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17-1 ACUTE DECOMPENSATED HEART FAILURE Don’t Be Such a Busy Body . . . . . . . . . . . . . . . . . . . . . . Level II CASE SUMMARY A 64-year-old Caucasian female patient with a history of ischemic cardiomyopathy and an ejection fraction (EF) of 25% (therefore, systolic heart failure [HF]) presents to the emergency department with signs and symptoms of volume overload (weight gain, dyspnea, lower extremity edema) and a hypertensive urgency. The patient admits to medication nonadherence, which has likely contributed to disease progression, cardiac function decline, neurohormonal activation (in the absence of her β-antagonist, carvedilol, and her renin–angiotensin system antagonist, lisinopril), and volume overload due to lack of diuretic use. The patient must be diuresed as soon as possible and closely monitored to ensure efficacy and safety of her medication regimen, and the need for titration and addition of other agents must be assessed. Once the patient is adequately diuresed, special attention must be given to proper discharge education and reinforcement of the need for medication adherence. This will hopefully serve to decrease the chance of another HF exacerbation due to medication nonadherence, and reduce the likelihood of HF-associated mortality through optimization of the patient’s outpatient medication regimen. Any medications that contribute to worsening or complications of HF, particularly nonsteroidal anti-inflammatory drugs (NSAIDs) in this case, should be critically evaluated for their benefit given their risks in patients with cardiovascular disease. QUESTIONS Problem Identification 1.a. What signs and symptoms indicate the presence of ADHF in this patient? • According to the 2013 American College of Cardiology Foundation and American Heart Association (ACCF/AHA) Guidelines for the Diagnosis and Management of Heart Failure in Adults, HF diagnosis should be based mostly on signs and symptoms.1 BF complains of dyspnea and orthopnea, which have increased over the past 2–3 days, in addition to lower extremity edema and increased abdominal bloating. All of these represent symptoms of volume overload. Her PMH is significant for ischemic cardiomyopathy and an EF of 25%, which further supports her diagnosis of ADHF. 1.b. Create a list of BF’s drug-related problems, including those that may have led to ADHF. • Nonadherence to mortality- and morbidity-reducing HF medications due to her “busy schedule” has resulted in volume overload and associated congestive symptoms. • Hypertensive crisis (BP 186/92): BP may be elevated as a result of nonadherence alone, but should be monitored closely to ensure attainment of BP goals. • BF complains of dyspnea, weight gain, and lower extremity edema, all indicative of volume overload. Her CXR is significant for interstitial edema. Thus, BF should be described as “wet,” indicating a clinical finding of pulmonary congestion and elevated LV filling pressures (ie, increased preload). • BF is hypertensive, her extremities are warm, and she shows no signs of target end-organ damage; thus, she has no indications of low perfusion and should be described as “warm.” Desired Outcome 2.What are the short-term goals of pharmacotherapy regarding treatment of ADHF? • The immediate goals are to improve BF’s symptoms of volume overload and to stabilize her blood pressure. This will prevent any further organ damage. ✓Relief of the symptoms of volume overload should be achieved through the use of diuretics. Reduction in BF’s BP can likely be achieved through reinitiation of her home antihypertensives. • Additional goals of pharmacotherapy in this case include: ✓Assessment of cardiac damage and HF/CAD progression and prevention of further damage/disease progression through the use of mortality- and morbidity-decreasing medication. ✓Minimization of the utilization of healthcare resources, including reduced duration of intravenous therapy, length of hospital stay, and unplanned readmissions. Avoidance of adverse effects of medications, including electrolyte abnormalities, renal dysfunction, and hypotension. Therapeutic Alternatives 3.a. What nondrug therapies might be useful for alleviating this patient’s symptoms and preventing a recurrence of ADHF? • Oxygen therapy: Given her hypoxemia (oxygen saturation ~90%), BF should be given supplemental oxygen, most likely via nasal cannula. • Sodium and fluid restriction should be considered to improve symptom relief, along with the use of diuretics. A low-sodium diet includes a recommended maximum intake of 1500 mg daily in most hospitalized patients.1 Stricter goals may be necessary for refractory symptoms or worsening hyponatremia (eg, Na <130 mEq/L). • Assessment of the coronary arteries to detect the presence of disease through noninvasive stress testing and/or heart catheterization may be warranted, and, if indicated, coronary intervention to treat any reversible ischemia that could lead to further LV dysfunction. BF is not complaining of any chest pain, so an outpatient stress test would likely be the best option for her. • Ultrafiltration is a newer alternative approach for decreasing volume overload in patients with inadequate renal function. While the use of this approach varies by institution, it is generally reserved for patients who have very little, or no, response to all diuretic therapies. Copyright © 2017 by McGraw-Hill Education. All rights reserved. Acute Decompensated Heart Failure Kena J. Lanham, PharmD, BCPS 1.c. Which complaints and clinical findings characterize the patient’s volume status (wet or dry)? Which complaints and clinical findings characterize the patient’s perfusion status (warm or cold)? CHAPTER 17 17 • Meloxicam for osteoarthritis pain: NSAIDs are not recommended in patients with cardiovascular disease. 17-2 TABLE 17-1 Loop Diuretics SECTION 2 Bioavailability (%) Oral Dosage IV Dosage Bumetanide2 Furosemide3 80 60 Torsemide4 80 0.5–2 mg two to three times daily 20–80 mg two to three times daily (600 mg daily maximum) 5–100 mg daily (200 mg maximum) 0.5 mg initial, 10 mg daily maximum 20–80 mg two to three times daily, or continuous infusion 10–40 mg/hour (higher rates have been used, up to 160 mg/hour) NA Cardiovascular Disorders • Advanced HF treatments (eg, ventricular assist devices/ transplant): BF has no indications of inadequate perfusion given her warm and wet status. However, if her disease progresses, she may become a candidate for these advanced therapies. 3.b.What pharmacotherapeutic options are available for treatment of this patient’s ADHF? • Diuretics: ✓Loop diuretics: The 2013 ACCF/AHA guidelines recommend the immediate administration of IV loop diuretics for any patient admitted with evidence of fluid overload.1 Any of the three available agents could be used (see Table 17-1). The guidelines recommend that for patients already receiving chronic diuretic therapy, the initial dose should equal or exceed their home dose. Although diuretic use has the potential to cause renal dysfunction, hypotension, and electrolyte abnormalities and even worsen neurohormonal activation, these potential adverse drug effects should not prohibit the use of these agents. Furthermore, the doses of the loop diuretics should continue to be increased (as tolerated by the patient) in an effort to relieve congestion. If the diuretic effect is inadequate following maximum intermittent dosing, a continuous infusion may be considered.5 ✓Thiazide-type diuretics: Adding metolazone or chlorothiazide to a loop diuretic regimen blocks distal tubule sodium resorption, thereby combating rebound sodium retention at that site of action.6 Despite guideline recommendations for the addition of thiazide diuretics to enhance diuresis, no placebo-controlled studies have been performed to evaluate and measure the risks and benefits of this therapeutic approach. Therefore, thiazide-type diuretics should only be used in patients who are refractory to loop diuretic therapy alone and should be monitored closely for potential adverse effects, including severe electrolyte decreases (especially sodium, potassium, and magnesium), volume depletion, and renal dysfunction. • Intravenous vasodilators: With the exception of nesiritide, there are very few controlled trials that have evaluated the use of IV vasodilators in ADHF. Nevertheless, the 2013 ACCF/ AHA guidelines suggest that adding IV vasodilators to diuretics in patients who had inadequate response to diuretics alone can be beneficial, particularly in patients with severe volume overload and with adequate blood pressure (ie, warm/wet subset).1 ✓Nitroglycerin: Primarily a venodilator, nitroglycerin exerts its effects through decreasing pulmonary artery and left ventricular filling pressures, thus relieving pulmonary congestion and dyspnea.7 Nitroglycerin does have a dual role in reducing chest pain symptoms, so it would be beneficial if BF were complaining of chest pain. Additionally, nitroglycerin’s blood pressure–lowering effects could be utilized if the patient’s blood pressure were not adequately controlled by reinitiation of her home antihypertensives. Copyright © 2017 by McGraw-Hill Education. All rights reserved. ✓Sodium nitroprusside: The potent venodilating and arteriodilating effects of sodium nitroprusside result in significant and rapid BP reduction, which, in BF’s case, may not be needed after her home antihypertensives are reinitiated.7 Due to the potential for both rapid and significant BP reduction, the use of sodium nitroprusside should be restricted to an area with intense monitoring, such as a critical care unit. A significant concern with the use of sodium nitroprusside in a patient with renal insufficiency is the potential for accumulation of the thiocyanate metabolite, which may result in cyanide toxicity. ✓Nesiritide: Nesiritide was added to the US market in 2001 as a third vasodilator option. When compared with placebo, nesiritide effectively decreased patient dyspnea and pulmonary capillary wedge pressure in the VMAC trial.1 In the ASCEND-HF trial, nesiritide was compared with nitroglycerin in patients hospitalized for HF. Although a number of patients reported improved symptoms (44.5% vs 42.1% at 6 hours for nesiritide and nitroglycerin, respectively [P = 0.03]), the prespecified criteria for clinical significance were not met.8 Nesiritide is expensive, and both the clinical appropriateness of nesiritide as a first-line vasodilatory agent in ADHF and the cost-effectiveness of this agent are yet to be determined. Nonetheless, nesiritide remains an option in patients with complaints of dyspnea and with adequate blood pressure. • Inotropic agents: Positive inotropic agents, such as dobutamine and milrinone, provide improved hemodynamic effects by increasing cardiac index.1 Thus, there is potential benefit in patients with decreased end-organ perfusion due to cardiogenic shock, or cold symptoms. However, the risk of arrhythmias, sinus tachycardia, and increased myocardial oxygen demand, along with the potential for treatment failure, outweighs any benefit in patients without hypotension and with adequate tissue perfusion. The use of inotropic agents would not be recommended in this patient, because she has adequate blood pressure and tissue perfusion. Optimal Plan 4.What drugs, doses, schedule, and duration are best for achieving the pharmacotherapeutic goals for this patient? • BF’s congestion symptoms should be addressed as soon as possible on initial presentation. Any of the three available loop diuretics (Table 17-1) would be a valid option, but furosemide is widely used due to lower costs and physician familiarity. A general rule of thumb for a starting dose is to administer the same dose that the patient is taking at home, but in an IV form. Therefore, BF should be administered 80 mg IV twice daily and monitored for efficacy. If adequate diuresis is not achieved, as assessed through patient symptoms, urine output, and daily weights, the dose could be titrated, as tolerated, based on her vital signs, electrolytes, and renal function. Inadequate 17-3 • BF’s hypertension should be treated with a combination of the nitroglycerin infusion (which is initiated in response to not only her blood pressure but also her severe congestive symptoms) and her home antihypertensives, carvedilol 12.5 mg orally twice daily and lisinopril 20 mg orally daily. These medications not only control BF’s blood pressure but also decrease the risk of mortality in patients with LV dysfunction; thus, they should be initiated as soon as possible, and the nitroglycerin infusion discontinued as the patient’s blood pressure and symptoms allow. • A complete medication reconciliation should be performed, addressing each of BF’s outpatient medications, but paying special attention to those that have mortality- and morbidityreducing effects. Considering her elevated blood pressure and stable heart rate, carvedilol and lisinopril should be administered on admission. Additionally, BF should be assessed for possible initiation of an aldosterone antagonist, as this may provide additional mortality benefit. All other home medications, with the exception of meloxicam, should be reinitiated as well. • Meloxicam, a NSAID, is not recommended for use in patients with HF.1 The use of NSAIDs is associated with increased risk for HF exacerbations due to sodium and volume retention. BF has mild osteoarthritis, which should be treated with acetaminophen first-line, and the use of opioids and/or corticosteroid injections should be investigated if her disease progresses or if her pain is not adequately controlled with acetaminophen alone.9 Additionally, nonpharmacologic treatments, such as physical therapy, exercise, and weight loss, should be explored. Outcome Evaluation 5.What clinical and laboratory parameters are necessary to evaluate your chosen therapy for achievement of the desired therapeutic outcome and to detect or prevent adverse effects? • Diuresis: subjective assessment of patient symptoms in addition to objective assessments of urine output and daily weight monitoring should be utilized to ensure adequate diuresis and congestion relief. ✓ Assess for relief of the symptoms of volume overload at every shift. ✓Obtain urine output and weight daily to objectively measure the patient’s diuretic efficacy. ✓Electrolytes: Abnormalities are common with aggressive diuresis, so all electrolytes should be monitored at least daily. Potassium and magnesium levels should especially be optimized to decrease the risk of arrhythmias. Supplement magnesium to achieve levels above 2 mEq/L, and keep potassium levels above 4 mEq/L. Metabolic alkalosis could also occur with aggressive diuresis due to a contraction alkalosis, so closely monitor bicarbonate levels for increases. • Nitroglycerin: Assess vital signs hourly if titration is being performed; otherwise assess vitals every 6–8 hours if the infusion rate remains consistent. Monitor for symptom improvement to assess for efficacy. • HF progression: an echocardiogram should be obtained on all HF patients regularly in order to monitor disease progression. Recommend that BF have an ECHO performed on this admission since her last recorded one was over a year ago. Patient Education 6.What discharge education should be provided in order to enhance adherence, ensure successful therapy, minimize adverse effects, and prevent an unplanned readmission? • Educating patients with HF is a vital component of therapy.1 In addition to the patient, all family members and significant others should have a thorough understanding of the disease state, chronic management, and self-monitoring techniques. Complete discharge education includes the causes and prognosis of the patient’s specific condition, medication management, including specific adverse reactions and the importance of adherence, daily weight monitoring, what to do if symptoms worsen, and follow-up outpatient appointments scheduled. • No new medications will be initiated on BF on discharge, considering she was stable on her regimen until she became nonadherent to the regimen. Therefore, the components of discharge education should focus on reinforcing the importance of medication and dietary compliance and self-monitoring techniques. ✓Weigh yourself at the same time every day, preferably in the morning. If you gain more than 3 lb in 1 day or 5 lb in 3 days, you should call your designated healthcare provider. ✓Be sure to notify your healthcare provider as soon as possible if your symptoms should worsen or if new symptoms appear; these include any swelling in the legs and feet, difficulty in breathing, or chest pain. ✓You will be scheduled for a follow-up appointment within 1 week of discharge. Please be sure to keep that appointment, and be prepared to ask questions and willing to discuss any problems you may be having with your medication regimen, diet plan, or monitoring techniques. REFERENCES 1. Yancy CW, Jessup M, Bozkurt B, et al. 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 2013;128:e-240–e327. 2. Bumetanide Package Insert. Deerfield, IL, Baxter Healthcare, 2009. Copyright © 2017 by McGraw-Hill Education. All rights reserved. Acute Decompensated Heart Failure • Considering BF’s intense congestion symptoms and elevated blood pressure, an IV vasodilator could also be administered. Because of its efficacy in relieving pulmonary congestion, low adverse effect profile, and low cost, nitroglycerin should be initiated at 10 mcg/min by continuous IV infusion and titrated to achieve blood pressure goals and symptom relief. Once her oral medications are initiated and adequate diuresis is achieved, the nitroglycerin infusion should be discontinued as tolerated. ✓ Monitor vital signs, including orthostatic blood pressure and oxygen saturation, at least every shift to ensure safe titration of the chosen diuretic agent(s). CHAPTER 17 response to diuresis could be overcome through changing the dosing interval from twice-daily to three-times-daily intermittent dosing, changing to a continuous infusion, or adding a thiazide-type diuretic. Any or all of these options would be acceptable methods to induce adequate diuresis. (Note: In this case, one of these approaches is likely to be needed, considering the patient’s home furosemide dose is 160 mg per day, which is at the top of the dosing range.) Once adequate diuresis is achieved and congestive symptoms are relieved, BF should be transitioned to an oral diuretic regimen for chronic use. 17-4 SECTION 2 3. Furosemide Package Insert. Lake Forest, IL, Hospira Incorporated, 2004. 4. Torsemide Package Insert. Somerset, NJ, Meda Pharmaceuticals, 2009. 5. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 2011;364:797–805. 6. Jentzer JC, DeWald TA, Hernandez AF. Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol 2010;56:1527–1534. Cardiovascular Disorders Copyright © 2017 by McGraw-Hill Education. All rights reserved. 7. Lindenfeld JA, Albert NM, Boehmer JP, et al. HFSA 2010 comprehensive heart failure practice guidelines. J Card Fail 2010;16:e1–e194. 8. O’Connor CM, Startling RC, Hernandez AF, et al. Effect of nesiritide in patient with acute decompensated heart failure. N Engl J Med 2011;365:32–43. 9. Sinusas K. Osteoarthritis: diagnosis and treatment. Am Fam Physician 2012;85:49–56.