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Running head: CONGESTIVE HEART FAILURE Treatment Guidelines for Congestive Heart Failure Kelly Strine and Jenifer Smith State University of New York Institute of Technology 1 CONGESTIVE HEART FAILURE 2 Treatment Guidelines for Congestive Heart Failure Heart failure is a complex disease process that often involves several body systems and requires a multidisciplinary approach to care that involves the patient, caregiver, and healthcare professionals. According Yancy et al. (2013), heart failure is often a result of poorly managed or uncontrolled cardiac diseases such as hypertension, atrial fibrillation, coronary artery disease, myocardial infarction, diabetes mellitus, and obesity. Heart failure is the most common Medicare diagnosis with more money spent on the diagnosis and treatment than any other diagnosis. Heart failure affects approximately five million.. Heart failure is the main diagnosis of 12 to 15 million office visits and 80% of hospitalized patients greater than 65 years. The number of deaths from heart failure has increased despite advances in treatment. In addition to mortality, poorly managed heart failure can lead to a significant long-term disability from complications such as myocardial infarction, cerebral vascular attacks, and end-stage renal disease (Yancy, 2013). The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) has developed guidelines for the detection, management, and treatment of congestive heart failure based on data from clinical trials. Management of heart failure includes: correcting the underlying cause for failure, improving cardiac muscle, reducing the workload of the heart, controlling arrhythmias, reducing physical and emotional stress, and limiting excessive salt and water (Cerlo, 2001). According to McMurray (2010), the goal of heart failure management is to decrease symptoms, reduce hospitalizations and prevent premature death. Treatment of underlying structural heart disease and the management of comorbidities such as diabetes mellitus, hypertension, and hyperlipidemia is essential to prevent the progression of heart failure. The disease management of heart failure includes both pharmacological and nonpharmacological guidelines and requires a collaborate effort among health care professionals. CONGESTIVE HEART FAILURE 3 The treatment of heart failure may be optimized by closely examining the results of clinical trials and using evidence-based guidelines. The purpose of this article is to describe the results of a literature review of disease management strategies for heart failure. An electronic search was conducted in February 2014 using the New England Journal of Medicine, the Agency for Healthcare Research and Quality’s National Guideline Clearing House, and ProQuest. The search headings included: congestive heart failure, heart failure, systolic heart failure, diastolic heart failure, disease management of heart failure, evidence-based guidelines for treatment of heart failure, epidemiology, diuretics, and nitrates. A total of 22 articles were reviewed for relevance to the disease management of heart failure. Pharmacological Treatment Guidelines Angiotensin Converting Enzyme Inhibitors Angiotensin-converting enzyme inhibitors (ACE) are the first-line pharmacological treatment for patients with systolic heart failure and should be started upon diagnosis and continued indefinitely unless contraindicated by renal function, angioedema, or hyperkalemia (Yancy et al., 2013) . Two large clinical trials showed that patients with NYHA class II, III, and IV heart failure treated with enalapril compared to placebo in addition to diuretics had reduced hospitalization and decreased mortality rates (Fu et al., 2012); (Mujib et al., 2013); (Yancy et al., 2013). In placebo-controlled trials, enalapril therapy reduced the risk of developing symptomatic heart failure among NYHA class I patients with left ventricular systolic function. Treatment with ACE inhibitors is recommended to all patients with left ventricular systolic dysfunction regardless of NYHA classification (McMurray, 2010). Renal function and electrolytes should be monitored with each dose adjustment (National Collaborating Centre for Acute and Chronic Conditions, 2010). CONGESTIVE HEART FAILURE 4 Beta-blockers Along with ACE inhibitors beta-blockers are first-line therapy in patients with systolic heart failure regardless of the cause of the condition. Beta-blockers improve systolic dysfunction, increases the EF 5-10%, and reduces symptoms (Yancy et al., 2013). In three placebo-controlled trials, beta-blocker therapy with bisoprolol, carvedilol, or metoprolol succinate reduced the rate of hospitalization and reduced mortality by 34% when used with ACE inhibitors, diuretics, and digoxin among patients with NYHA class II, III, or IV. The CHARM-Preserved study compared candesartan with placebo in NYHA class II, III, or IV and an EF greater than 40% had improved outcomes and decreased mortality with candesartan. Another study, involving patients with previous myocardial infarction and diastolic heart failure showed that treatment with propranolol reduced mortality (Aurigemma et al, 2004). El-Refai et al. (2013) found in their retrospective cohort study that beta-blockers were cardio-protective and decreased all-cause rehospitalization in heart failure patients with preserved ejection fraction. In addition, beta-blockers are an important aspect of rate control of tachycardia and atrial fibrillation. Tachycardia increases oxygen demand and decreases coronary perfusion, which may lead to ischemia without obstructive coronary artery disease. (Aurigemma et al, 2004). Diuretics The use of diuretics provides rapid relief of fluid retention and dyspnea and is the primary treatment of patients with heart failure (Felker et al., 2011). The requirements of diuretics increase and decrease based on the patient’s condition (McMurray, 2010). When diuresis is inadequate the following therapy can be considered: increasing the dose of loop diuretic, addition of a second diuretic, or a continuous infusion of loop diuretic (Hunt et al, 2005). In a prospective, double-blind randomized study among patients receiving intravenous loop diuretics, there was no CONGESTIVE HEART FAILURE 5 significant differences in symptoms when diuretic therapy was administered by bolus or continuous infusion. (Felker et al., 2011). In the same study, there was also found to be no significant difference between the low dose strategy and the high dose strategy in the efficacy or safety end points. Patients with high doses were found to have quicker resolution of their dyspnea with high dose treatments. Angiotensin Receptor Blockers The efficacy of Angiotensin-Receptor Blockers (ARBs) is similar to ACE inhibitor in a large trial in which candesartan was used (Patel et al., 2012). ARBs are more expensive than ACE inhibitors and are recommended as an acceptable alternative to patients that develop a cough with ACE inhibitor therapy. ARBs is also recommended in conjunction with ACE inhibitors and beta-blockers in patients who have persistent symptoms in NYHA class II, III, or IV. In two placebo-controlled randomized trials, the addition of an ARB reduced hospitalization for heart failure by 17% for valsartan (Patel et al., 2012); (Mujib et al., 2013) . Candesartan reduced the risk of cardiovascular mortality by 16% (Patel et al, 2012). Aldosterone Receptor Antagonists According to large, placebo-controlled randomized trials the addition of spironolactone in addition to diuretic, digoxin, and ACE inhibitors reduced hospitalizations and had a 30% reduction in mortality in NYHA class III and IV (McMurray, 2010). The addition of aldosterone antagonists should be considered in class III and IV patients who remain symptomatic despite being treated with an ACE or ARB, diuretics, and a beta-blocker. Patients should be either on an aldosterone antagonists or an ARB but not both at the same time due to the risk of hyperkalemia and renal dysfunction. An aldosterone antagonist may be added to an ACE inhibitor (McMurray, 2010). CONGESTIVE HEART FAILURE 6 Hydralazine and Isosorbide Dinitrate The Vasodilator Heart Failure Trial (V-HeFT I) demonstrated increased efficacy of combining nitric oxide isosorbide dinitrate with hydralazine in patients with mild-to-severe heart failure (McMurray, 2010). A retrospective subgroup analysis from two clinical trials of hydralazine and isosorbide dinitrate suggested that black patients did not respond as well to ACE inhibitors (McMurray, 2010). Studies show that African-American individuals have a less active reninangiotensin system and a lower bioavailability of nitric oxide than Caucasians. The AfricanAmerican Heart Failure Trial (A-HeFT) conducted a randomized, placebo-controlled, doubleblind trial with patients from 161 centers in the United States. A total of 1050 black patients with NYHA class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo, in addition to standard treatment for heart failure. The study terminated early due to increased mortality of the placebo group. The results of the study concluded that the addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard heart failure therapy is more effective in black patients (Taylor et al., 2004). Digoxin Digoxin has shown improvement in patient’s symptoms and exercise tolerance in patients with mild-to-moderate heart failure regardless of underlying rhythm or concomitant therapy. Digoxin has been shown in 2 separate studies to reduce 30 day all cause readmission when use in systolic heart failure (Ahmed, Bourge, Fonarow, Patel, Morgan, & Fleg, 2014; Bart, Goldsmith, Lee, Givertz, O'Connor, & Bull, 2012). Digoxin is considered an adjunct to therapy in patients with persistent symptoms despite other medical management. CONGESTIVE HEART FAILURE 7 Inotropic Support Intravenous nitroglycerin relieves dyspnea in decompensated heart failure especially when ischemia is involved. Patients with reduced systolic function may have improved quality of life with inotropic therapy but should only be used for short-term management (Goodlin, 2009). Intravenous inotropics are indicated when there is evidence of hypoperfusion and obvious elevated cardiac filling pressures to maintain systemic perfusion and preserve organ function until a more definitive therapy is found (Hunt et al, 2005). Warfarin and Aspirin A double-blind, multi-center trial at 168 centers in 11 countries sponsored by the National Institute of Health compared warfarin with aspirin therapy in patients with systolic heart failure in sinus rhythm. The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) study showed no significant differences between the two medications. The reduced risk of ischemic stroke with warfarin was outweighed by an increased risk of significant hemorrhage. The results of the study indicate the choice between warfarin and aspirin should be individualized with benefit outweighing the risk (Homma et al., 2012). Non-pharmacological Treatment Guidelines Pharmacological treatment has a significant role in the treatment of heart failure, but it should be used in conjunction with non-pharmacological lifestyle management such as: dietary therapy, physical activity, smoking cessation, and moderation in alcohol consumption. Smoking Cessation Tobacco use is strongly associated with the development of heart failure. Clinicians should strongly advise their patients not smoke and provide smoking cessation counseling and interventions (Yancy et al., 2013). In a retrospective study of the Survival and Ventricular CONGESTIVE HEART FAILURE 8 Enlargment (SAVE) randomized control study, it was found that those who had a myocardial infaction complicated by left ventricular dysfunction had a nearly 40% lower hazard of all-cause mortality and a 30% lower chance of death or recurrent MI or heart failure hospitalization compared to persistent smokers (Shah et al., 2010). Dietary Restriction A combination of healthy dietary patterns with reduced sodium intake and reduced body fat reduces an individual’s risk of developing hypertension, cardiovascular disease and diabetes. A diet high in sodium is strongly correlated with the development of hypertension and the progression of heart failure. Sodium intake initiates an auto-regulatory sequence that increases intravascular fluid volume affecting cardiac output, peripheral resistance, and elevating blood pressure (Sacks & Campos, 2010). Restricting sodium and fluid intake improves fatigue and edema and may reduce the need for diuretics. Obesity contributes to the pathogenesis of hypertension and The American Heart Association (AHA) guidelines have a target BMI of less than 25 to reduce the risk of heart disease. However, heart failure patients that have a BMI between 30-35 kg/m2 have reduced hospitalizations and mortality rates (Yancy, 2013). The AHA recommend a diet similar to the Dietary Approaches to Stop Hypertension (DASH) or 1.5 gm of sodium, limiting alcohol beverages to two daily for men and one for women, and a Mediterranean-style diet (Sacks et al, 2010). Patients should be given written instructions on how to adopt healthy diet such as the DASH diet, or a Mediterranean-style diet. Strict fluid restrictions does not appear to benefit patients unless they are diuretic resistant or have hyponatremia. Fluid restrictions of two liters a day is adequate for hospitalized patients. Fluid restrictions along with sodium restrictions enhances volume management and may CONGESTIVE HEART FAILURE 9 reduce the dose of diuretic needed. Patients in hot climates with low-humidity are at high risk of heat stroke if on fluid restrictions (Yancy et al., 2013). Physical Activity Controlled clinical trials show that supervised exercise training programs lessen symptoms, increases exercise tolerance, improves the quality of life, and reduces hospitalizations and mortality. In these studies, physical conditioning is achieved through formal exercise training programs which require patients to gradually increase their activity. The goal is to achieve a workloads of 40% - 70% of maximal effort for 20 to 45 minutes three to five times a week for eight to 12 weeks (Hunt et al, 2005). The ACC/AHA guidelines recommend exercise training for all stable outpatients with chronic heart failure who are able to participate. Exercise programs are intended to be individualized based on disease progression, medical management, and hemodynamic monitoring. The safety of an exercise program is monitored by heart rate, electrocardiogram, blood pressure, and patient’s rate of perceived exertion (Certo, 2001). Internal Cardiac Defibrillator According the Framingham studies 60% of the deaths that occur among patients with mild systolic heart failure are related to a ventricular arrhythmia. An implantable cardioverterdefibrillator (ICD) reduces the risk of death with no adverse effects on the quality of life. An ICD is indicated for secondary prevention in any patient that survives an unprovoked episode of ventricular fibrillation or sustained ventricular tachycardia. The Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) showed a relative 3% decrease in mortality in patients after myocardial infarction and EF less than or equal to 30% receiving a ICD implant, in addition to the standard of the care (Yancy, 2013). ICD implantation is indicated for primary prevention in NYHA class II or III who have an ejection fraction of 35% or less despite optimal CONGESTIVE HEART FAILURE 10 medical management. ICD devices should be reserved for patients that and are expected to live for at least one year and have a reasonable quality of life (McMurray, 2010). Cardiac Resynchronization Therapy Cardiac resynchronization therapy (CRT) reduces the morbidity and mortality in patients with chronic systolic heart failure and a wide QRS complex (Ruschitzka et al., 2013). CRT with atrial-synchronized biventricular pacing immediately improves stroke volume and reduces mitral regurgitation improving cardiac output. CRT is recommended for NYHA class III or IV with an ejection fraction of 35% or less, sinus rhythm, and a QRS of 120 milliseconds or more. Patients with NYHA class I or II with ejection fraction of 30% or less, a wide QRS interval greater than 130 milliseconds benefit from CRT, in addition to implantable cardioverter defibrillator. Biventricular Pacing The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) conducted a multicenter, randomized double-blinded trial involving 691 patients with indication for ventricular pacing for atrioventricular block, EF less than or equal to 50%, and mild-to-moderate heart failure. The results of the BLOCK HF trial reveal that biventricular pacing is superior to conventional right ventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction with NYHA class I, II, or III heart failure (Curtis, Worley, Adamson, Chung, Niazi, Sherfesee, Shinn, & Sutton, 2013). Rhythm Control versus Rate Control Atrial fibrillation with excessive ventricular rate results in the loss of atrial contraction and irregular filling times. Atrial fibrillation with rapid ventricular rate negatively impacts patients with heart failure and increases the risk of mortality. A multicenter, randomized trial compared the benefits of restoring sinus rhythm to rate control of atrial fibrillation in patients with heart CONGESTIVE HEART FAILURE 11 failure. A total of 1376 patients enrolled and progress followed for 37 months. The results denote that rhythm control did not reduce morbidity compared to the rate-control strategy. Medical management of patients with heart failure and atrial fibrillation should include ratecontrol. Patients with heart failure are at increased risk for adverse events from antiarrhythmic drugs and need to be examined frequently for side effects (Roy et al, 2008). Coronary-Artery Bypass Surgery According to the Surgical Treatment for Ischemic Heart Failure (STICH) trial, coronaryartery bypass grafting (CABG) is the treatment of choice for patients with heart failure and coronary artery disease. The STICH trial was a randomized multi-center, non-blinded study conducted between 2002 and 2007 at 127 clinical sites in 26 countries. Eligible patients had coronary artery disease and an EF of 35% or less. The trial compared medical therapy alone with medical therapy in addition to CABG. The mortality rate from cardiovascular causes was lower among the group assigned to CABG compared to those assigned to receive medical therapy alone (Velezquez et al, 2011). Ventricular Assist Ventricular assist devices (VAD) have evolved over the past 50 years and are still an acceptable solution for patients with advanced heart failure refractory to medical management. VAD may be used short-term for the management of acute decompensated unstable heart failure that has not responded to inotropic medications. VAD provide an opportunity to discuss further disease management such as cardiac surgery, permanent VAD, or palliative care. VAD are most commonly used as a bridge to cardiac transplant. VAD devices are also used in patients that do not meet transplantation requirements. CONGESTIVE HEART FAILURE 12 Ultrafiltation Ultrafiltration can be used as an alternative strategy to diuretic therapy is patients with acute decompensated heart failure and impaired renal function. Venous ultrafiltration is an alternative method that has advantages over diuretic therapy because the rate and volume of fluid removed can be controlled. A randomized trial of hospitalized patients with acute decompensated heart failure, worsening renal function, and persistent congestion compared ultrafiltration with a tiered pharmacological-therapy algorithm. The Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) randomly assigned patients to ultrafiltration (94 patients) with pharmacologic therapy (94 patients). The study determined that the patients in the ultrafiltration group had a higher rate of adverse events and the pharmacologic-therapy algorithm had a similar amount of fluid loss with preserved renal function after 96 hours (Bart et al., 2012). Heart Transplant Heart transplantation is a last resort for patients that have exhausted medical management. Cardiac transplant is the gold standard for refractory end-stage heart failure. Consider referral to a specialist for evaluation of cardiac transplant for patients with severe, refractory symptoms or cardiogenic shock. Advances in immunosuppressant therapy increased the five year survival rate to 71.7%. (Yancy et al., 2013). Pediatric Heart Failure Heart failure is considerably different in the pediatric population. The main causes of cardiac failure in children are congenital cardiac malformations and complex congenital heart (Hsu & Pearson, 2009). Cardiomyopathies are the most common cause of heart failure in children with structurally normal hearts (Hsu & Pearson, 2009). Congenital heart disease caused by structural malformations are more common with adult heart failure and include issues with CONGESTIVE HEART FAILURE 13 volume overload, pressure overload, or a combination of both when complex malformations are involved (Hsu & Pearson, 2009) . Non-structural causes such as primary cardiomyopathy are loss common than structural disease but is places the child at greater risk of heart failure (Hsu & Pearson, 2009). When classifying heart failure, the NYHA Heart Failure Classification is no longer applicable in the pediatric populations. The Ross Heart Failure Classification was developed to assess infants with heart failure (Hsu & Pearson, 2009). Scores for the Ross Classification are based on feeding difficulties, growth and development, and exercise intolerance (Hsu & Pearson, 2009). For children and adolescents, the New York University Pediatric Heart Failure Index was developed (Hsu & Pearson, 2009). These scores were weighted on physiological indicators and medical therapy (Hsu & Pearson, 2009). The symptoms of heart failure in the pediatric populations include growth failure, respiratory distress, and exercise intolerance. When treating heart failure in children, the underlying cause and the child’s age are what determine treatment. As with adult patients treatment goals include correction of the underlying problem, minimize morbidity and mortality, and improving functional status and quality of life (Hsu & Pearson, 2009). Due to the limited amount of research that has been established in the way of pediatric heart failure due to the protected population, the single practice guideline that is available, which was established by the International Society for Heart and Lung Transplantation, does not have any level A evidence and only 7 level B studies (Hsu & Pearson, 2009) . Most of the guidelines are based upon expert opinion. Treating the underlying cause of the heart failure when structure defects are presents seem to be the consensus of the expert opinion. When treatment must be medically managed or co-managed, it is recommended based on expert opinion that diuretics, digitalis, and ACE inhibitors are used and beta-blockers are CONGESTIVE HEART FAILURE 14 avoided (Hsu & Pearson, 2009). With volume overloaded heart failure, furosemide is the drug of choice in the pediatric population (Hsu & Pearson, 2009). Thiazide diuretics have not been tested as monotherapy in the pediatric population (Hsu & Pearson, 2009). Due to the low rate of sudden death in children awaiting heart transplantation, implantable cardiac defibrillator with left ventricular dysfunction is not indicated (Hsu & Pearson, 2009). There is little evidence or long term trials with biventricular pacing in children with heart failure although some evidence shows biventricular pacing improves functional status (Hsu & Pearson, 2009) . Ventricular Assist Devices (VAD) has shown as a successful bridge in up to 80% of children awaiting transplantation (Hsu & Pearson, 2009). Heart transplantation remains the gold standard of treatment for end-stage heart failure in children (Hsu & Pearson, 2009). Nutritional support may be just as important in pediatric heart failure patients. Sodium restrictions are not recommended in infants and young children as sodium in often not in surplus in formulas and sodium is needed as an important growth factor (Hsu & Pearson, 2009). Children can also benefit from regular physical activity, just as adults with heart failure who undergo exercise training (Hsu & Pearson, 2009). Heart failure is a complex disease that involves multisystem modalities. It is not only important for management to occur by the cardiology through thorough medication management, but a multidisciplinary approach is necessary. The American Heart Association along with the American College of Cardiologist has established guidelines for the management of heart failure including pharmacologic as well as non-pharmacologic means. While prevention of heart failure is the best way to manage heart failure, early detection of heart disease can help prevent worsening of the disease process and further management of heart failure. CONGESTIVE HEART FAILURE 15 References Ahmed, A., Bourge, R. C., Fonarow, G. C., Patel, K., Morgan, C. J., Fleg, J. L., … Allman, R. M. (2014). Digoxin use and lower 30-day all-cause readmission for Medicare beneficiaries hospitalized for heart failure. The American Journal of Medicine, 127(1), 61-70. Aurigemma, G. P., & Gaasch, W. H. (2004). Diastolic heart failure. The New England Journal of Medicine, 351(11), 1097-1105. Bart, B. A., Goldsmith, S. R., Lee, K. L., Givertz, M. M., O'Connor, C. M., Bull, D. A.,… Bourge, R. C., Fleg, J. L., Fonarow, G. C., Cleland, J., McMurray, J. V., VanVelduisen, D. J.,… Ahmed, A. (2013). Digoxin reduces 30-day all-cause hospital admission in older patients with chronic systolic heart failure. The American Journal of Medicine, 126(8), 701-708. Braunwalk, E. (2012). Ultrafiltration in decompensated heart failure with cardiorenal syndrome. The New England Journal of Medicine, 367(24), 2296-2304. doi:10.1056/ Cardiology, 34(5), 386-395. doi: 10.1016/j.jacc.2009.02.078. Cardiopulmonary Physical Therapy Journal, 12(2), 39-45. Certo, C. (2001, June). Guidelines for exercise prescription in congestive heart failure. Chaudhry, S. I., Mattera, J. A., Spertus, J. A., Herrin, J., Lin, A., Phillips, C. O.,… Krumholz, H. M. (2010). Telemonitoring in patients with heart failure. The New England Journal of Medicine, 363(24), 2301-2309. doi:10.1056/NEJMoa1010029. Curtis, A. B., Worley, S. J., Adamson, P. B., Chung, E. S., Niazi, I., Sherfesee, L.,… Suttong, M. (2013). Biventricular pacing for atrioventricular block and systolic dysfunction. The New England Journal of Medicine, 368(17), 1585-1593. doi:10.1056/NEJMoa1210356. decompensated heart failure: HFSA 2010 comprehensive heart failure practice guideline. CONGESTIVE HEART FAILURE 16 El-Refai, M., Peterson, E. L., Wells, K., Swadia, T., Sabbah, H. N., Spertus, J. A.,… Lanfear, D. E. (2013). Comparison of beta-blocker effectiveness in heart failure patients with preserved ejection fraction versus those with reduced ejection fraction. Journal of Cardiac Failure, 19(2), 73-79. doi:10.1016/j.cardfail.2012.11.011 Felker, G. M., Lee, K. L., Bull, D. A., Redfield, D. A., Stevenson, L. W., Goldsmith, S. R., … O'Connor, C. M. (2011). Diuretic strategies in patients with acute decompensated heart failure. The New England Journal of Medicine, 364(9), 797-805. Fu, M., Zhou, J., Sun, A., Zhang, S., Zhang, C., Yunzeng, A.,… Ge, J. (2012). Efficacy of ACE inhibitors in chronic heart failure with preserved ejection fraction-A meta analysis of 7 prospective clinical studies. International Journal of Cardiology, 155, 33-38. doi:10.1016/j.ijcard.2011.01.081 Galin, I., & Baran, D.A. (2003, September). Congestive heart failure: Guidelines for the primary care physician. The Mount Sinai Journal of Medicine, 70(4), 251-264. Gjesdal, K., Feyzi, J., & Olsson, S. B. (2008). Digatalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data. Heart, 94, 191-196. Goodlin, S.J. (2009). Palliative care in congestive heart failure. Journal of American College of Homma, S., Thompson, J. L., Pullicino, P. M., Freudenberger, R. S., Teerlink, J. R., Ammon, S. E., …Buchsbaum, R. (2012). Warfarin and aspirin in patients with heart failure and sinus rhythm. The New England Journal of Medicine, 366(20), 1859-1869. Hsu, D. T., & Pearson, G. D. (2009). Heart failure in children part 1: History, etiology, and pathophysiology. Circulation, 2, 63-70. doi:10.1161/CIRCHEARTFAILURE.108.820217 CONGESTIVE HEART FAILURE 17 Hsu, D. T., & Pearson, G. D. (2009). Heart failure in children part 2: Diagnosis, treatment, and furture directions. Circulation, 2, 490-498. doi:10.1161/CIRCHEARTFAILURE.109.856229 Lindenfield, J., Albert, N.M., Boehmer, J.P., Collins, S.P., Ezekowitz, J.A., Givertz, M.M., … McMurray, J. V. (2010). Systolic heart failure. The New England Journal of Medicine, 362(3), 228-238. Mujib, M., Patel, K., Fonarow, G. C., Kitzman, D. W., Zhang, Y., Aban, I. B.,….Ahmed, A. (2013). Angiotensin-converting enzyme inhibitors and outcomes in heart failure and preserved ejection fraction. The American Journal of Medicine, 126(5), 401-410. doi:10.1016/j.amjmed.2013.01.004 NEJMoa1210357. New England Journal of Medicine, 364(17), 1607-161. doi:10.1056/NEJMoa1100356. Patel, K., Fonarow, G. C., Kitzman, D. W., Aban, I. B., Love, T. W., Allman, R. M., … Ahmed, A. (2012). Angiotensin receptor blockers and outcomes in real-world older patients with heart failure and preserved ejection fraction: A propensity-matched inception cohort clinical effectiveness study. European Journal of Heart Failure, 14, 1179-1188. doi:10.1093/eurjhg/hfs101 Ruschitzka, F., Abraham, W. T., Singh, J. P., Bax, J. J., Borer, J. S., Brugada, J.,… Holzmeister, J. (2013). Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. The New England Journal of Medicine, 369(15), 1395-1405. Shah, A. M., Pfeffer, M. A., Hartley, L. H., Moye, L. A., Gersh, B. J., Rutherford, J. D.,...Solomon, S. D. (2010). Risk of all-cause mortality, recurrent myocardial infaction and heart failure hospitalization associated with smoking status following myocardial CONGESTIVE HEART FAILURE 18 infaction with left ventricular dysfunction. The American Journal of Cardiology, 106(7), 911-916. doi: http://dx.doi.org/10.1016/j.amjcard.2010.05.021 Taylor, A. L., Ziesche, S., Yancy, C., Carson, P., D'Agostino, R., Ferdinand, & Kohn, J. N. (2004). Combination of isosorbide dinitrate and hyrdalazine in blacks with heart failure. The New England Journal of Medicine, 351(20), 2049-2057. Velazquez, E.J., Lee, K.L., Deja, M.A., Jain, A., Sopka, G., Marchenko, A., …Ali, I.S., (2011, April). Coronary-artery bypass surgery in patients with left ventricular dysfunction. The Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., …Wilkoff, B. L. (2013). 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation, 128, e240-e327. doi:10.1161/CIR.0b013e31829e8776 CONGESTIVE HEART FAILURE 19 Appendix A Author Intervention Method Sample Main Findings Ahmed, A., Balanced 9649 medical In Medicare Bourge, R. C., Matched Cohort records of 8555 beneficiaries Fonarow, G. C., Study unique fee-for- with systolic Patel, K., service Medicare heart failure, a Morgan, C. J., beneficiaries discharge Fleg, J. L., … discharged with a prescription of Allman, R. M. primary digoxin was (2014). discharge associated with diagnosis of lower 30-day all- heart failure from cause hospital 106 Alabama readmission, hospitals which was between 1998 maintained at 12 and 2001 months, and was not at the expense of higher mortality. Aurigemma, G. Initial Randomized, The sample size Over a median P., & Gaasch, W. management of controlled trials included 3023 follow up period H. (2004). acute heart involving patients with of 36 months, failure includes patients with New York Heart patients that CONGESTIVE HEART FAILURE 20 reducing diastolic Association received the pulmonary and dysfunction functional class candesartan had venous II-IV heart significantly congestion with failure and LVEF fewer diuretics, greater than 40% supplemental were randomly oxygen, assigned to morphine, and receive nitroglycerin. candesartan Long term (n=1514, target management does 32 mg includes rate daily) or placebo control with beta- (n=1509). blockers or rate lowering calcium-channel blockers for tachycardia and atrial fibrillation to reduce myocardial oxygen demand. Revascularization hospitalizations. CONGESTIVE HEART FAILURE if myocardial ischemia is contributing to diastolic dysfunction. Control hypertension by utilizing the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Medications to improve heart failure such as ACE inhibitors, angiotensinreceptor blockers (ARB), or 21 CONGESTIVE HEART FAILURE 22 Spironolactone. The CHARM study specifically studied the use of candesartan as the ARB of choice for the treatment of heart failure. Bart, B. A., Goldsmith, S. R., Lee, K. L., Givertz, M. M., O'Connor, C. M., Bull, D. A.,… Braunwalk, E. (2012). This study discusses using ultrafiltration as an alternative strategy to diuretics for patients with decompensated heart failure in patients with cardio renal syndrome. The study is referred to as the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) and was funded by NHLBI. Ultrafiltration A randomized A total of 188 The patients in trial was used for patients with the ultrafiltration this study, acute group had a patients were decompensated higher rate of assigned heart failure and adverse events. ultrafiltration or worsening renal The patients diuretic therapy. function were receiving involved in this diuretics. The study. The study was patients were aborted in followed for 60 February 2012 days. Patients due to excess was performed at were enrolled adverse events a fluid removal between June 22, with CONGESTIVE HEART FAILURE 23 rate of 200 ml per 2008 and January ultrafiltration. hour. 27, 2012 in the Major adverse United States and events such as: Canada. worsening kidney function, bleeding, and intravenous catheter-related conditions. The 60 day mortality rate of the ultrafiltration group was 17% compared to 13% in the pharmacologic group. Bourge, R. C., Patients were Double-blind, 6800 ambulatory Digoxin reduces Fleg, J. L., randomly placebo- patients with 30-day all-cause Fonarow, G. C., assisgned to controlled chronic heart hospital Cleland, J., Digoxin or randomized failure (ejection admission in McMurray, J. V., Placebo group. clinical trial of fraction ≤45%) ambulatory older VanVelduisen, digoxin in patients with CONGESTIVE HEART FAILURE 24 D. J.,… Ahmed, patients with chronic systolic A. (2013) chronic heart heart failure. failure and reduced ejection fraction. Certo, C. (2001, June) Chaudhry, S. I., Patients received The study design The study Telemonitoring Mattera, J. A., educational was a included 1653 did not improve Spertus, J. A., materials multicenter, patients who had the outcomes for Herrin, J., Lin, developed by the randomized, recently been patients recently A., Phillips, C. Heart Failure controlled trial. hospitalized for hospitalized for O.,… Krumholz, Society of heart failure to heart failure. H. M. (2010). America. Patients undergo either Readmission for were provided telemonitoring any reason with a scale to (n=826) or usual occurred in perform weights care (n=827). 49.3% of patients if needed. The median age in the Patients were of the patients telemonitoring provided with was 61 years; group and 47.4% detailed 42% female, and of patients in the instructions and 39% African usual care group. demonstration of American Death occurred CONGESTIVE HEART FAILURE 25 how to use the 11/1% of the telemonitoring telemonitoring system. The group and 11.4% telemonitoring in the usual care was performed group. No using a adverse events commercial were reported. system, TelAssurance which was selected on the basis of technical quality. The telemonitoring group was instructed to make daily calls and answer a series of questions about their general health and heart failure CONGESTIVE HEART FAILURE 26 symptoms. Curtis, A. B., The study Worley, S. J., Randomization Of the 918 The study compared patients enrolled concluded Adamson, P. B., biventricular 698 were biventricular Chung, E. S., pacing to randomly chosen pacing was Niazi, I., conventional n=349 were superior to Sherfesee, L.,… right ventricular assigned conventional Suttong, M. pacing in patients biventricular right ventricular (2013). with pacing and pacing in patients atrioventricular n=342 were with AV block (AV) block and assigned right and left left ventricular ventricular ventricular systolic pacing. Patients systolic dysfunction. The with indications dysfunction with study is called for pacing with NYHA class I, the BLOCK HF AV block; II, or III heart trial and funded NYHA class I, failure. Patients by Medtronic. II, or III failure; receiving and left biventricular ventricular pacing had lower ejection fraction incidence of of 50% or less. heart failure, death from any CONGESTIVE HEART FAILURE 27 cause, and progression of heart failure as measured by left ventricular endsystolic volume index. El-Refai, M., This was a 1,835 patients BB exposure Peterson, E. L., retrospective study met the inclusion was associated Wells, K., Swadia, of insured patients criteria and made with a similar T., Sabbah, H. N., who were up the study protective effect Spertus, J. A.,… hospitalized for cohort. regarding time Lanfear, D. E. HF from January to death or (2013). 2000 to June hospitalization 2008. in HF patients regardless of whether EF was preserved or reduced. Felker, G. M., Lee, This study The DOSE study A total of 308 Patients K. L., Bull, D. A., compared the was a prospective, patients were assigned to the Redfield, D. A., administration randomized, enrolled between high-dose CONGESTIVE HEART FAILURE 28 Stevenson, L. W., of furosemide double-blind, March 2008 and furosemide Goldsmith, S. R., intravenously controlled trial November 2009. therapy were … O'Connor, C. by means of conducted by the The mean age of more likely to M. (2011). either a bolus Heart Failure the patients was change to oral every 12 hours Clinical Research 66 years, 27% diuretics within or continuous Network and was women, and 25% 48 hours. High- infusion and at funded by the African dose furosemide either low dose National Heart, American. The resulted in (equivalent to Lung, and Blood mean ejection greater net fluid the patient’s Institute. The trial fraction was loss, weight loss, previous oral used a 2-by-2 35%, 74% were and decrease in dose) or high factorial design hospitalized symptoms. dose (2.5 times and randomly within the Patients in the the oral dose) previous 12 low-dose group in patients with 1:1:1:1 ratio. months for heart were more likely acute failure with to require 50% decompensated moderate renal increase in the heart failure. dysfunction dose within 48 (mean serum hours (24% creatinine level compared to 1.5 mg/dl. 9%). There were assigned, in a no differences between the CONGESTIVE HEART FAILURE 29 bolus group and the continuous infusion group. There were more cases of ventricular tachycardia in the bolus group and more cases of renal failure in the continuous infusion group.The median length of hospitalization was 5 days and did not change across the Fu, M., Zhou, J., Meta Analysis of A total of 2554 The present Sun, A., Zhang, S., 7 prospective patients (mean study Zhang, C., studies age: 75.1 years, demonstrated female: 58%) that ACE Yunzeng, A.,… CONGESTIVE HEART FAILURE Ge, J. (2012). 30 were recruited inhibitors as with an average monotherapy or follow up of 20.9 first-line therapy months. resulted in a significant reduction in allcause mortality in HFPEF. In addition, ACE inhibitors reduced heart failure related rehospitalization in a HEPEF subgroup aged > 75 or treatment over a period of 21 months. Galin, I., & Baran, D.A. (2003, September). Goodlin, S.J. (2009). CONGESTIVE HEART FAILURE 31 Gjesdal, K., Feyzi, Patients were The results randomized to 7329 patients with AF at moderate- J., & Olsson, S. B. (2008). preventive to-high risk digitalis, like suggest that ireatment of other thromboembolism, Inotropic drugs, either with may increase warfarin or the mortality. This oral direct may be thrombin inhibitor Concealed in ximelagatran. The heart failure, but survival of users be revealed in and non-users of Patients with digitalis was AF, who need investigated. the rate-reducing effect of digitalis, but do not benefit much from an increased inotropy. Homma, S., The WARCEF The study was The study The study Thompson, J. L., trial was conducted using a followed 2305 concluded there CONGESTIVE HEART FAILURE 32 Pullicino, P. M., completed to cooperative, patients for up to was no Freudenberger, R. compare the double-blind, six years. significant S., Teerlink, J. R., efficacy of multicenter trial at Eligible patients overall Ammon, S. E., warfarin (with 168 centers in 11 were at least 18 difference in the …Buchsbaum, R. a target ratio of countries years old with primary (2012). 2.0 to 3.5) and sponsored by the normal sinus outcome aspirin (at a National Institute rhythm, no between the dose of 325 of Health. contraindications treatment with mg) in patients to warfarin warfarin and the with heart therapy, and an treatment with failure and LVEF of 35% or aspirin. There sinus rhythm. less. Patients was a reduced with a clear risk of ischemic indication for stroke in the warfarin or warfarin group aspirin were but this was excluded. The offset by an mean LVEF was increased risk of 24.7+/- 7.5% major with no intracerebral significant hemorrhage. The difference study concluded between the that the choice CONGESTIVE HEART FAILURE 33 warfarin and the between aspirin groups. warfarin and aspirin should be individualized. Lindenfield, J., c Albert, N.M., Boehmer, J.P., Collins, S.P., Ezekowitz, J.A., Givertz, M.M., … Klapholz, M. (2010, June). McMurray, J. This article The Tests and Possible V. (2010). discusses information is Findings with evidence-based based on Recommendations: pharmacologic randomized, Electrocardiography treatment of heart controlled : Control atrial failure using trials involving fibrillation or flutter ACEI, beta- patients with and consider blockers, ARBs, chronic heart anticoagulation, aldosterone failure or with consider cardiac CONGESTIVE HEART FAILURE 34 blockers, and heart failure, resynchronization. hydralazine. The left ventricular Administer beta- article discusses systolic blockers with possible findings dysfunction or caution for sinus in patients with both. bradycardia. left ventricular Chest radiography: systolic Administer adequate dysfunction and diuretics for recommended pulmonary treatment congestion, edema, including or pleural effusion. lifestyle and Hematologic tests: exercise, perform a diagnostic implantable workup and treat devices, cardiac- iron deficiency. resynchronizatio Increased creatinine: n therapy, administer RAAS coronary blocker with revascularization, caution. and cardiac Hypokalemia: add transplantation. or increase the dose of RAAS blocker, consider potassium CONGESTIVE HEART FAILURE 35 replacement. Hyperkalemia: stop potassium replacements, reduce dose or withdraw RAAS blocker. Hypnonatremia: reduce or discontinue use of thiazide diuretic; reduce water intake; consider treatment with tolvaptan if severe. Hyperuricemia: consider reducing diuretic dose as much as possible, administer prophylaxis for gout. ACEI Dosing CONGESTIVE HEART FAILURE 36 Captopril starting dose 6.25mg 3 doses daily with target dose of 150mg/daily. Enalapril starting dose 2.5mg twice daily with target dose 20-40mg daily. Lisinopril starting dose 2.5-5mg daily with target dose of 20-35mg daily. Ramipril starting dose 2.5mg 1-2 doses with target dose 10mg/daily. Beta-blocker dosing Bisoprolol 1.25mg daily with 10mg/daily target. Carvedilol 3.125mg twice a day with CONGESTIVE HEART FAILURE 37 target dose 50100mg/daily. Metoprolol XL 12.5mg-25mgdaily with target dose 200mg daily. Angiotensionreceptor blockers dosing Candesartan 4 mg daily with target dose 32 mg daily, Valsartan 40mg twice a day with target dose 320mg/daily. Losartan 50mg daily with target dose 150 mg/daily. Aldosterone blockers: Should be initiated to patients who CONGESTIVE HEART FAILURE 38 remain NYHA class III or IV despite treatment with diuretic, and ACEI or ARB, and a betablocker. Eplerenone 25 mg daily with target dose 50mg/daily. Spironolactone 25 mg daily with target dose 25-50mg/daily. Hydralazineisosorbide dinitrate Hydralazine 37.5mg three times a day with target dose being 225mg/daily. Isosorbide dinitrate 20mg three times a day with target dose 120mg/daily. CONGESTIVE HEART FAILURE 39 Lifestyle modification tailored structured aerobic exercise improved functional capacity and quality of life. Implantable Cardioverter Defibrillators reduces risk of sudden death in patients with left ventricular systolic dysfunction. Indicated for patients who survive unprovoked ventricular fibrillation or sustained CONGESTIVE HEART FAILURE 40 tachycardia and for primary prevention in patients with NYHA functional class II or III who have an ejection fraction persistently 35% or less despite optimal medical management and expected to survive greater than one year. Cardiac transplantation is last resort for refractory heart failure. Mujib, M., A retrospective 4189 Patients Those discharge Patel, K., study of the were chosen with the initiation of Fonarow, G. C., Organized from the 10,570 an ACE inhibitor Kitzman, D. Program to patients aged >65 upon discharge from W., Zhang, Y., Initiate years with heart the hospital with a CONGESTIVE HEART FAILURE 41 Aban, I. Livesaving failure and diagnoses of heart B.,….Ahmed, Treatment in preserved failure with a A. (2013). Hospitalized ejection fraction preserved ejection Patients with in the Organized fraction showed a Heart Failure Program to modest (2003-2004) Initiate improvement in the Lifesaving end point of total Treatment in mortality or heart Hospitalized failure hospitalizion. Patients with Heart Failure linked to Medicare Patel, K., A retrospective 3806 Patients ARB’s were not Fonarow, G. C., study of the were chosen associated with Kitzman, D. Organized from the 10,570 improved clinical W., Aban, I. B., Program to patients aged >65 outcomes. Love, T. W., Initiate years with heart Allman, R. M., Livesaving failure and … Ahmed, A. Treatment in preserved (2012). Hospitalized ejection fraction Patients with in the Organized Heart Failure Program to CONGESTIVE HEART FAILURE 42 (2003-2004) Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure linked to Medicare Ruschitzka, F., This study was The study was The study The study concluded Abraham, W. conducted to conducted involved 115 that T., Singh, J. P., determine if using a centers in resynchronization in Bax, J. J., cardiac- randomized patients with patients with in this Borer, J. S., resynchronizatio trial. NYHA class III category had Brugada, J.,… n therapy (CRT) or IV heart increased mortality Holzmeister, J. improved failure, a LVEF and the study was (2013). morbidity and of 35% or less, a stopped. There were mortality in QRS duration of 45 deaths in the chronic systolic less than 130 CRT group and 26 heart failure with msec, and in the control group. a wide QRS evidence of left complex. ventricular dyssynchrony on echocardiogram. CONGESTIVE HEART FAILURE 43 At study end 809 patients had undergone resynchronizatio n and the study was aborted due to futility and increased mortality. Taylor, A. L., Ziesche, S., Yancy, C., Carson, P., D'Agostino, R., Ferdinand, & Kohn, J. N. (2004). Velazquez, E.J., This study was The study A total number There was no Lee, K.L., Deja, conducted to utilized a of 2136 patients significant M.A., Jain, A., determine the randomized were involved in difference with Sopka, G., role of coronary- trial. Patients the study respect to the Marchenko, A., artery bypass were between July primary end point of …Ali, I.S., grafting (CABG) randomized to 2002 and May death. Patients CONGESTIVE HEART FAILURE (2011, April). 44 to treat patients either receive 2007 in 99 assigned to CABG with coronary medical centers in 22 and medical artery disease management countries. The treatment had lower and heart failure. alone or patients had a rates of death from The study is medical LVEF less than cardiovascular referred to as the management 35% and causes and of death Surgical plus CABG. coronary artery from any cause or Treatment for disease hospitalization for Ischemic Heart amendable by cardiovascular Failure (STICH) CABG. The causes. and was funded median age of by the NHLBI in the patients was conjunction with 59. Abbott Laboratories. Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., …Wilkoff, B. L. (2013). The American Heart Association (AHA) and American College of Cardiology (ACC) 20013 guidelines make the following recommendations for the management of chronic heart failure in the adult: The The AHA/ACC AHA/ACC guidelines were guidelines developed based were on data from developed clinical trials through about the collaboration usefulness and with the efficacy in N/A CONGESTIVE HEART FAILURE 1. Control Hypertensionboth systolic and diastolic hypertension, treat lipid disorders, and manage diabetes according to guidelines. 2. Patients should be counseled on lifestyle modifications. 3. Ventricular rate should be controlled or sinus rhythm should be restored. 4. Thyroid disorders should be treated according to guidelines. 5. ACEI and beta-blocker 6. Patients with known atherosclerotic disease should be managed to prevent secondary complications. 7. An ARB should be used if intolerant to ACEI. 8. Coronary revascularization or valve replacement repair if needed. 9. AICD in patients with 45 American different College of populations. Physicians and the International Society for Heart and Lung Transplantatio n and endorsed by the Heart Rhythm Society. CONGESTIVE HEART FAILURE ischemic cardiomyopathy 40 days post-MI if LVEF is 30% or less, are NYHA class I on chronic optimal medical therapy and expected to survive for at least one year. 10. Digoxin should not be used in patients with low LVEF, sinus rhythm and no history of heart failure symptoms. 11. Calcium channel blockers with negative inotropic effects may be harmful. 12. Diuretics and fluid restrictions 13. NSAIDS and other drugs known to adversely affect heart failure and reduce LVEF should be discontinued. 14. Immunization to prevent pneumonia and influenza. 15. Aldosterone Antagonists 16. Exercise Training 17. Intermittent intravenous 46 CONGESTIVE HEART FAILURE positive inotropic 47