The less familiar side of heart failure: Symptomatic diastolic dysfunction

Control of volume status

Diuretics. It has long been recognized that diuretics are a useful and necessary adjunct in the management of volume overload in patients with heart failure⁴²; however, no large, long-term studies are available to evaluate the effects of these medications on mortality.⁴³ Without concurrent ACE inhibitor/ARB and beta-blocker therapy, diuretics have been shown to cause rebound sympathetic activation.^44,45

For patients with either systolic or diastolic dysfunction, diuretics may be dosed aggressively to achieve euvolemia. But for patients with DHF who are partly dependent on volume coupled with increased heart rate to maintain cardiac output, excessive diuresis can cause a significant reduction in preload, which can worsen symptoms.^20,22,30 It is advocated that long-term diuretics should be used judiciously in the treatment of both SHF and DHF, with individualized, tailored therapy being preferred and daily weights used as a guide to determine optimum fluid status.⁹

Medications to control heart rate

Beta-blockers. In addition to their anti-hypertensive effects, beta-blockers may also be used as rate-lowering therapy in the treatment of DHF. Dosing and titration in this setting are handled differently than for SHF. Whereas titration of beta-blockers in SHF requires careful adjustment to avoid worsening of the patients’ symptoms and subsequent exacerbation,^46-48 dosing in DHF can be more aggressive, with a resting heart rate goal of 60 to 70 bpm.^20,49 Beta-blockers are used as negative chronotropes in this instance to improve left ventricular filling. Beta-blockers are also useful in the management of ischemia and angina associated with diastolic heart failure.^19,20

Calcium channel blockers. For patients with contraindications to beta-blocker therapy, non-dihydropyridine calcium channel blockers (verapamil, diltiazem) may be employed as rate-lowering therapy for DHF.¹⁹ Unlike the other drugs used in DHF, non-dihydropyridine calcium channel blockers have no role in the treatment of SHF except in the presence of tachyarrhythmias.²⁰

Dihyropyridine calcium channel blockers (ie, amlodipine, felodipine) should be reserved for heart failure patients in general with angina refractory to beta-blockers. Amlodipine and felodipine are probably the safest of the dihydropyridine calcium channel blockers to use for the treatment of angina as they have not been shown to worsen existing SHF.^50,51 Verapamil has been shown in a small study to increase exercise capacity and heart failure score in patients with DHF.⁵²

Digitalis. The use of digoxin in patients with DHF was evaluated in the Digitalis Investigation Group (DIG) ancillary trial, a parallel substudy of the overall DIG Trial that enrolled 988 patients with diastolic dysfunction.³⁹ DHF patients receiving digoxin were found to have fewer symptoms and hospitalizations, although this finding was not statistically significant. These findings should be weighed against recent data suggesting that digoxin predisposes women with depressed left ventricular systolic dysfunction to an increased risk of death.⁵³ The role of digoxin in DHF is unclear, and it is recommended that its use be restricted to patients with recurrent hospitalizations and refractory tachyarrhythmias despite optimized medical therapy.^9,20,30,54

Prognosis

The annual mortality of patients with DHF has been reported as 5% to 8%, whereas mortality associated with SHF approximates 10% to 15%. However, in patients aged >70 years, both SHF and DHF have a 5-year mortality of 50% and both have an estimated 50% annual hospital admission rate.⁵⁸

Looking forward

Greater recognition of the disorder and more enrollment of patients with DHF in outcome-based studies will hopefully improve our understanding and approach to treatment of this specific form of heart failure.^40,55

Ongoing studies that may provide more evidence-based data to guide therapy for DHF include the Irbesartan in Heart Failure with Preserved Systolic Function Trial (I-PRESERVE), Perindopril for Elderly People with Chronic Heart Failure Study (PEP-CHF) and Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS).^56-58

Acknowledgments

The authors wish to thank Thomas Hill and JoAnn Moates for their invaluable research assistance in preparation of this manuscript.

CORRESPONDING AUTHOR
Spencer A. Morris, PharmD, BCPS, Georgetown Hospital System, Georgetown Memorial Hospital, 606 Black River Road, Georgetown, SC 29440. E-mail: spenceamorris@aol.com.