Diagnosis and management of heart disease in the elderly

Figure 12.1

Probability of mortality at 30 days and 1 year as a function of age in the GUSTO-I trial (N = 41,021).





Diagnosis of myocardial infarction


In patients with acute myocardial ischemia, the electrocardiogram (ECG) often demonstrates ST-segment elevations and/or depressions, as well as T-wave abnormalities. However, older patients are less likely to exhibit diagnostic ECG changes due to preexisting conduction system disease (e.g., left bundle branch block), ventricular paced rhythm, left ventricular hypertrophy, prior MI, metabolic and electrolyte abnormalities, or medications such as digoxin or antiarrhythmic drugs.


The diagnosis of MI is confirmed when serum biomarkers of myocardial necrosis are elevated. Troponin-I and troponin-T have excellent sensitivity and specificity for diagnosing acute MI. Recently, the development of high sensitivity troponin assays has led to improved early detection of myocardial ischemia, but at the cost of a higher “false positive” rate.10 This may lead to overdiagnosis of acute MI, especially in older adults who tend to have higher ambulatory troponin levels.[11] Additionally, troponin levels may be mildly elevated in the presence of renal insufficiency, which is highly prevalent in older patients.


The high prevalence of atypical presentations and nondiagnostic ECG findings in the geriatric population requires a higher index of suspicion for acute MI in elderly subjects. Delayed diagnosis is common in older patients, reducing the “window of opportunity” for implementing appropriate treatment and limiting the extent of ischemic damage. Treatment delays also increase the risk for complications, including heart failure, arrhythmias, hypotension, myocardial rupture, and shock.


Other cardiovascular and medical conditions with similar symptom complexes should be included in the differential diagnosis for MI, especially because many of these diseases also occur more frequently in elderly individuals. Chest pain without ECG changes could signify unstable angina, but other life-threatening conditions such as pulmonary embolus, aortic dissection, acute pericardial disease, pneumonia, severe peptic ulcer disease, cholecystitis, pancreatitis, or esophageal rupture must also be considered.



Pharmacologic management of myocardial infarction


Acute MI with ST-segment elevation usually involves atherosclerotic plaque rupture and associated thrombotic occlusion of an epicardial coronary artery. However, a large proportion of infarctions in the geriatric population occur without ST-segment elevation and arise because of a mismatch between oxygen supply and demand in the setting of fixed coronary obstruction. These infarcts are designated type II MIs in the universal classification of MI schema.[12] Thus, type II MI in the elderly often occurs in association with an infection (e.g., pneumonia or sepsis), significant hypertension or hypotension, anemia, perioperative volume shifts, or other systemic illness such as thyroid disease. Therapies are directed toward improving coronary blood flow, reducing myocardial oxygen demand, reducing the risk of coronary thrombosis, correcting the precipitating illness (e.g., infection), reducing sympathetic tone, and preventing adverse remodeling of hypoperfused myocardium.


The major therapeutic options for acute MI are listed in Table 12.3. Supplemental oxygen should be administered to maintain an arterial oxygen saturation 92%. Intravenous access and telemetry monitoring are imperative to identify and treat potential complications of MI. Morphine and nitroglycerin should be administered as needed to control pain and dyspnea.



Table 12.3 Management of acute myocardial infarction




















General measures


  • Oxygen to maintain arterial saturation 92%



  • Telemetry monitoring



  • Morphine for pain and dyspnea



  • Nitroglycerin for ischemia and heart failure

Antiplatelet and antithrombotic therapy


  • Aspirin



  • Platelet P2Y12 receptor inhibitors (clopidogrel, prasugrel,* ticagrelor, cangrelor)



  • Glycoprotein IIb/IIIa inhibitors *(abciximab, eptifibatide, tirofiban)



  • Systemic parenteral anticoagulants during MI (unfractionated heparin, enoxaparin, dalteparin, bivalirudin)

Oral beta-blockers


  • (if heart rate and blood pressure are adequate)

Angiotensin-converting enzyme (ACE) inhibitors


  • (or angiotensin receptor blockers if ACE inhibitors are contraindicated)

Other disease-modifying agents


  • Eplerenone (if there is reduced left ventricular systolic function or diabetes at time of MI)



  • High-potency statins

Other medications for compelling indications only


  • Calcium channel blockers (if there is persistent hypertension; immediate-release nifedipine is contraindicated)



  • Antiarrhythmic agents (if there are refractory ventricular arrhythmias after acute MI)



  • Oral anticoagulation (select patients with anterior MI, atrial fibrillation, mechanical heart valves)

Reperfusion therapy


  • Fibrinolysis (ST-elevation or new left bundle branch block only)



  • Percutaneous coronary intervention (PCI)



  • Urgent coronary bypass surgery in selected cases

Prior to hospital discharge


  • Assessment of left ventricular systolic function (e.g., echocardiogram)



  • Tobacco cessation counseling



  • Nutritional evaluation



  • Screening for depression



  • Exercise counseling and cardiac rehabilitation referral





* Rarely indicated outside of the catheterization laboratory in patients>75 years of age


Antiplatelet therapy Aspirin 160 mg–325 mg should be administered immediately and continued indefinitely at a dose of 75 mg–162 mg daily.[13, 14] Aspirin reduces mortality in patients with unstable angina or acute MI, and the benefit of aspirin therapy increases with age, from a 1% absolute mortality reduction below age 60 to a 4.7% absolute mortality reduction at age 70 and older.[15] Clopidogrel, a P2Y12 receptor inhibitor, is a reasonable alternative (300 mg–600 mg loading dose followed by 75 mg daily) in subjects unable to take aspirin. Among patients with acute coronary syndromes, 12 months of aspirin plus clopidogrel reduces the risk of death or reinfarction by about 20% compared to aspirin alone.[16] Newer P2Y12 receptor antagonists, such as prasugrel and ticagrelor, have been associated with improved outcomes relative to clopidogrel in younger patients, but prasugrel should be avoided in patients 75 years of age due to increased risk of bleeding.[17] In contrast, ticagrelor has demonstrated improved outcomes relative to clopidogrel, including lower rates of recurrent MI and cardiovascular death, and without higher bleeding rates in elderly subjects.[18, 19] The optimal duration of dual anti-platelet therapy remains controversial, with recent studies suggesting that treatment for up to 30 months is associated with a reduction in ischemic events at a cost of increased bleeding.[20] Thus, use of prolonged dual antiplatelet therapy in the geriatric population should be individualized. Whenever possible, all of the P2Y12 agents should be withheld for five to seven days prior to elective coronary bypass or other surgery due to increased risk for perioperative bleeding. The recent U.S. approval of the intravenous P2Y12 agent cangrelor has provided an opportunity to bridge antiplatelet therapy for patients with recent MI or PCI who require urgent surgery, although its safety in older patients is not well established. An additional antiplatelet agent, vorapaxar, has been approved in the United States for add-on therapy for patients with prior MI or peripheral arterial disease, but the higher rates of bleeding and lesser benefit in elderly patients likely limit the use of this agent to very select older patients with low bleeding risk.[21]


Glycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban, abciximab) block the final common pathway of platelet aggregation and reduce infarct size in subjects with non-ST-elevation acute coronary syndromes. High-risk patients tend to gain the most benefit, particularly when undergoing percutaneous coronary intervention (PCI), but the risk of bleeding increases with age. Few studies have enrolled individuals over age 75, and one study demonstrated higher event rates in patients over age 80 receiving eptifibatide,[22] so the value of these agents in the elderly remains unclear. Due to a high risk of hemorrhage, glycoprotein IIb/IIIa inhibitors are contraindicated in patients over age 75 receiving thrombolytic therapy for ST-elevation MI,[13] and their incremental benefit in older patients receiving clopidogrel or other P2Y12 inhibitors remains unclear.


Antithrombotic therapy In patients with acute MI, unfractionated or low-molecular-weight heparin should be administered immediately in addition to the antiplatelet agents already described – particularly in patients with high-risk features such as anterior MI, large MI, associated atrial fibrillation, or recurrent ischemia.[13, 14] Low-molecular-weight heparins (e.g., enoxaparin, dalteparin) offer more predictable anticoagulation than unfractionated heparin, but these agents are almost exclusively cleared through renal mechanisms. As a result, the low-molecular-weight heparins must be used with caution given the higher rates of hemorrhagic complications with the age-associated decline in renal function. Nevertheless, the combined endpoint of death, MI, and recurrent angina is reduced,[23] with significant benefits in older subjects.[24] Low-molecular-weight heparin must be used with caution, if at all, in patients with severe renal insufficiency (creatinine clearance <30 mL/min).


Patients with large anterior MI or evidence for left ventricular thrombus should be treated with warfarin for three months after MI to maintain an international normalized ratio (INR) of 2.0–3.0. Long-term therapy with warfarin is indicated in patients with atrial fibrillation, mechanical prosthetic heart valves, or other conditions requiring systemic anticoagulation. Older patients are at increased risk for warfarin-associated bleeding complications, especially when warfarin is used in combination with aspirin or other anti-platelet agents. The utility of newer oral anticoagulants, such as dabigatran, rivaroxaban, apixaban, and edoxaban, as alternatives to warfarin in patients with recent MI has not been assessed. Among patients with indications for chronic systemic anticoagulation undergoing PCI, one study demonstrated lower rates of bleeding and similar ischemic outcomes when withholding aspirin and treating patients with clopidogrel and warfarin alone.[25] However, the number of elderly subjects enrolled was small (maximum age was 80 years), and this approach has not yet been confirmed in larger trials.


Beta blockers Beta blockers reduce mortality, recurrent ischemia, and arrhythmias in patients with acute MI.[13, 14] Contraindications include bradyarrhythmias, hypotension, moderate or severe heart failure during MI, or active bronchospasm. A history of obstructive lung disease alone should not preclude beta-blocker therapy. In a pooled analysis of several clinical trials, early treatment with beta blockers reduced mortality by 23% in older patients with acute coronary syndromes, but had no effect in younger patients.[5] In addition, long-term beta-blocker treatment after MI is associated with 6 lives saved per 100 older patients treated, versus only 2.1 lives saved per 100 younger patients. However, older patients with acute MI are also at increased risk for serious adverse events associated with beta-blocker therapy, including heart failure, hypotension, shock, and death.[26] Current guidelines recommend institution of oral metoprolol or carvedilol within 24 to 48 hours only in hemodynamically stable patients.[13] Doses should be lower and titration slower in older adults. Following MI, metoprolol, propranolol, and timolol are approved for long-term use, while carvedilol and metoprolol succinate are approved for use after MI in patients with LV ejection fractions less than 40%.


Angiotensin and aldosterone inhibition Angiotensin converting enzyme inhibitors (ACEI) reduce mortality in MI, particularly in geriatric individuals aged 65–74, and in the setting of heart failure, left ventricular (LV) dysfunction, or anterior ST-elevation MI.[27] Following MI, ACEIs reduce mortality by 17%–34% in older patients, with an absolute benefit that is three times greater than in younger individuals.[2830] Angiotensin receptor blockers (e.g., candesartan or valsartan) are suitable alternatives for ACEI-intolerant patients, but head-to-head trials have confirmed that ACEIs are the preferred medications in subjects with MI.[31] Serious potential adverse effects with both classes of drugs include hypotension, renal failure, and hyperkalemia – initiation and up-titration of these medications must be performed with caution in elderly patients with renal dysfunction or low blood pressure in the MI setting.


Eplerenone is a selective aldosterone antagonist that reduces mortality and cardiovascular hospitalizations in acute MI patients with LV systolic dysfunction (ejection fraction 40% at time of event) and either heart failure or diabetes.[32] Like spironolactone, eplerenone is a potassium-sparing diuretic that requires close monitoring of renal function and serum potassium levels during initiation and follow-up, particularly in the geriatric population.


Statins Statin therapy improves clinical outcomes after acute MI and should be initiated in all patients prior to hospital discharge.[6] The benefits of statin treatment have been verified in geriatric patients with known CAD or vascular disease,[3336] with one study demonstrating a 15% reduction in recurrent MI, stroke, or cardiovascular death in subjects aged 70–82.[36] However, the utility of statins in patients over 80 years of age is controversial, as none of the clinical trials have enrolled patients in this age group.[37, 38] In addition, older patients may be at increased risk for statin-related myalgias,[39] and statins may be associated with fatigue, reduced physical activity levels, and cognitive impairment in susceptible older individuals.[4042] Therefore, use of statins in patients of advanced age must be individualized, taking cardiovascular risk profile, life expectancy, prevalent comorbidities, and patient preferences into due consideration.


Other agents Nitrates and morphine are recommended for ongoing chest pain, but neither agent has been shown to reduce mortality or recurrent cardiovascular events. Calcium channel blockers have not been shown to improve outcomes in patients with acute MI, but may be useful in patients with ongoing ischemia, poorly controlled hypertension, or supraventricular tachyarrhythmias (diltiazem or verapamil). Empiric antiarrhythmic drugs (e.g., lidocaine or amiodarone), magnesium therapy, and glucose-insulin-potassium infusions are not recommended in acute MI in the absence of a specific indication. As noted earlier, systemic anticoagulation may be reasonable in select elderly patients with large anterior MI, even in the absence of other compelling indications (atrial fibrillation, mechanical valves, etc.).



Reperfusion in acute ST-segment elevation myocardial infarction (STEMI)


Acute MI associated with ST-segment elevation or new left bundle branch block is usually caused by thrombotic occlusion of the infarct-related coronary artery, and numerous large trials have confirmed that prompt pharmacological or mechanical reperfusion reduces mortality and morbidity.[13] Importantly, although the potential risks of pharmacological reperfusion with fibrinolytic therapy or mechanical reperfusion with percutaneous coronary intervention (PCI) are higher in older patients, the potential benefits are also higher, and the net benefit of reperfusion is at least as great in older as in younger patients. Therefore, older age per se is not a contraindication to thrombolytic therapy, but the benefits of reperfusion must be weighed against the risks of bleeding, which increase exponentially above 75 years of age. Primary PCI is the preferred reperfusion strategy in patients of all ages with STEMI if it can be performed within 90 minutes of presentation because it is associated with higher efficacy and lower risk of intracranial hemorrhage (ICH) relative to fibrinolytic therapy.[13, 43, 44] In situations where PCI cannot be performed within 90 minutes, fibrinolysis is considered a suitable alternative, provided that the risk of bleeding is acceptable (Table 12.4). In this regard, the risk of ICH is approximately twofold higher in patients 75 years of age treated with fibrinolysis compared to younger patients (1%–2% vs. 0.5%–1%).



Table 12.4 Criteria for fibrinolytic therapy in older adults










Indications


  • Symptoms of acute myocardial infarction within 6–12 hours of onset,* and



  • ST-elevation 1 mm in two or more contiguous leads, or left bundle branch block not known to be present previously

Contraindications (absolute)


  • Any prior intracranial hemorrhage or hemorrhagic stroke



  • Ischemic stroke within the past three months (except if within the past three hours)



  • Known malignant intracranial neoplasm or structural vascular lesion



  • Active internal bleeding (excluding menses)



  • Suspected aortic dissection



  • Significant closed head or facial trauma within three months

Contraindications (relative)


  • Blood pressure 180/110 mmHg on presentation, not readily controlled



  • Prior ischemic stroke (>3 months ago)



  • Advanced dementia, other intracranial pathology not described in contraindications



  • Traumatic or prolonged cardiopulmonary resuscitation (>10 minutes)



  • Recent major trauma, surgery, or internal bleeding (within two to four weeks)



  • Noncompressible vascular puncture (e.g., subclavian intravenous line)



  • Active peptic ulcer



  • Pregnancy



  • For streptokinase/anistreplase: prior exposure or allergic reaction to these agents



  • Systemic anticoagulation with warfarin or heparin products at MI presentation (greater coagulopathy = greater hemorrhagic risk)





* Within six hours in patients 75 years of age.



Reperfusion in non-ST-elevation acute coronary syndromes (NSTEACS)


In elderly patients with acute coronary syndromes without ST-segment elevation, thrombolytic therapy is contraindicated and the role of PCI is less clear. Investigators from the thrombolysis in myocardial infarction (TIMI) group have identified seven variables that confer increased risk in individuals presenting with unstable angina or non-ST-elevation MI (Table 12.5).[45] This TIMI Risk Score may aid in triaging patients to an early invasive (i.e., coronary angiography) versus early conservative strategy (i.e., medical therapy, with invasive assessment only for subjects with recurrent ischemia or other clinical indications), and a similar approach is recommended by national guidelines for non-ST-elevation MI.[14] Several of the most important discriminators – including aged 65 and older, elevated cardiac biomarkers (i.e., troponin, creatine kinase-MB), and ST-segment deviation at presentation – have also been associated with higher rates of in-hospital mortality in large observational databases.[46] Since older age is associated with worse outcomes in acute MI, early coronary angiography is recommended in geriatric patients with MI complicated by recurrent ischemia, heart failure, or hemodynamic instability who are suitable candidates for percutaneous or surgical revascularization.[47] However, individualized decision making is required to carefully weigh the risks (e.g., contrast nephropathy, bleeding, potential for stroke or other embolic events) versus benefits related to invasive procedures.



Table 12.5 TIMI Risk Score variables for predicting adverse clinical outcomes in NSTEACS*









  • Aged 65 years or older



  • Three or more risk factors for coronary artery disease



  • Prior coronary stenosis of 50% or more



  • ST-segment deviation on presenting electrocardiogram



  • At least two anginal events in the prior 24 hours



  • Use of aspirin in prior seven days



  • Elevated serum cardiac markers (e.g., troponin)





* The combined endpoint of mortality, myocardial infarction, and urgent revascularization increases in linear fashion, with risk scores 0–1 associated with a 4.7% risk of events at two weeks, versus 8.3% for risk score 2, 13.2% for risk score 3, 19.9% for risk score 4, 26.2% for risk score 5, and 40.9% for risk scores 6–7.


Patients with acute MI at highest risk for death are those presenting with cardiac arrest, heart failure, hypotension, or significant tachycardia, and the in-hospital mortality rate approaches 50% for subjects with cardiogenic shock.[48] Although early coronary revascularization is beneficial in patients up to age 75 presenting with acute MI complicated by cardiogenic shock, the value of this approach in patients over age 75 is less certain.[49, 50] Nevertheless, urgent revascularization is a reasonable option in selected elderly patients in the absence of other life-threatening conditions.



Complications of MI


Heart failure occurs in up to 50% of older patients with acute MI and is the most common cause of in-hospital death. Treatment includes diuretics and vasodilator therapy, especially nitroglycerin and ACE inhibitors. Beta blockers should be administered if blood pressure and heart rate are adequate, and if volume overload is manageable with diuretics. In more advanced heart failure, inotropic agents may be required transiently until the patient stabilizes (e.g., dopamine, dobutamine, milrinone – see the Heart Failure section in this chapter).


Clinically significant right ventricular (RV) ischemia or infarction occurs in 10%–20% of patients with acute inferior STEMI and portends an ominous prognosis in the elderly.[51] Manifestations of RV infarction include hypotension and signs of right-sided heart failure. Treatment involves intravenous fluid administration to maintain LV filling pressure and inotropic therapy if needed.


Life-threatening mechanical complications of MI occur in 1%–2% of all patients and appear to be decreasing in incidence since the advent of acute reperfusion therapy. Mechanical complications include LV free wall rupture with pericardial tamponade, papillary muscle dysfunction or rupture with severe acute mitral regurgitation, rupture of the interventricular septum, and aneurysm or pseudoaneurysm formation. Advanced age is a potent risk factor for each of these catastrophic consequences of acute MI.[52] Care should be individualized, but all forms of rupture require urgent attention and surgical repair, if at all possible. Management of ventricular aneurysm depends on size and degree of hemodynamic instability; in most cases, smaller aneurysms can be managed medically whereas surgical repair should be considered for large aneurysms associated with heart failure or thromboembolic complications. LV pseudoaneurysm refers to a situation in which a free wall rupture has been locally contained by adherent pericardium. Pseudoaneurysms are prone to expand, leading to pericardial tamponade, so surgical repair is recommended.


Sustained ventricular tachyarrhythmias are generally treated with direct-current cardioversion or defibrillation, beta-blocker therapy, and correction of electrolyte abnormalities and ischemia. Selected individuals may require anti-arrhythmic therapy or implantable defibrillators, particularly if new life-threatening ventricular arrhythmias occur more than 48 hours after MI, but these approaches are not indicated for routine management or for prophylactic purposes.[13] Supraventricular arrhythmias such as atrial fibrillation should be treated according to standard recommendations (see the Arrhythmias section in this chapter). Bradyarrhythmias frequently resolve spontaneously once ischemia has been treated, but patients may occasionally require temporary transvenous or transcutaneous pacing. Permanent pacing may be necessary in subjects with persistent high-grade heart block (e.g., Mobitz type II second-degree atrioventricular block or complete heart block in the setting of anterior MI).



Diagnosis and management of chronic coronary disease


After experiencing MI, all patients should be counseled in conjunction with their families or caregivers regarding the medication regimen, diet, and long-term recommendations for CAD management.[53] This is particularly important in elderly patients, for whom sensory or memory deficits combined with polypharmacy may adversely affect medication compliance. Assessment of risk factors should be targeted during the convalescent phase after MI, with nutritional counseling and tobacco cessation efforts addressed prior to discharge.[13, 14] Systolic blood pressure should be controlled in accordance with current guidelines,[54] lipid therapy should be initiated or titrated appropriately using higher potency statins,[55] diabetes management should be addressed,[56] and medical follow-up should be arranged. Cardiac rehabilitation reduces mortality and improves quality of life after MI, with similar benefits in younger and older patients. However, cardiac rehabilitation is significantly underutilized in the geriatric population relative to younger patients.[57]


Chronic CAD, with or without prior MI, increases in prevalence with age – likely as a result of prolonged exposure to multiple cardiac risk factors in conjunction with structural and metabolic changes related to vascular aging. Atherosclerotic changes tend to be more diffuse in older adults, with a higher likelihood of left main and multivessel CAD. Compared to younger patients, geriatric patients tend to present with more advanced disease and fewer or no anginal symptoms due to comorbidities (e.g., diabetes), neuropsychiatric changes, and more sedentary lifestyles. Indications for stress testing are similar to those for younger individuals. However, clinicians should carefully screen geriatric patients prior to stress testing, taking into consideration whether the patient is a suitable candidate for coronary angiography and revascularization, in the event the stress test is abnormal and symptoms persist despite anti-anginal therapy. Often, elderly patients are unable to perform an exercise stress test; in such cases, a pharmacologic test such as a regadenoson nuclear scan or dobutamine echocardiogram is appropriate.[58]


Medical management of chronic stable angina includes aspirin, beta blockers, nitrates, calcium channel blockers, and ranolazine – with beta blockers being the anti-ischemic agents of first choice unless contraindicated.[53] Compared to medical management, coronary revascularization with PCI or coronary artery bypass graft (CABG) surgery reduces symptoms and improves quality of life; CABG also decreases mortality in certain high-risk subgroups (e.g., left main coronary disease, three-vessel disease with LV dysfunction).[59, 60] Coronary angiography, PCI, and CABG in the geriatric population are associated with higher complication rates than in younger patients. [61, 62] Higher mortality in the elderly is due in part to more advanced and diffuse CAD, worse LV function resulting from prior MI, and diminished cardiac reserve related to aging itself. Comorbidities play an important role as well, with vascular and renal disease contributing to procedural difficulty, bleeding complications, and contrast nephropathy. Stroke and other thromboembolic events, as well as heart failure, occur more commonly after either percutaneous or surgical revascularization in older patients. In addition, older patients undergoing CABG experience higher rates of arrhythmias (particularly atrial fibrillation), cognitive dysfunction, and pulmonary complications than younger patients, and these adverse events contribute to increased length of stay and mortality.[63] Despite the attendant risks, outcomes following PCI and CABG in older adults are generally favorable and over 50% of patients undergoing these procedures in the United States are over age 65.[3]




Heart failure and cardiomyopathy



Epidemiology and pathophysiology


More than 5 million Americans have heart failure (HF), and there are more than 1 million hospitalizations with HF as a primary diagnosis each year.[64] HF increases in both incidence and prevalence with increasing age, with up to 75% of HF hospitalizations occurring in patients aged 65 and older and approximately 50% occurring in patients over age 75. In addition, HF is the most costly Medicare diagnosis-related group (DRG), and mortality from HF rises exponentially with age. Age-related changes in cardiovascular structure and function – including increased arterial stiffness, impaired LV diastolic relaxation and compliance, diminished responsiveness to β-adrenergic stimulation, and dysfunction of the sinus node – all contribute to a marked reduction in cardiovascular reserve, predisposing older adults to the development of HF. In addition, increased vascular stiffness leads to a progressive rise in systolic blood pressure, which is a major risk factor for the development of HF in geriatric patients. Indeed, approximately 75% of HF cases have antecedent hypertension, although the increasing prevalence rates of CAD, diabetes, and valvular disease also contribute to the exponential rise in geriatric HF.



Etiology and prevention


Most HF in the geriatric population is related to hypertension and/or CAD. Other common causes include nonischemic dilated cardiomyopathy, valvular disease, and hypertrophic cardiomyopathy. Less common etiologies include myocarditis, constrictive pericarditis, thyroid disease, high-output states such as an arteriovenous fistula or anemia, and infiltrative diseases such as amyloid or hemochromatosis. Individuals with exposure to certain drugs, such as cocaine or chemotherapeutic agents (e.g., anthracyclines and trastuzumab), are also at risk for developing LV dysfunction.


Clinical guidelines emphasize prevention in high-risk populations – especially in subjects with multiple cardiovascular risk factors – and more aggressive titration of therapies in the presence of asymptomatic LV dysfunction, significant valvular disease, or symptomatic HF.[64] Large-scale clinical trials have verified that lowering blood pressure reduces the risk of developing HF,[65] and the greatest benefit is derived from control of systolic hypertension in subjects over age 80.[66] In patients with MI, the syndrome of HF may be delayed for months or years through implementation of the secondary prevention therapies described earlier. In the geriatric population, deconditioning and pulmonary disease may contribute to exercise intolerance, for which rehabilitation and lifestyle modifications are beneficial. Exercise training in particular is recommended in patients with asymptomatic LV dysfunction or chronic HF in the absence of severe symptoms.[64] Pharmacologic regression of LV hypertrophy in hypertensive subjects also reduces the incidence of HF and cardiovascular events.[67] Dietary counseling, including modest sodium restriction and avoidance of excessive fluid intake, may help reduce fluid retention and subsequent HF exacerbations. The importance of medication compliance should be discussed early after diagnosing HF, since medication nonadherence is a leading cause of rehospitalization for HF.



Clinical features and diagnosis


Classic symptoms of HF include shortness of breath (especially with exertion), exercise intolerance, orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, fatigue, and weakness. Elderly patients with HF also commonly experience anorexia, bloating, psychomotor slowing, lethargy, altered sensorium, and gastrointestinal disturbances. Because elderly persons are often sedentary, exertional symptoms may be less prominent than in younger patients. Conversely, “atypical” symptoms such as anorexia and altered cognition become increasingly prevalent.


Assessing symptom severity in patients with HF is useful for identifying therapeutic goals, monitoring disease progression, and determining prognosis. Although there are several metrics available, the New York Heart Association functional classification is most widely used (Table 12.6).[68] Nearly 70% of patients with HF are in class I or II, with mild limitations to routine physical activities. About 25% of patients experience more severe activity limitations (class III), whereas only 5% of patients are class IV, with symptoms during minimal exertion (e.g., going to the bathroom) or at rest. Patients with class IV HF have a one-year mortality rate of 25%–50% – worse than for many forms of metastatic cancer.



Table 12.6 New York Heart Association functional classification





















Class General characteristics
I Cardiac disease does not limit physical activity.


  • Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.

II Cardiac disease results in slight limitation of physical activity.


  • Patients are comfortable at rest.



  • Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

III Cardiac disease results in marked limitation of physical activity.


  • Patients are comfortable at rest.



  • Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.

IV Cardiac disease results in inability to carry on any physical activity without discomfort.


  • Symptoms of cardiac insufficiency or anginal syndrome may be present even at rest.



  • If any physical activity is undertaken, discomfort is increased.


Initial assessment should include a detailed history and physical examination. This is essential in the geriatric population, since patients may not present with typical symptoms or signs, and other medical conditions such as pulmonary disease or deconditioning may confound the clinical picture. Common precipitants of HF exacerbations in the elderly include medication or dietary noncompliance, ischemia, uncontrolled hypertension, new arrhythmias (especially atrial fibrillation), infection, volume overload (e.g., perioperatively or with blood transfusions), anemia, and drug interactions that adversely affect renal or cardiac function. Vital signs and volume status should be evaluated, and complete examination of the neck, chest, cardiovascular system, abdomen, and extremities should be performed. Routine laboratory studies include an assessment of electrolytes and renal function, and a complete blood count.[64] Select patients may require thyroid hormone assessment. An electrocardiogram is indicated, since HF is often precipitated by ischemia or arrhythmia. Chest radiography may be useful for diagnosing volume overload. Echocardiography should be performed at the time of initial diagnosis or when there is unexplained clinical deterioration in order to assess LV systolic and diastolic function, and to identify other structural abnormalities that may be contributing to the HF syndrome.


B-type natriuretic peptide (BNP) and its precursor N-terminal proBNP (NT-proBNP) are released by the myocardium when ventricular filling pressures are elevated, and these biomarkers are useful for both the diagnosis and management of HF.[69, 70] In one large trial, BNP was effective in distinguishing cardiac versus non-cardiac causes of dyspnea in the emergency department.[69] BNP levels increase with age and tend to be higher in women than in men.[71, 72] Other disorders in the geriatric population also contribute to higher BNP levels, including atrial fibrillation, renal dysfunction, and pulmonary hypertension. The predictive accuracy of BNP for diagnosing HF therefore declines with increasing age.[71] Nonetheless, BNP and NT-proBNP frequently add useful diagnostic and prognostic information to the evaluation of subjects with suspected HF. Thus, a normal BNP or NT-proBNP level makes acute HF unlikely, whereas a substantially elevated level of either biomarker greatly increases the likelihood of active HF. Similarly, persistently elevated biomarker levels despite aggressive treatment portend a less favorable prognosis.



Management


Initial goals of therapy for acute HF exacerbations include hemodynamic stabilization and correction of volume overload. Care for elderly patients must be individualized, with comorbid conditions, functional limitations, and personal preferences being taken into consideration in designing a therapeutic plan. In addition, since few clinical trials have enrolled substantial numbers of subjects over age 75, most HF therapies are of unproven benefit in older patients.[73] Multidisciplinary programs that provide individualized patient education and close follow-up have been shown to reduce hospitalizations and improve quality of life in elderly HF subjects.[74, 75] Furthermore, exercise training and cardiac rehabilitation have been associated with improved exercise tolerance in all age groups, leading to recent endorsement of cardiac rehabilitation for stable HF patients with LVEF 35% by the Centers for Medicare and Medicaid Services.[76]


Diuretics Loop diuretics are an essential component of the acute management of HF with volume overload. Administered intravenously, these agents promote rapid natriuresis and increased urine output. Older patients are more sensitive to diuretic-induced electrolyte disturbances and volume shifts than younger subjects, so close monitoring is imperative in conjunction with regular assessments of renal function and electrolytes. Although loop diuretics have not been shown to improve survival, and there are conflicting data concerning the short and long-term benefits of these agents,[7779] relief of congestion is a primary goal of initial HF therapy.[80] In patients who do not respond adequately to loop diuretics, the addition of metolazone (usually administered 30–60 minutes before the loop diuretic) may facilitate diuresis, but renal and electrolyte disturbances are common. Dietary sodium restriction helps prevent fluid retention, and patients should be counseled to avoid salty foods and limit sodium intake to no more than 2 grams per day. Conversely, over-zealous sodium restriction has not been shown to improve outcomes and may be harmful.[81] Patients should also be instructed to monitor daily weights at home. A baseline “dry weight” should be defined, and subjects should be advised to adjust their diuretic dosage or contact their healthcare provider if their weight varies by more than two to three pounds from baseline over several days.


ACE inhibitors In patients with HF and reduced ejection fraction (HFrEF), angiotensin converting enzyme inhibitors (ACEI) reduce HF hospitalizations, improve quality of life, and decrease mortality by 25%–30% – with similar effects in older and younger subjects.[82, 83] Older patients experience higher rates of hypotension, hyperkalemia, and renal dysfunction during ACEI titration than younger individuals; close monitoring of these parameters is warranted. Up to 20% of patients may experience cough and a small percentage may experience angioedema from ACEI, but these side effects do not appear to increase in frequency with advancing age. In the absence of adverse effects, ACEI dosages should be titrated to those studied in clinical trials (e.g., captopril 50 mg tid, enalapril 10 mg bid, lisinopril 20 mg–40 mg q day, ramipril 10 mg q day). In addition, ACEI therapy in patients with asymptomatic LV dysfunction reduces progression to clinical HF,[84] so ACEI are indicated in patients with LV systolic dysfunction (LV ejection fraction <40%–45%) regardless of New York Heart Association functional class.[64]


Angiotensin receptor blockers While ACEI are recommended as first line therapy for patients with HFrEF, angiotensin receptor blockers (ARBs) are suitable alternatives in individuals intolerant to ACEI due to cough or angioedema.[85,86] In a series of three trials involving patients with HF, the ARB candesartan reduced the composite endpoint of death or HF hospitalization by 13.8% among 1,736 subjects 75 years of age (p = 0.007), and the benefit was at least as great in this age group as in younger patients.[87] As with ACEI, older patients receiving ARBs are at increased risk for hypotension, renal dysfunction, and hyperkalemia. In addition, combination therapy with an ACEI and ARB is not recommended due to lack of proven benefit and increased risk for adverse effects.[88]


Hydralazine-nitrates The combination of hydralazine and nitrates improves clinical outcomes in HFrEF.[89] Although mortality reduction is less than with ACEI therapy, this combination is useful in subjects with renal dysfunction or hyperkalemia that precludes the use of ACEIs or ARBs.[90] Moreover, in the African-American Heart Failure Trial (A-HeFT), the combination of hydralazine and isosorbide dinitrate taken three times daily improved clinical outcomes in class III–IV HF subjects already treated with standard therapies including ACEIs and beta blockers.[91] All subjects in A-HeFT were African American, and the mean age was 57, so the role of these agents in older patients and in other racial/ethnic groups remains to be determined. Another important concern is the need for multiple daily doses of both agents, which may be problematic in elderly patients with polypharmacy and medication adherence difficulties.


Beta blockers Beta blockers improve LV function, decrease hospitalizations, and reduce mortality in a broad range of patients with HFrEF, and three beta blockers are indicated for management of HFrEF (metoprolol succinate, carvedilol, and bisoprolol).[9294] However, geriatric patients are often sensitive to beta blockade, so initiation at a low dose with slow upward titration is imperative in order to avoid bradycardia, heart block, hypotension, or worsening HF. In particular, patients with class III–IV HF require meticulous and slow titration due to the potential for transient worsening of symptoms. Active bronchospasm is a contraindication to beta-blocker therapy, but chronic pulmonary disease does not preclude use of these drugs. Other contraindications include marked bradycardia, advanced heart block, hypotension, and severe decompensated HF.


Mineralocorticoid antagonists Spironolactone and eplerenone are mineralocorticoid antagonists (MRAs) with weak diuretic potency but with antifibrotic properties and other beneficial cardiovascular effects. When added to other therapies in class II–IV HFrEF, LVEF 35%, and class II–IV symptoms, these agents reduce mortality and hospitalizations by approximately 25%–30%.[95, 96] The benefits are similar in older and younger subjects, but older patients are more susceptible to worsening renal function and hyperkalemia.[97] Meticulous electrolyte and renal surveillance is therefore required in geriatric HF patients treated with MRA. Up to 10% of patients may develop gynecomastia and breast tenderness with spironolactone, but these side effects are rare with eplerenone.


Digoxin Digoxin reduces HF symptoms and hospitalizations but has no effect on mortality.[98] The benefits and adverse effects of digoxin are similar in older and younger patients – including those over age 80.[99] In addition, retrospective analysis of the Digitalis Investigation Group (DIG) trial suggests that digoxin may have a favorable effect on mortality when the serum digoxin level is maintained at <1.0 ng/mL.[100] In geriatric patients with persistent HF symptoms despite other therapeutic measures, digoxin should be initiated at a low dose (0.125 mg daily in the absence of renal dysfunction) with close monitoring for side effects such as bradycardia, heart block, arrhythmias, gastrointestinal symptoms, and mental status changes or visual disturbances. Digoxin toxicity occurs more frequently in the setting of hypokalemia, hypomagnesemia, hypercalcemia, and concurrent use of amiodarone, verapamil, and several other medications.


Anticoagulant and anti-inflammatory drugs Although the thromboembolic risk associated with HFrEF approaches that seen in atrial fibrillation, two large clinical trials failed to demonstrate a net clinical benefit from therapeutic anticoagulation with warfarin in HF patients.[101, 102] Warfarin or other anticoagulant treatment should therefore be reserved for patients with mechanical heart valves, atrial fibrillation, or other compelling indications.[64] Aspirin should be prescribed in patients with CAD, peripheral arterial disease, diabetes, or other indications for antiplatelet therapy. The value of aspirin in HF patients without clear indications for its use is uncertain. Nonsteroidal anti-inflammatory medications (other than aspirin) – commonly used to treat arthritis and chronic pain in older individuals – should be avoided in HF patients whenever possible because these agents promote sodium and water retention, antagonize ACEIs and other HF medications, and may worsen renal function.


Inotropic agents and intravenous vasodilators Intravenous inotropic agents, such as dobutamine and milrinone, have not been shown to improve clinical outcomes and have been associated with increased mortality rates in patients with advanced HF.[103, 104] Nevertheless, many clinicians utilize intravenous inotropes to alleviate symptoms in patients with severe intractable HF unresponsive to standard therapies. Intravenous nitroglycerin and nitroprusside have favorable hemodynamic effects in patients with severe HF, especially in those with poorly controlled hypertension or significant aortic or mitral regurgitation. Both agents may cause hypotension, and caution is advised in using nitroprusside in older patients, especially those with impaired renal function. Nesiritide, a recombinant form of BNP administered intravenously, has been shown to reduce LV filling pressures more effectively than intravenous nitrates or standard therapy (including diuretics), but nesiritide has not been shown to reduce morbidity or mortality.[105, 106] Routine use of nesiritide in patients with HF is not currently recommended.[64]



Heart transplantation and mechanical circulatory support


Although being 75 or more years of age is considered a contraindication to orthotopic heart transplantation (OHT) at most centers in the United States, a growing proportion of transplant recipients are 65–74 years of age, and outcomes are similar in this age group compared to younger patients.[107] However, the number of candidates for OHT greatly exceeds the number of donor hearts available, so only a small proportion of highly selected patients with advanced HF undergo the procedure. More recently, technological advances in mechanical circulatory support systems, particularly the development of continuous-flow left ventricular assist devices (LVADs), have led to more widespread use of LVADs as “destination therapy,” rather than as a bridge to transplantation. To date, experience with LVADs in patients 70–74 years of age has been generally favorable with improved quality of life and functional status and an acceptable complication rate.[108] Data are limited in patients 80 years of age, but use of LVADs in this population is likely to increase as the technology continues to improve and complication rates decline. The most common complications associated with continuous-flow LVADs include bleeding (especially gastrointestinal bleeding), infections, and stroke. Outcomes following LVAD implantation are also dependent on comorbidity burden, baseline function status, and frailty, so careful patient selection is critical to the long-term success of mechanical circulatory support.



Heart failure with preserved ejection fraction


Approximately half of older adults with HF have a preserved LV ejection fraction (HFpEF).[109, 110] The impact of HFpEF on exercise tolerance, symptoms, and hospitalization rates is similar to that of HFrEF, although mortality rates tend to be somewhat lower.[111113] In contrast to HFrEF, however, for which multiple pharmacological and device-based interventions have been associated with improved clinical outcomes, including mortality, to date no therapies have been shown to reduce mortality in patients with HFpEF.[114123] As shown in Table 12.7, some studies have reported favorable effects on hospitalizations and/or exercise tolerance, but in general the magnitude of these effects has been modest. Thus, optimal management of HFpEF remains undefined.



Table 12.7 Pharmacotherapy trials for heart failure with preserved ejection fraction
















































































Trial* Patients Treatment LVEF Age Outcomes compared to placebo**
PEP-CHF 850 Perindopril 65 (56–66) 75 (72–79) Death/hospitalization by 1 year – HR 0.69 (0.47–1.01, p = 0.055); HF hospitalization by 1 year – HR 0.63 (0.41–0.97, p = 0.033)
CHARM-Preserved 3,023 Candesartan 54 ± 9 67 ± 11 CV death/HF admission – HR 0.89 (0.77–1.03, p = 0.118); HF admission – HR 0.85 (0.72–1.01, p = 0.072)
I-PRESERVE 4,128 Irbesartan 60 ± 9 72 ± 7 Death/hospitalization – HR 0.95 (0.86–1.05, p = 0.35)
SENIORS (EF >35% subgroup) 643 Nebivolol 49 ± 10 76 ± 5 All cause death/CV hospitalization – HR 0.81 (0.63–1.04)
TOPCAT 3,445 Spironolactone 56 (51–62) 69 (61–76) CV death/HF hospitalization/aborted SCD – HR 0.89 (0.77–1.04, p = 0.14); HF hospitalization – HR 0.83 (0.69–0.99, p = 0.04)
Aldo-DHF 422 Spironolactone 67 ± 8 67 ± 8 Reduced E/e’ avg 1.5 (p < 0.001)
RELAX 216 Sildenafil 60 (56–65) 69 (62–77) No difference Δ VO2 peak at 24 weeks
ESS-DHF 192 Sitaxsentan 61 ± 12 65 ± 10 Median 43 second relative increase in Naughton treadmill time (p = 0.03)
DIG Ancillary 988 Digoxin 55 ± 8 67 ± 10 HF hospitalization – HR 0.79 (0.59 – 1.04, p = 0.09); hospitalization for unstable angina – HR 1.37 (0.99–1.91, p = 0.06)


Abbreviations: LVEF = left ventricular ejection fraction; E/e’ avg = echocardiographic mitral inflow velocity/tissue Doppler velocity ratio; CV = cardiovascular; VO2 = oxygen consumption; SCD = sudden cardiac death; HR = hazard ratio (with 95% confidence interval)


Age (in years) and LVEF (%) presented as mean ± Standard Deviation (SD) or Interquartile Range (IQR).




* Trial acronyms: PEP-CHF = Perindopril in Elderly People with Chronic Heart Failure; CHARM-Preserved = Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity – Preserved LVEF; I-PRESERVE = Irbesartan in heart failure with Preserved ejection fraction study; SENIORS = Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in seniors with heart failure; TOPCAT = Treatment Of Preserved Cardiac function heart failure with an Aldosterone antagonist; Aldo-DHF = Aldosterone receptor blockade in Diastolic Heart Failure; RELAX = Phosphodiesterase-5 inhibition to improve clinical status and exercise capacity in heart failure with preserved ejection fraction; ESS-DHF = Effectiveness of Sitaxsentan Sodium in patients with Diastolic Heart Failure; DIG Ancillary = Digitalis Investigation Group Ancillary trial



** All-cause mortality was not significantly reduced in any trial.


Current recommendations for managing HFpEF focus on controlling heart rate, blood pressure, and volume status.[64] Hypertension should be treated in accordance with existing guidelines. Precipitating factors, such as ischemia or arrhythmia, should be managed appropriately, and judicious diuresis should be undertaken with close monitoring of blood pressure and renal function. Important differential diagnostic considerations in patients with HFpEF include valvular heart disease, pericardial constriction, restrictive cardiomyopathy (e.g., amyloidosis, hemochromatosis, sarcoidosis), and noncardiac etiologies such as pulmonary disease with right heart failure. Hypertrophic cardiomyopathy (HCM) may also mimic HFpEF and may be associated with exertional chest pain and syncope. Since the therapeutic armamentarium for HFpEF is limited, identification and treatment of potentially reversible causes of the patient’s symptoms is essential.



Device therapy in advanced heart failure


Implantable devices Although pharmacological and behavioral therapies are the cornerstones of HF management, implantable devices are playing an increasingly important role in the treatment of HF patients. Advanced HF frequently is associated with dyssynchronous LV contraction related to abnormalities of electrical conduction, and cardiac resynchronization therapy (CRT) improves symptoms and clinical outcomes in patients with NYHA class II–IV HF, LVEF 35%, and a QRS duration 150 msec on the electrocardiogram, especially with left bundle branch block morphology.[124126] Interestingly, the benefits of CRT appear to be greater in women than in men, and recent data suggest that some women with QRS duration 130 msec but <150 msec may also benefit.[127, 128] Although none of the CRT trials enrolled patients over 80 years of age, observational studies indicate that selected octogenarians may derive significant quality of life benefit from CRT.[129] Thus, CRT should be considered in elderly patients with persistent advanced HF symptoms who otherwise meet criteria for the device.


Implantable cardioverter-defibrillators (ICDs) reduce the risk for sudden cardiac death (SCD) in selected patients at increased risk for such events.[130, 131] Current criteria for ICD implantation include an LVEF 35%, NYHA class II–III symptoms, and a life-expectancy of at least 1 year with good functional status.[126] However, few patients over 80 years of age were enrolled in the major ICD trials, and there is evidence that the life-saving benefits of ICDs decline with age, most likely due to competing morbidities.[132] Thus, although age is not a contraindication to an ICD, device implantation should be undertaken only after careful consideration of the potential benefits and risks through a process of shared decision making. In addition, a discussion of circumstances under which the patient would want to disable the ICD to avoid painful shocks (e.g., in the event of terminal illness) should occur prior to device implantation in all patients, regardless of age.[133]



Rehospitalizations and prognosis


Approximately 20%–25% of patients discharged from the hospital with a primary diagnosis of HF are readmitted within 30 days, and up to 50% are readmitted within six months. These readmissions contribute substantially to the total cost of caring for HF patients, and hospitals with excess risk-adjusted 30-day readmission rates are subject to financial penalties under the Affordable Care Act’s Hospital Readmission Reduction Program. In addition, 30-day readmission rates are widely used as quality metrics to assess performance of both hospitals and physicians. Over the past two decades, numerous studies have tested various interventions designed to reduce readmissions in selected patients with HF. These interventions generally include individualized patient and family education aimed at enhancing HF self-care in conjunction with close follow-up in the days and weeks immediately following discharge. Although randomized trials and meta-analyses have shown that such interventions reduce all-cause readmissions by 20%–25%, the effectiveness of “disease management” programs in improving outcomes on a population-wide basis has not been established.[134] Furthermore, since approximately two-thirds of early readmissions are for reasons other than HF, additional research is needed to develop and test novel interventions designed to manage HF in the context of multiple chronic conditions.


The overall prognosis for elderly patients with HF remains poor, with one-year mortality rates of up to 25% and five-year mortality rates of 75%–80%. Factors associated with worse prognosis include older age, more severe symptoms (New York Heart Association functional class III–IV), ischemic etiology, renal insufficiency, hyponatremia, peripheral arterial disease, and dementia.[135] Patients with HFpEF have a somewhat more favorable short-term prognosis than subjects with HFrEF, but long-term prognosis is similar. In light of the high mortality associated with HF, which is equivalent or worse than many forms of cancer, it is appropriate to begin to address goals of care and end-of-life issues early in the course of illness.[136] HF patients should be advised to develop a living will or advance directive and to designate durable power of attorney for health care in the event that decision-making capacity is lost, either temporarily or permanently. In patients with advanced HF and NYHA class IV symptoms despite optimal therapy, life expectancy is less than six months. In such cases, transition to palliative care or hospice should be considered.

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Feb 26, 2017 | Posted by in GERIATRICS | Comments Off on Diagnosis and management of heart disease in the elderly

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