Cardiovascular changes occur in elderly individuals even without overt disease.1 Aging dramatically affects the myocardium and cardiac valves; vasculature, the autonomic nervous system, and impulse formation and propagation also undergo measured change with functional consequences.1 One example of this concept is the tendency for enlargement of the left atrium in advancing age to increase the likelihood that atrial fibrillation will develop.1 This column will address age-related changes in cardiac valves, with a focus on aortic valvular stenosis.
Aortic stenosis refers to abnormal orifice narrowing of the aortic valve causing obstruction of blood flow from the left ventricle to the ascending aorta during systole.2,3 In the elderly, etiologies for aortic stenosis include calcification of a normal tricuspid aortic valve, calcification of a congenital bicuspid valve, and rheumatic valve disease.4 Calcification of a tricuspid valve is the cause of aortic stenosis in 90% of patients older than 65 years.4 While causes of calcification are unclear, there are similarities to atherosclerosis with regard to process; a discussion of this relationship can be found under Risk Factors, below.
Forms of Aortic Stenosis
Different forms of aortic stenosis can be distinguished on a clinical basis by age at onset and characteristic echocardiographic findings.3 Calcific aortic stenosis (referred to as “degenerative” or “senile type”) affects trileaflet aortic valves, frequently in patients with other risk factors for atherosclerotic disease.5 This form of aortic stenosis is associated with slow disease progression and presentation in patients between the ages of 70 and 90 years.3 Further, this disease is an active process involving deposition of lipids, inflammation, and calcification; fibrosis and calcification of the aortic valve result in valvular stiffening and dysfunction.1 Currently, senile degenerative aortic stenosis is the leading indication for aortic valve replacement.6 Adult patients with congenital bicuspid aortic valves frequently have known of a heart murmur for several years with an onset of symptoms between the ages of 40 and 60 years; this condition occurs predominantly in men.7 Congenital aortic stenosis usually presents in childhood (unicuspid or bicuspid valve); rheumatic disease, homozygous hypercholesterolemia, and radiation heart disease are considered other less common causes of aortic stenosis.3
There are similarities in histopathology between atherosclerosis and aortic stenosis--risk factors are similar, including lipoprotein deposits, active inflammation, and calcification of the valve.2,4 For an extensive list of risk factors for atherosclerosis, including modifiable, nonmodifiable-established, and nonmodifiable-nonestablished, refer to online Reference 8. Aortic sclerosis is defined as aortic valve thickening; that is, calcium accumulates but thickening does not obstruct blood flow through the valve.9,10 Aortic sclerosis, associated with male gender, hypertension, smoking, diabetes mellitus, and lipid abnormalities, is present in 25% of patients older than 65 years and 48% of patients older than 75 years.4 It may cause a soft heart murmur, but does not cause symptoms.9 Sclerosis progresses to stenosis; since aortic stenosis can progress slowly or in some cases quickly, regular follow-up is required to detect progression of disease (via echocardiography).2 This is especially important in sedentary seniors in whom blood flow may be significantly compromised without causing symptoms.2
While data indicates that aortic sclerosis appears to increase the risk of myocardial infarction (by 40%), it may also increase the risk of angina, heart failure, and stroke.2 It is theorized that the reason for this may be progression from aortic sclerosis to aortic stenosis, or may be comorbid dyslipidemia, underlying inflammation (local or systemic), or endothelial dysfunction causing sclerosis and coronary artery disease.2
Symptoms, Signs, and Complications
Symptom Triad: There are no visible signs of aortic stenosis.2 Regardless of the form, progressive untreated disease will ultimately result in angina (commonly precipitated by exertion), syncope (on exertion or at rest), and heart failure; exertional dyspnea is the most common complaint.2,6 Manifestation of these symptoms most commonly occurs after age 60 years.6 Complications of aortic stenosis may include infective endocarditis and arrhythmias, including ventricular fibrillation leading to sudden death.2,6 In cases of mild or moderate aortic stenosis, systolic blood pressure may be high; it falls as the condition becomes more severe.2 The hallmark finding is a crescendo-decrescendo ejection murmur heard with a stethoscope when a patient who is sitting upright leans forward; the murmur changes as the disease progresses (a thorough description of these murmur changes may be found in online Reference 6).6
Left Ventricular Hypertrophy and Heart Failure: More than 500,000 hospital admissions per year for congestive heart failure occur in senior patients 65 years or older.1 Any disorder that affects the ability of the heart to contract (systolic dysfunction) and/or relax (diastolic dysfunction) can cause heart failure.11 Heart failure develops in approximately 50% of elderly patients with severe aortic stenosis.12 Aortic stenosis can con-tribute to pressure overload causing compensatory left ventricular hypertrophy--a cause of systolic dysfunction detectable on both echocardiogram and electrocardiogram--which can result in heart failure.4,11,13 In particular, female geriatric patients are prone to the development of excessive ventricular hypertrophy.4 Left ventricular hypertrophy secondary to aortic stenosis, as well as age-related changes, both promote diastolic dysfunction, rendering the geriatric patient with aortic stenosis more dependent on contraction of the atrium for filling the ventricle.4
Diagnosis of aortic stenosis is suspected on physical examination (abnormal heart sounds, abnormalities in the pulse) and confirmed by echocardiography.2,9 (For a detailed description of the history, physical examination, differential diagnosis, and workup, refer to online Reference 6). Of note, diagnosis of congestive heart failure in elderly individuals can be difficult since it often presents only as anxiety, altered mental status, dyspnea, abdominal discomfort, or sleep disturbance.1
Primarily, the management of patients with symptomatic aortic valvular stenosis is interventional.6 Medication therapy is reserved for patients who experience complications of aortic stenosis such as heart failure, infective endocarditis, hypertension, or arrhythmias.6
Symptomatic aortic stenosis is treated by valve replacement.2 For example, in symptomatic patients with pressure-overload hypertrophy caused by aortic stenosis, aortic valve replacement should be performed.14 The American Heart Association endorses this methodology by stating that “patients who develop symptoms require surgery, not medical therapy”; however, individual risks and benefits should be used as a basis for assessment of surgical candidacy for valve replacement.4 In the geriatric patient, preoperative evaluation for coronary artery disease (cardiac catheterization) is performed so that coronary artery bypass graft (CABG) surgery and valve replacement can be performed at the same time, if indicated.2,9
If the patient with aortic stenosis is asymptomatic or not a candidate for surgery, medication management should be considered; this is the case even though there is no basis with regard to survival advantage (refer to Prognosis section below).4 Any treatment other than surgery is generally considered palliative care since there is no documented treatment currently available that will definitively delay or reverse aortic valvular stenosis.4 The possible impact of secondary prevention measures to reduce the progression of aortic stenosis has been investigated, particularly regarding lipid lowering with statins.2,15,16 Several small observational studies have suggested that HMG-CoA reductase inhibitor (statin) use can reduce aortic valve leaflet calcification and delay the progression of aortic stenosis severity.17
Asymptomatic patients should be instructed to report the development of the following: chest pain, tightening, or pressure; dizziness, lightheadedness, or syncope; and any sign of congestive heart failure (e.g., exertional shortness of breath, orthopnea, dependent edema, fatigue, exercise intolerance).4,18 When intervention is not an option for a patient with signs of heart failure, inotropic therapy (digoxin), diuretics, and nitrates should be utilized.6 Further, in the case of congestive heart failure in the very old, it may be appropriate for the primary health care provider to broach the subject of end-of-life care planning with the patient and caregivers, if it has not already been addressed.1
McPherson notes that digoxin can be used as an inotropic agent and diuretics may be used for pulmonary congestive symptoms; both categories of agents should be used with extreme caution to avoid a critical reduction in preload (left ventricular filling) or systemic arterial blood pressure in patients with significant aortic stenosis.6 Afterload reducers, such as ACE inhibitors, have the potential to cause detrimental hypotension and decrease coronary artery perfusion.2 Patients with atrial fibrillation are treated with digoxin to control the ventricular rate.6
For angina, nitrates are a treatment option; however, rapid-acting forms can precipitate orthostatic hypotension and (rarely) syncope owing to an inability of the obstructed ventricle to compensate for a rapid decrease in blood pressure.2 Vasodilators may be used for heart failure and for hypertension.6 To avoid additional increase in vascular afterload, severe hypertension, frequently seen in the elderly patient with aortic stenosis, should be treated.6 While it is advisable to reduce blood pressure to normal levels (according to Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines), hypotension must be avoided.19 In patients with decompensated heart failure in the hours before valve replacement, nitroprusside has been used as a temporary measure to reduce afterload; however, caution and monitoring are advised since this agent has the same effect as rapid-acting nitrates.2
Antibiotic prophylaxis for the prevention of bacterial endocarditis is no longer recommended in patients with aortic valvular stenosis (see Reference 20).6,20,21 In younger patients with mild valvular deformity, the risk of infective endocarditis is higher as compared with older patients with degenerative calcified aortic valves, although it can occur in the geriatric patient population.6 Hospital-acquired Staphylococcus aureus bacteremia can occur at any age and is often seen as a consequence of aortic valve replacement.6
Sudden death, while occurring in 3% to 5% of patients with aortic stenosis, is rarely seen in asymptomatic patients.4 However, since progression of this condition is so gradual and major symptoms overlap with other changes attributed to aging, its severity is often underestimated; this unfortunate scenario frequently propels the elderly into the symptomatic phase undetected.4 Without valve replacement, angina is associated with a 50% 5-year mortality, syncope is associated with a 50% 3-year mortality, and heart failure is associated with a 50% 2-year mortality.
There is a favorable long-term outcome following aortic valve surgery and relatively low operative risk.6 This should be considered in light of the prognosis of congestive heart failure in the very old as worse than the prognosis of most cancers (<20% 5-year survival rate).1
Role of the Pharmacist
Polypharmacy is considered a special therapeutic issue in the elderly. Pharmacists should be vigilant in monitoring for medications that patients may deem insignificant or benign, but may actually exacerbate congestive heart failure (e.g., NSAIDs). Additionally, pharmacists need to pay particular attention to the potential for drug interactions and the need for renal or hepatic dosing adjustments in patients with complex multi-medication drug regimens that are standard in the treatment of congestive heart failure.
Since aortic sclerosis and aortic stenosis are often asymptomatic, pharmacists in various practice settings have an opportunity to recognize early symptoms and also guide patients to have newly manifested symptoms evaluated to facilitate early diagnosis and intervention. After valve replacement surgery, pharmacists play an important role in monitoring patients on anticoagulation therapy and those receiving antibiotic prophylaxis for the prevention of bacterial endocarditis.
Major symptoms of aortic stenosis overlap with age-related changes in seniors, causing the severity and high mortality of aortic stenosis to be frequently underestimated. Furthermore, despite the presence of severe left ventricular outflow obstruction, patients with severe aortic stenosis may be asymptomatic for many years. The importance of accurate and timely diagnosis and intervention in this condition should be recognized and emphasized by pharmacists. Additionally, pharmacists play a key role in the monitoring of medication for those individuals with associated heart failure.
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