTCOME RESEARCH ON CHF

Latini, R., Masson, S., Anand, I., Judd, D., Maggioni, A.P., Chiang, Y.T., Cohn, J.N. (2002). Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure (Val-HeFT). Circulation, 106, 2454-2458. doi: 10.1161/01.CIR.0000036747.68104.AC McCance, K.L, Huether, S.E., Brashers, V.L., & Rote, N.S. (2010). Disorders of the Central and Peripheral Nervous Systems and the Neuromuscular Junction. Boss, B. Editor. Pathophysiology: The Biologic Basis for Disease in Adults and Children. (pp 609-610). Missouri: Mosby Elsevier. Pfisterer, M., Buser, P., Rickli, H., Gutmann, M., Erne, P., Rickenbacher, P., Brunner-La Rocca, H. (2009). BNP-Guided vs Symptom-Guided Heart Failure Therapy: The Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) Randomized Trial. Journal of the American Medical Association; 301(4), pp 383-392. Retrieved from http://find.galegroup.com.ezproxy.lib.usf.edu/gtx/retrieve Polit, D.F, & Beck, C.T. (2012). Nursing Research: Generating and Assessing Evidence for Nursing Practice (pp126-149). Philadelphia: Lippincott Williams & Wilkins.