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Heart failure (HF) is a syndrome of reduced cardiac output (CO) compromising the metabolic needs of bodily organs and tissues. Heart failure may result from dilation of the left ventricle and a subsequent reduction in left ventricular function (dilated cardiomyopathy or systolic dysfunction). Alternatively, HF may result from hypertrophy and subsequent underfilling of the left ventricle (hypertrophic cardiomyopathy, diastolic dysfunction, or HF with preserved ejection fraction). Progressive HF often severely limits exercise capacity, and mortality is most commonly associated with sudden cardiac death (SCD) or pump failure. Chronic HF may be managed with lifestyle modifications, medications, and implantable devices to delay progression and reduce mortality. Medical management aims at disrupting the neurohormonal pathways that are associated with the disease. Key targets include the sympathetic nervous system (SNS) and the renin angiotensin aldosterone (RAA) system.1,2


Approximately 5 million people in the United States are living with this disease and roughly 550,000 new diagnoses are made annually. After the age of 65, approximately 10 out of every 1000 people will be diagnosed and the numbers have steadily risen each year.1 Although HF due to systolic dysfunction is the most well-recognized diagnosis, approximately 50% of cases are due to diastolic dysfunction. The majority of studies determining appropriate medical management of HF have been conducted in patients with systolic dysfunction, and thus, the discussion of drug therapy in this chapter will focus on that literature. Hospitalization rates for HF continue to rise and are its primary expense. In addition to hospital admissions and morbidity, HF causes significant mortality with an overall 50% 5-year mortality rate.


Disease severity is determined by evaluating functional capacity or structural heart changes. The New York Heart Association (NYHA) uses exercise tolerance and ability to perform activities of daily living. Patients may be classified as NYHA class I if there are no symptoms or restrictions in activity, class II or III if there are symptoms with moderate or mild physical activity, respectively, and class IV if symptoms are present at rest. The NYHA classification system allows a patient's current state of HF health to be assessed at a particular point in time. A patient may shift between classes as disease control improves or declines.3 To classify patients in a sequential manner as the disease state progresses, the ACC/AHA developed a staging system based on risk factors for HF and structural determinants. Using this system, patients are categorized as being at risk of developing HF (stage A), having structural heart disease but no symptoms (stage B), developing HF signs and symptoms (stage C), and having end-stage disease despite maximal medical therapy (stage D).1

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Key Definitions
ACC = American College of Cardiology
AHA = American Heart Association
CO = cardiac output
SV = stroke volume
HR = heart rate
BSA = body surface area
EF = ejection fraction
LVEDP = left ventricular end ...

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