Medication
Initial dosage
Titration
Target dosage
Angiotensin-converting enzyme inhibitor
Lisinopril [3]
5 mg daily
Double every 4 weeks
20–40 mg daily
2.5–5 mg BID
Double every 1–2 weeks
10–20 mg BID
Ramipril [22]
1.25 mg daily
Double every 2 weeks
1.25–10 mg daily
12.5 mg BID or TID
Double every 4 weeks
25 mg BID–50 mg TID
Quinapril [5]
10 mg daily
Double after 4 weeks
20 mg daily
Angiotensin receptor blocker
Valsartan [8]
40 mg BID
Double every 2 weeks
160 mg BID
Candesartan [9]
4–8 mg daily
Double every 2 weeks
32 mg daily
In the case of persistent hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90) after up-titrating ACE inhibitors or ARBs, additional antihypertensive medications should be considered to achieve reduction in blood pressure, with the exception of nonvasoselective calcium channel blockers which should be avoided [23]. In the setting of advancing heart failure class, care must be made to exchange medications that were used for blood pressure control with ones that reduce morbidity and mortality in this population.
Stage B Management: Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker, Beta-Blocker, and Implantable Cardiac Defibrillator
The main goal of drug therapy in stage B patients is attenuation and/or reversal of adverse cardiac remodeling by aggressive inhibition of neurohormonal axes, specifically the sympathetic and renin–angiotensin and aldosterone systems. This is accomplished by initiation and titration of an ACE inhibitor or angiotensin receptor blocker followed by one of the three different beta-blocker options, carvedilol, bisoprolol, or metoprolol succinate, all of which have demonstrated incremental survival benefit when added to an ACE inhibitor or ARB [10–13]. The target dose of ACE inhibitor or ARB that should be reached prior to addition of a beta-blocker is debatable. However, dose-dependent incremental survival benefit has been more clearly demonstrated with beta-blockers than with ACE inhibitors, the latter of which impact survival significantly even when used at minimal doses [24, 25] In light of this, a commonly recommended strategy is to start an ACE inhibitor or ARB at a low to moderate dose, after which the focus shifts to initiation and titration of a heart failure-specific beta-blocker to either target or maximum tolerated dose. Titration of these medications should generally be made at 2-week intervals, holding dose titration in the setting of symptomatic hypotension or bradycardia (heart rate <60 beats/min, untreated second- or third-degree atrioventricular block) [10]. During titration of beta-blockade, systolic blood pressures in the 90–100 mmHg range may occur and should not cause alarm in the absence of near syncope or syncope (see Table 19.2).
Table 19.2
Titration of beta-blockers
Medication | Initial dosage | Titration | Target dosage | Special considerations |
|---|---|---|---|---|
Beta-blocker | ||||
Carvedilol [10] | 3.125 mg BID | Double every 2 weeks | 25 mg BID | Increased vasodilation and BP control, improved insulin sensitivity |
Metoprolol succinate [13] | 12.5–25 mg daily | Double every 2 weeks | 200 mg daily | Less bronchospasm, less hypotension, dosed once daily |
1.25 mg daily | Increase by 1.25 mg weekly until the dose of 5 mg is reached. Then increase by 2.5 mg every 4 weeks | 5–10 mg daily | ||
Informing patients that beta-blockers can cause initial fatigue, but that it should improve with continued use, may help with compliance. In addition, consideration of switching between agents, or administration at bedtime, may reduce symptoms of fatigue. Specific aspects of an individual patient may impact the choice of beta-blocker used (Table 19.2). Metoprolol succinate is more beta-1 selective than carvedilol, has less vasodilatory effects, and is dosed once daily and therefore may be preferred in patients prone to bronchospasm, those with marginal blood pressure, or those whose compliance is a concern. Carvedilol may be considered as the initial agent in patients with coexisting hypertension or diabetes, since it exhibits peripheral alpha-receptor blocking effects that cause vasodilation and has also been shown to improve insulin sensitivity compared to metoprolol [26]. Patients should be taught how to monitor their blood pressure and heart rate at home on a regular basis, recognize abnormal blood pressure and heart rate, and have direct telecommunication of these data to their providers. Telecommunication systems with close provider follow-up have helped improve patient outcomes, quality of life, and compliance while reducing hospitalizations [27–29]. This becomes especially important as patients advance in heart failure stage.
Stage C Management: Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker, Beta-Blocker, Aldosterone Antagonist, Hydralazine and Nitrates, Loop Diuretic, and Biventricular Implantable Cardiac Defibrillator
The stage C population is more precarious. Having close contact with the stage C patient to detect changes in NYHA class will assist in improving patient satisfaction with care and quality of life and reduce hospitalizations [27, 28]. Patients in this stage should be advised about the “rule of 2s”: (1) consume no more than 2 g of sodium daily, (2) weigh daily in the morning and double the dose of diuretic for that day if there is a weight gain of >2 lbs in 1 day, and (3) call health provider to share new information. Finally, hyponatremic patients should also institute a daily 2-L fluid restriction [1, 29–31]. Robust trials are still lacking to provide evidence to support these recommendations for sodium and fluid restriction, but they are intuitively supported guidelines that may change over time with new data from pending trials [1, 32]. A visit with a nutritionist or provider who can spend time educating heart failure patients about food labels and what products are high in sodium will also be helpful. These patients should contact their provider for complaints of new or recurrent heart failure symptoms (dyspnea, lower extremity swelling, inability to sleep lying flat) and new or recurrent angina symptoms. Structuring a clinic system to address patient complaints urgently can improve results [33].
Clinic visits should be tailored toward reaching target doses of medications, starting with ACE inhibitors or ARBs and then beta-blockers and dosing as previously described. Baseline hypotension may create reluctance to initiate or titrate these agents, all of which have antihypertensive effects. It is important to remember, however, that as long as patients do not have symptomatic hypotension and blood pressure is not profoundly reduced (i.e., systolic blood pressure <90 mmHg), those with the lowest baseline blood pressure may in fact derive the greatest benefits from therapy [34]. For the patients with NYHA functional class II–IV heart failure despite maximum tolerated doses of ACE inhibitor or ARB and beta-blocker, an aldosterone antagonist should also be initiated. Limitations to the use of aldosterone antagonists should be carefully considered, including rises in serum creatinine or potassium levels. In general, aldosterone antagonists may be initiated after the patient is on a stable dose of an ACE inhibitor, which can also affect creatinine level and cause retention of potassium. During initiation of an aldosterone antagonist, monitoring for an increase in creatinine to >2.5 mg/dL or potassium to >5 meq/L is important [1].
African-American patients may also be treated with hydralazine and isosorbide dinitrate for its morbidity and mortality benefit [18]. In non-African-American patients with persistent heart failure symptoms who do not have symptomatic hypotension, hydralazine and isosorbide dinitrate may prevent hospitalizations [35]. Patients with contraindications to ACE inhibitor or ARB should also be considered to be hydralazine and isosorbide dinitrate candidates for additional symptom control [1]. Headache and gastrointestinal intolerance occasionally prevent titration and should be monitored for when assessing compliance [1].
As the number of medications and complexity of dosing intervals increase, medical adherence can decline. Medication reconciliation at each clinic visit is helpful to confirm what medications a patient is actually taking and to explore any side effects that may adversely affect compliance. Having the patient describe how they take each medication, providing pillboxes, and addressing concerns with clinic pharmacy visits and social service consultation can also improve care [1, 36, 37].
Digoxin can be considered for patients with persistent symptoms after appropriate titration of ACE inhibitor, beta-blocker, aldosterone inhibitor, hydralazine, and nitrates. There is no mortality benefit from the use of digoxin, but it has been demonstrated to reduce hospitalizations for heart failure [16]. For patients already taking digoxin, cessation of treatment has been associated with a worsening of heart failure symptoms and clinical parameters [17]. We favor a digoxin dose no higher than 0.125 mcg daily, given that equal benefits have been observed regardless of the measured serum drug level, yet toxicities are more common at higher doses [38]. It may be preferential to use digoxin for rate control if effective rate control is not achieved with beta-blockade, rather than adding an alternate rate control medication, like verapamil or diltiazem, which could potentially worsen heart function [1] (see Table 19.3). Similarly antiarrhythmics other than amiodarone or dofetilide should be avoided in this population, given their cardiodepressant and proarrhythmic effects [1].
Table 19.3
Titration of aldosterone antagonists, digitalis, and hydralazine/nitrates
Medication | Initial dosage | Titration | Target dosage |
|---|---|---|---|
Aldosterone antagonist | |||
Spironolactone [14] | 25 mg daily | Double after 8 weeks | 25–50 mg daily |
Eplerenone [15] | 25 mg daily | Double after 4 weeks | 50 mg daily |
Digitalis | |||
Based on CrCl, age, sex, and weight | 0.625–0.250 mg daily (usually 0.125 mg sufficient) | ||
Hydralazine/nitrates | |||
Hydralazine [18] | 37.5 mg TID | Double after 2 weeksa | 75 mg TID |
Isosorbide dinitrate [18] | 20 mg TID | Double after 2 weeksa | 40 mg TID |
Diuresis
Diuresis provides symptomatic care that is usually needed to assist patients in maintaining a euvolemic state. Appropriate titration of the previously discussed medications can sometimes reduce the need for diuretics. Generally, diuretics cannot be avoided in NYHA class III–IV patients and those advancing to stage D. Loop diuretics are most effective for diuresis but have not been demonstrated to have clinical outcome benefits in and of themselves [39, 40]. Initial dosing of the loop diuretic should be determined based upon creatinine clearance and response to a trial with the patient. For lack of efficacy at one dose, the dose can be doubled until urine output is satisfactory. Initiation of furosemide may be considered as first line unless the patient has significant bowel edema or ascites that might suggest better absorption with torsemide or bumetanide [40] (see Table 19.4). However, if a patient has substantial bowel edema, IV diuretic administration may become necessary.
Table 19.4
Loop diuretic correlation table
Diuretic | Bioavailability (%) | IV-to-oral conversion | Relative potency (mg) |
|---|---|---|---|
Bumetanide | 75 | 1:1 | 1 |
Furosemide | 50 | 1:2 | 40 |
Torsemide | 80 | 1:1 | 20 |
A rise in serum creatinine can be expected while titrating diuretic therapy, but for a rise in serum creatinine of 40 % or more, diuresis should be stopped or decreased, if possible [42]. The patient should keep a record of daily morning weights to assist in regulating diuretic dosing. When the patient has signs of hypervolemia, including pulmonary edema, elevated jugular venous pressure, S3 gallop, lower extremity edema, or ascites, the provider can target diuresis toward achieving dry weight. For example, a patient who usually takes furosemide 40 mg daily could, if still urinating well on furosemide 40 mg, change regimen to furosemide 40 mg BID or TID. If they were not responding to furosemide 40 mg daily, then an increase to furosemide 80 mg daily or higher would be appropriate. While adjusting diuresis, follow-up should be obtained within a few days after each dosing change to assess for appropriateness of diuresis and electrolyte alterations. Often potassium supplementation is required if the patient is not on an aldosterone antagonist. Hypo- and hyperkalemia are associated with higher morbidity in this population. Therefore, an objective is to keep the potassium close to 4 meq/L [1]. Occasionally, additional diuretic assistance is required and can be achieved by adding the thiazide diuretic, metolazone. This should generally be reserved for inpatient use given abrupt fluctuations in circulatory response, electrolytes, and creatinine clearance that can result from the use of metolazone. Progressively worsening creatinine clearance is associated with long-term morbidity in heart failure patients. Avoidance of nephrotoxic medications should be paramount, especially NSAIDs that effectively reduce renal blood flow.
Routine chest radiography and B-type natriuretic peptide levels are not indicated in the management of congestive heart failure. Repeat structural evaluation with echocardiogram is only needed when major clinical changes have occurred that result in a change in ACC/AHA stages or NYHA functional class [1].
Implantable Cardiac Defibrillator and Biventricular Implantable Cardiac Defibrillator Therapy
There is mortality benefit from implantable cardioverter defibrillator (ICD) devices in patients with ACC/AHA stage C heart failure and persistent structural disease who are on appropriate medical therapy. It is important for the provider to monitor medication titration goals and advocate for ICD or resynchronization therapy when indicated. For primary prevention of sudden cardiac death, a mortality reduction has been demonstrated for ACC/AHA stage C patients who have persistent LVEF ≤35 % at least 40 days postmyocardial infarction, NYHA functional classes II–III, and predicted survival >1 year [1, 43, 44]. Secondary prevention ICD therapy should be provided in ACC/AHA stage C patients with a history of cardiac arrest, ventricular fibrillation, or hemodynamically unstable ventricular tachycardia [1, 45].
Resynchronization is indicated for ACC/AHA stage C patients with LVEF ≤35 %, atrial fibrillation, dyssynchrony as evidenced by QRS ≥120 ms, NYHA functional classes III–IV, and on optimal medical therapy. ACC/AHA stage C patients with LVEF ≤35 %, NYHA functional classes III–IV, on optimal medical therapy who are dependent on frequent ventricular pacing may also benefit from biventricular synchronized pacing [1, 46–48].
Stage D Management: Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker, Beta-Blocker, Aldosterone Antagonist, Hydralazine and Nitrates, Loop Diuretic, Biventricular Pacemaker, Heart Transplant, and Hospice
Evaluation of ACC/AHA stage D patients is geared toward palliation, unless heart transplant is an option. Life expectancy at this stage is greatly reduced. ICD therapy no longer provides benefit, as death is usually impending [1]. Beta-blockers can cause more harm than benefit and may need to be discontinued in the presence of symptomatic bradycardia, symptomatic hypotension, worsening fatigue, worsening dyspnea, or other signs of decompensated heart failure. ACE inhibitors, aldosterone antagonists, hydralazine and nitrates, and digoxin may still be useful if hypotension and renal function are not limiting, and effective diuresis becomes a mainstay of providing comfort. Given the high mortality among stage D patients, readdressing patient goals of care becomes very important. Options may include hospice, palliation with or without ICD deactivation, chronic inotropes, mechanical support with “bridge” or “destination therapy,” and heart transplant. Referrals to end-stage heart failure specialists can assist the provider in communicating the best care options to the patient.
Failure of Outpatient Management
Many reasons for heart failure readmission can be addressed and prevented in the outpatient setting with a good care plan. Common reasons for readmission include noncompliance with medical regimen and/or sodium and fluid restrictions, acute myocardial infarction, uncorrected high blood pressure, atrial fibrillation and other arrhythmias, addition of negative inotropic medications, pulmonary embolus, NSAID use, excessive alcohol or illicit drug use, endocrine abnormalities (diabetes mellitus, hyperthyroidism, hypothyroidism), and concurrent infections [1]. As above, a good telecommunication system and contact with providers (nurses, nurse practitioners or physician’s assistants, or physicians) can help to identify issues before outpatient management fails [27–29].
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