Digitalis glycoside. Digoxin has been shown to relieve the symptoms of HF, decrease the risk for hospitalization, and increase exercise tolerance; however, it has not been shown to offer a mortality benefit.36 Digoxin should be considered for patients who remain symptomatic when taking a diuretic and an ACE inhibitor and for patients who are also in atrial fibrillation and need rate control.
Digoxin is cleared almost entirely by the kidneys and therefore must be used with care in patients with renal dysfunction. Patients usually can be started on the expected maintenance dosage (0.125-0.25 mg/d). An oral loading dose of 0.75-1.25 mg over 24 to 48 hours can be used if an early effect is needed.9
Digoxin can induce ventricular arrhythmias (especially in a setting of hypokalemia and ischemia) and is sensitive to other medications that can drastically increase its level—most notably, amiodarone, quinidine, propafenone, and verapamil.9 The digoxin blood level should be measured every seven to 14 days until a maintenance dosage is established, and again whenever there is a change in medication or kidney function. The optimum serum level is 0.7-1.2 ng/mL; toxicity is not usually seen at < 1.8 ng/mL.9
Hydralazine and nitrates. The combination of hydralazine and isosorbide dinitrate has been shown to improve outcomes in African-American patients with HF, but efficacy is less well-established in this population than for ACE inhibitor and ARB therapy.9 This combination can be considered in patients who are unable to tolerate ACE inhibitor or ARB therapy. It can also be considered in those who have persistent symptoms despite treatment with a ß-blocker, ACE inhibitor, or aldosterone antagonist.9
Intravenous nitrates are used primarily for acute HF, especially when accompanied by hypertension or myocardial ischemia. The starting dosage for nitroglycerin is approximately 10 μcg/min, titrated upward by 10-20 μcg/min to a maximum of 200 μcg/min. Isosorbide dinitrate (20-40 mg tid) and nitroglycerine ointment 2% (1.4 in applied every six to eight hours [although generally reserved for inpatient therapy]) are equally effective.9 Adverse effects that may limit the use of these agents are headache and hypotension. Patients also develop tolerance for nitrates, which can be mitigated if a daily 8-to-12–hour nitrate-free period is instituted.9
TREATMENT OF HEART FAILURE WITH PRESERVED LVEF
Treatment options for patients with preserved LVEF (diastolic HF) are not as clear as those for patients with reduced LVEF (systolic HF). No traditional therapies (ACE inhibitors, ARBs, ß-blockers, digoxin) have been shown to improve survival in this population, although a recent study on the effects of spironolactone in diastolic HF did show some improvement of diastolic dysfunction without adverse effects.17,37 In the absense of clear evidence-based therapies, treatment focuses on managing comorbidities, addressing reversible causes, and alleviating fluid overload with a diuretic.9,17
Diuretic therapy is critical to control fluid overload; regimens are similar to those for HF with reduced LVEF. ACE inhibitors and ARBs have not been shown to improve outcomes in this population but can be used to manage comorbid hypertension. Spironolactone has also not been shown to improve outcomes in patients with diastolic HF.9
The principal conditions that can lead to HF with preserved LVEF are hypertension, pericardial disease, and atrial tachycardia. Tachycardia is associated with overall shorter diastolic filling time; controlling an accelerated heart rate, therefore, is theorized to be an important therapeutic goal.9 Other disease states, including diabetes mellitus, sleep-disordered breathing, obesity, and chronic kidney disease, can all lead to HF with preserved LVEF.
CONCLUSION
Managing HF today requires an “upstream” model of care, by which providers consider the diagnosis/syndrome of HF in the asymptomatic patient with risk factors (Stage A/Class I and Stage B/Class II). Perhaps a better way to state this is that providers must change their approach from ruling-in to ruling-out HF. Any person in whom a decrease in activity level, mild shortness of breath, or edema are observed, and who has known risk factors, should be considered to have HF until proven otherwise.
Because of the wide variability in the underlying causes of HF, providers must be dynamic in both their clinical approach and their treatment plans to optimize care for the individual patient. Finally, providers must also take note of the increasing prevalence of diastolic HF and, again, focus on early diagnosis.