Heart failure is the commonest hospital discharge diagnosis in patients over the age of 65 years. Congestive Heart Failure represents the only major cardiovascular syndrome to increase in incidence over the next twenty-five years. The elderly, and elderly women in particular, have often been excluded from clinical trials in cardiovascular medicine.
Heart failure is the commonest hospital discharge diagnosis in patients over the age of 65 years. Congestive Heart Failure represents the only major cardiovascular syndrome to increase in incidence over the next twenty-five years. The elderly, and elderly women in particular, have often been excluded from clinical trials in cardiovascular medicine.
Heart failure is the commonest hospital discharge diagnosis in patients over the age of 65 years. Congestive Heart Failure represents the only major cardiovascular syndrome to increase in incidence over the next twenty-five years. The elderly, and elderly women in particular, have often been excluded from clinical trials in cardiovascular medicine.
Heart failure is the commonest hospital discharge diagnosis in patients over the age of 65 years. Congestive Heart Failure represents the only major cardiovascular syndrome to increase in incidence over the next twenty-five years. The elderly, and elderly women in particular, have often been excluded from clinical trials in cardiovascular medicine.
Dr. Malcolm Arnold Division of Cardiology University of Western Ontario London Health Sciences Centre Victoria Campus 375 South St, Room S226A London, ON N6A 4G5
Email: Malcolm.Arnold@lhsc.on.ca
It is estimated that over 350,000 Canadians suffer from congestive heart failure. As a clinical entity, it represents the only major cardiovascular syndrome expected to increase in incidence over the next twenty-five years. 1 Heart failure is currently the commonest hospital discharge diagnosis in patients over the age of 65 years. While recent Canadian guidelines have been published regarding the diagnosis and management of heart failure, 2 there are reasons to believe that particular attention is required with regard to their implementation in the elderly. Adherence rates to medical therapies recommended in previously published guidelines have been demonstrated to be lower in older patients. 3 The elderly, and elderly women in particular have often been excluded from clinical trials in cardiovascular medicine and, therefore, strict application of evidence based guidelines may not account for different characteristics and co-morbidities in this population. 4 Thus, important opportunities exist for research and education regarding the special needs of older patients with heart failure. In aging populations, a variety of chronic diseases are more prevalent than in younger subjects. Typically, latent periods are long and symptoms, although often non-specific, should be carefully distinguished from normal aging. 5 Identification of high-risk individuals may be beneficial, if interventions modify disease expression and the progression of disability. 6 Quality of living, preservation of functional independence and cognitive function, as well as end of life issues may be more important for many than prolonged survival.
Elderly patients with heart disease and failure are more likely to be frail 7 and cognitively impaired 8,9 , are more likely to require home care, hospitalization, or institutionalization, and have an increased mortality. 10,11,12,13,14,15
Cognitive impairment in heart failure is multifactorial as both conditions share common risk factors, including atherosclerosis, hypertension and diabetes mellitus. Hemodynamic abnormalities due to heart failure (including poor systolic dysfunction, low cardiac output and hypotension) are associated with cognitive impairment in hospitalized patients. 16,17 Dehydration and electrolyte disturbances, which often arise from excessive diuresis, can predispose to delirium. 18
The impact of frailty and cognitive impairment in elderly patients with CHF is significant. Such patients with CHF are more likely to present with atypical symptoms, such as delirium, functional decline, falls, immobility, nocturia and nocturnal incontinence. 19 Cognitive impairment in patients with CHF has been associated with non-adherence to therapy, medication mismanagement, non-participation in outpatient treatment programs, accelerated functional decline and failure to recognize symptoms and seek medical attention in a timely manner. 20,21,22,23,24
Demographics: Based on several recent population studies, the typical heart failure patient is elderly (often over the age of 80) and women are affected almost as frequently as men, unlike heart disease in younger individuals. The initial diagnosis is often made in hospital. 11,25,26 Symptoms may be advanced at the time of initial diagnosis (NYHA III-IV). Co-morbid conditions such as renal dysfunction, COPD, arthritis, hypertension, diabetes and cognitive impairment or depression are common. Ischemic heart disease and hypertension are the most common etiologies of heart failure in this population.
Many elderly patients with heart failure (over 40-50% in some series) have preserved left ventricular systolic function (diastolic heart failure). 27 Abnormalities in left ventricular filling and/or relaxation result in elevated diastolic filling pressures, which are transmitted to the pulmonary and systemic venous circulations. Longstanding hypertension, particularly in elderly women may give rise to a form of (hypertensive) hypertrophic cardiomyopathy. Ischemia may precipitate acute pulmonary edema in spite of normal left ventricular systolic function. As diastolic function becomes progressively impaired, the left ventricle becomes increasingly dependent on atrial systole for adequate filling. Loss of atrial systole (atrial fibrillation) may precipitate acute pulmonary edema. While mortality rates for heart failure associated with preserved left ventricular systolic function are approximately half of that for patients with left ventricular systolic dysfunction, all cause- and CHF admissions to hospital are similar. 28 Large randomized trials in the treatment of heart failure associated with preserved left ventricular systolic function are lacking (although in progress) and current guidelines for the most part recommend aggressively treating the conditions thought to be responsible (hypertension, ischemia, arrhythmia).
Prognosis Survival rates for elderly patients with heart failure typically average less than 35% at five years. Among community-dwelling elderly patients hospitalized for heart failure, one-year survival rates may be as low as 50%. In one retrospective study of very elderly (mean age 89yrs) long-term care residents hospitalized with CHF, one-year mortality was 87%. 29 Prognosis worsens with increasing New York Heart Association functional class. A variety of medical (blood pressure, co-morbidities, functional status) 30 , social (marital status, social isolation) 31 , and psychosocial (in particular depression and self-rated health) 32
33 factors have significant effects on survival. To what extent particular attention to these factors in the patient with heart failure may modify outcomes is an area worthy of further research.
Prevention and Screening Screening for heart failure and treatment of patients at increased risk of developing heart failure are useful if interventions can modify the natural history of the condition and are safe and evidence-based.
Control of systolic hypertension in the elderly is important in the prevention of heart failure, especially in patients with a past history of myocardial infarction. The SHEP Trial 34 demonstrated that the risk of heart failure could be significantly attenuated in such patients by blood pressure lowering with a thiazide diuretic as first line therapy and similar findings were obtained recently in ALLHAT. 35 The SOLVD Prevention Trial demonstrated that treatment of asymptomatic left ventricular systolic dysfunction (LVEF<35%) with an angiotensin-converting enzyme inhibitor (enalapril 10 mg BID) could delay the expression of symptoms of heart failure by an average of eighteen months, but patients over the age of eighty were not randomized into this study. 36
Frail, elderly in-patients appear to be at elevated risk for iatrogenic heart failure (secondary to administration of fluids or blood products, or as a result of medication effect or procedural complications). Hospital mortality is particularly high in this group, and lengths of stay are prolonged. 37 Intravenous fluids need to be administered with caution and close monitoring. Commonly used drugs (all NSAIDS, thiazolidinediones and corticosteroids) may precipitate heart failure in patients not recognized to be at increased risk. Excess salt or fluid in the diet may cause fluid retention in susceptible individuals. Further research is needed to define at-risk populations and management strategies.
Diagnosis and Investigations The goals of heart failure management include alleviation of symptoms, prevention of progression of disease and hospitalization, and where possible, maintenance of functional capacity and improvement in life expectancy. Symptoms of heart failure (fatigue, breathlessness) may be confused with normal aging. Delirium, a marked decline in functional status, recent onset of peripheral edema, or nocturnal symptoms (cough, dyspnea, nocturia, incontinence) warrant further investigations for heart failure. The evaluation of older patients suspected of having heart failure should attempt not only to confirm a clinical suspicion, but also document the presence of co-morbid conditions contributing to disability. All elderly patients with a diagnosis of heart failure should have a well-documented social history including their home environment, their caregivers, and their response to an emergency. Elderly patients with CHF should be screened for cognitive impairment and suitable tools include the Mini-Mental State Examination 38,39 , and Clock test. 40
Hospitalizations are common and may be preventable. 41 Frail or cognitively impaired elderly and complex heart failure patients should be referred to specialized services (e.g. comprehensive geriatric assessment, CHF clinics) where available.
The basic investigations for heart failure do not significantly differ in the older patient and include complete blood count, routine biochemistry, including renal and liver function tests, and thyroid-stimulating hormone assay (given a high prevalence of thyroid dysfunction in the elderly), chest x-ray and electrocardiogram. As in younger individuals there should be an objective assessment of left ventricular function. 42 Patients presenting with acute pulmonary edema should undergo investigations and evaluation to determine contributing causes
(infection, ischemia, arrhythmia, medication changes or non- compliance). Other investigations would depend on the level of suspicion for other disorders based on the presenting history and physical. The appropriateness of referral for invasive investigations for coronary or valvular heart disease must be individualized: it should not be based on a consideration of chronological age alone, but should be based on an estimation of active life expectancy, anticipation of benefit and the risks associated with intervening All elderly patients with heart failure should be offered pneumococcal and influenza vaccines.
Exercise and Lifestyle Modification The theoretical benefits of exercise in heart failure include reduced neurohormonal activation, improved endothelial function and skeletal muscle physiology and improved perceived quality of life. Most studies demonstrating the benefits of exercise in heart failure have enrolled patients under the age of 60, and results cannot necessarily be extrapolated to frailer, older adults. 43 Because lower extremity strength is closely associated with independent living, it is reasonable, where possible to recommend some form of low intensity training even in very elderly patients. Education of patients and caregivers is advisable, particularly with regard to dietary changes (salt and fluid restriction) and the value of exercise. Financial constraints and living conditions may limit the range of foods available. Foods typically rich in sodium (canned soups, cured meats and frozen dinners) often represent a convenient source of calories, but may exacerbate heart failure. Home care nurses, dieticians, physical and occupational therapists, and social workers may offer valuable resources for maintaining older patients in the community. Medication surveillance, dietary advice, exercise prescription, energy conservation techniques and recommendations for assistive devices or referral to specialized services (day hospitals, day-away programs, CHF clinics) may provide crucial support to maintain patients in the community.
Drug Therapy in CHF There are limited data regarding optimal drug therapy for heart failure in the very old (age>80). There is no reason to believe, on the other hand, that pharmacological therapy of heart failure in the elderly is inherently dangerous, although polypharmacy may pose certain hazards in an aging population. Small studies and subgroup analyses in large clinical trials have demonstrated the safety and efficacy of standard therapies in elderly patients with CHF and these have been reviewed in recent Canadian Guidelines. 2
Diuretics should be prescribed in all patients with symptoms or signs of pulmonary or systemic congestion. Once daily dosing is preferable and monitoring of renal function and electrolyte balance should follow changes in therapy. Patients experiencing symptoms of hypo perfusion or worsening renal insufficiency during up- titration of neurohormonal blockade therapy should have the dose of diuretic divided or reduced. During long- term therapy, the dose of diuretic may have to be adjusted several times to allow uptitration of other drugs and to achieve the lowest dose compatible with stable weight and symptoms.
Digoxin was a mainstay of therapy in congestive heart failure although there have been reports of over- utilization in the elderly. These have been from trials, which have shown that as many as 75% of patients appeared to experience no adverse effects after digoxin was discontinued. These trials often did not include an assessment of left ventricular function or strict definitions of heart failure. Digitalis toxicity may present atypically in older subjects (falls, anorexia, depression, confusion) and may occur at normal serum levels. 44 The Digitalis Investigation Group (DIG) study evaluated the benefit of digoxin in patients with stable heart failure mainly due to left ventricular systolic dysfunction (LVEF < 45%) but a smaller ancillary study also evaluated patients with LVEF >45%. Twenty seven percent of patients in the main trial were >70yrs of age. While advancing age was an independent risk factor for complications of digoxin therapy (toxicity, hospitalization for toxicity), the benefits of therapy to reduce hospitalizations were maintained across all age groups. 45 Total mortality was not reduced. In the DIG study, digoxin dose was adjusted using an algorithm for age, sex, weight, and renal function 46 . Despite this, post hoc analysis of the trial results found that women with CHF may be a greater risk of death if they taking digoxin 47 . Careful use of digoxin, especially in those with significant renal dysfunction, may be helpful for symptomatic control and to reduce hospitalizations in those with severe symptoms and very poor heart function.
Angiotensin converting enzyme (ACE) inhibitors should be considered in all elderly patients with chronic heart failure although there are limited data on their effectiveness in older subjects. The CONSENSUS Trial 48
(enalapril) excluded patients over the age of 75, and the SOLVD 49 (enalapril) and SAVE 50 (captopril) trials excluded patients over the age of 80. The AIRE (ramipril) Trial 51 did not exclude patients on the basis of age alone, and while there was a trend toward better outcomes in the population over the age of 65, numbers were not great enough to reach statistical significance. A recent small-randomized trial of 66 patients (mean age 81 yrs) with symptomatic systolic heart failure showed that perindopril was associated with a statistically significant 37-meter increase in 6-minute walking distance over 10 weeks. 52 For a frail older person, the magnitude of this effect could mean the difference between being independent or housebound but the results need confirmed in a larger trial. Preliminary evidence from a non-randomized cohort study suggests that ACE inhibitors, compared to digoxin, may reduce the rate of functional decline in elderly patients (mean 85yrs) with heart failure after transfer to a nursing home from an acute care hospital. 53
Because of the importance of ACE-inhibitors in heart failure management, some caveats are helpful to maximize success. When introducing and uptitrating the dose of an ACE-inhibitor in the elderly, it is important to start with low doses and increase slowly towards target clinical trial doses (enalapril 10 mg bid, lisinopril 20mg od, ramipril 10 mg daily, captopril 50 mg tid) or a lesser maximally tolerated dose. The dose of diuretic may be reduced if there is no fluid retention to maintain stable blood pressure. In some elderly patients it may be helpful to separate the timing of the ACE-inhibitor and diuretic doses to avoid peak hemodynamic effects. Blood pressure should be measured standing as well as sitting or supine. Renal function and serum potassium should be followed and rechecked after changes in ACE-inhibitor or diuretic dose or with a significant change in clinical condition. A twenty percent increase in serum creatinine is not unexpected based on how the medications work and, if stable, is not sufficient reason in itself to discontinue the drug.
The Elite II Trial randomized only patients over the age of sixty and compared the ACE-inhibitor captopril with the angiotensin receptor blocker losartan. The trial failed to demonstrate the superiority of losartan in the elderly, but the drug tended to be better tolerated (fewer withdrawals due to cough). 54 The equivalence of angiotensin receptor blockers to ACE inhibitors in reducing mortality from CHF remains to be confirmed. 55 The addition of valsartan to an ACE-inhibitor may reduce heart failure hospitalizations particularly in those not on a beta-blocker.
Spironolactone in low doses (mean 26 mg/day) was investigated in the RALES Trial 56 which enrolled a population of patients (mean age 65yrs) with advanced (NYHA III-IV, LVEF <35%) heart failure, being treated with an ACE-inhibitor and loop diuretic, but excluded patients with renal impairment (creatinine >220micromoles/l) or other significant co-morbidities. Spironolactone significantly reduced mortality by 30% and hospitalizations for worsening heart failure by 35%, and significantly improved NHYA functional class. Thus, low doses of spironolactone are recommended in patients with severe heart failure despite optimized medical management. Gynaecomastia occurred in 10% of men. Note should also be taken that serum potassium and renal function were followed closely in the study at 1, 2, 3, 6, 9 and 12 months and 6 monthly thereafter. With this close surveillance, there was no excess of hyperkalemia or renal dysfunction. Unless hypokalemia (<3.5 mmol/l) is present, oral potassium supplements are not recommended.
Beta-blockers may also be useful in older patients, as the activation of the sympathetic nervous system appears to be proportionately greater than that of the renin-angiotensin system. On a background of ACE-inhibitors and other standard therapy at the time, beta-blockers improved survival by 30-35% and also improved left ventricular function. However, older patients have not been well represented in the large beta-blocker trials and withdrawal rates tended to be higher. Standard contraindications to beta-blocker use apply, including second or third degree heart block and significant reactive airways disease. Concerns about beta-blocker effects on cognition appear to be based more on anecdotal reports rather than rigorous scientific evidence and concerns about potential side effects should not deter physicians from treating elderly patients with symptomatic heart failure. The beta-blocker should be started in very low doses, increased slowly over several weeks to months, but target doses would be metoprolol 75mg bid, carvedilol 25 mg bid, and bisoprolol 10 mg od (these drugs
were studied in the recent major trials). Follow up should include monitoring of heart rate, blood pressure and symptoms, and adjustment in concomitant medications as required. If a side-effect attributable to the beta- blocker occurs, the drug may be reduced to the previously well tolerated dose for an extra few weeks and then uptitration repeated with a lesser incremental dose. Patients on a stable dose of beta-blocker, presenting with decompensated heart failure, may have their dose of beta-blocker reduced by 50% temporarily but generally the drug does not have to be discontinued permanently.
Many of the drugs used in the treatment of heart failure exhibit altered pharmacokinetics (e.g. digoxin) and pharmacodynamics (e.g. beta-blockers) in the elderly. Renal function typically declines with aging and a serum creatinine level, for example, of 80 mmol/l in a slender octogenarian does not necessarily imply normal renal function. Renal function can be evaluated using timed urine collections or estimated using methods such as the Cockcroft-Gault equation, and drug dosages adjusted accordingly. 57
Existing guidelines would appear to be reliable in patients up to the age of 80 years without significant co- morbidities, but caution should be used in extrapolating these trials to older or sicker elderly patients. The elderly are at greater risk for complications of side effects (falls, fractures, renal failure) and care must be taken in initiating drug therapies known to influence blood pressure, electrolyte balance and renal function, even in the presence of normal indices of renal function. Elderly patients are particularly sensitive to hypotension associated with loop diuretics 58 . There is also evidence to suggest that long-acting ACE inhibitors are associated with less first-dose hypotension than shorter acting preparations 59 . Renal dysfunction that occurs when ACE inhibitors are introduced is generally attributable to over-diuresis or use of NSAIDS 60 . In view of possible dangers of drug effects, and in the absence of clinical trials enrolling sufficient numbers of elderly subjects, agents should be slowly titrated to a maximally tolerated dose even if that be less than the clinical trail target dose. Treatment programs should strive to simplify drug regimes by, for example, selecting drugs administered on a once daily basis, and emphasizing the avoidance of diuretic administration late in the day to reduce nocturia.
The concomitant use of drugs of limited value (e.g. NSAIDS 61 for osteoarthritis), which may potentially worsen symptoms and complicate therapy, should be discouraged when safer alternatives (e.g. acetaminophen) exist.
CHF Clinics There is clearly a need for expanding the role of CHF clinics in the management of frail elderly patients with CHF. High-risk patients in hospital can be identified with simple criteria and a comprehensive multi- dimensional assessment has been shown to significantly reduce subsequent hospitalizations and lengths of stay. 62 Such clinics can also serve as a resource to families and local health care providers. Institutions and health care authorities should encourage the development of such clinics and the role of the clinic nurse as case manager. Where resources are available, geriatricians, rehabilitation specialists, dietitians, social workers, pharmacists, clergy and others can all play a valuable role. 63 Home-based care with visiting nurses or interactive telecommunications may be particularly well suited for rural areas.
Recommendations for future research and education: Relatively little is known about the majority of elderly patients suffering from heart failure. Research is needed to better define the characteristics of the population and their special needs. Enhanced geriatric teaching in internal medicine and cardiology training programs has been advocated as a means of improving care of the elderly and stimulating an interest in research issues. There are significant co-morbidities such as depression, frailty and cognitive impairment which have been shown to impact significantly on adverse outcomes such as functional decline, home care service utilization, institutionalization, hospitalization and mortality. It is not known whether standard therapies have an effect on such outcomes. Clinical trials enrolling a broad spectrum of elderly patients should be encouraged.
Recommendations: Hospitals and health regions should be strongly encouraged to support the development of specialized heart failure programs, components of which may include in-patient consultation, out-patient clinics and outreach programs. (Class I, Level A)
Educational efforts and interventions are recommended for family physicians to improve the early recognition, detection and diagnosis of heart failure amongst people at increased risk and who present with atypical symptoms. (Class I, Level C)
Initial physical evaluation of each patient requires a detailed medical and social history and careful examination of both non-cardiovascular and cardiovascular signs including supine and erect blood pressure, mobility and exercise tolerance. Initial and ongoing screening for affect, function and cognition is required. In patients with cognitive impairment, education on the management of CHF should be directed at a cognitively intact caregiver. Particular attention must be paid to avoid inappropriate polypharmacy, potential drug interactions and inadvertent aggravation of co-morbid conditions. (Class I, Level C)
Investigations should include an ECG, chest X-ray, Echo or other non-invasive assessment of heart size and function, CBC, electrolytes, renal function and others as indicated by history and physical examination. (Class I, Level C)
Although the elderly have not been the primary focus of most heart failure clinical trials, sub-group analyses suggest that the results of such trials are applicable and current national heart failure guidelines should be applied. (Class I, Level A)
ACE inhibitors, unless contraindicated by angioedema or bilateral renal artery stenosis, are recommended in all patients with heart failure, but can lower blood pressure and should be introduced in very low doses to avoid postural hypotension. The dose should be subsequently increased as tolerated to clinical trial doses. (Class I, Level A)
Angiotensin receptor blockers are recommended in elderly patients with heart failure who are unable to tolerate angiotensin-converting inhibitors because of cough or other side effects. Similar precautions should be applied with regard to renal function and angioedema. (Class I, Level A)
Beta-blockers, unless otherwise contraindicated, are recommended in all patients with symptomatic heart failure, but should be used with greater caution in patients with a past history of syncope or suspected to be at an increased risk of sick sinus syndrome. (Class I, Level A)
Spironolactone is recommended in all patients with severe heart failure without significant renal dysfunction as measured by creatinine clearance, but renal function and serum potassium require close monitoring. (Class I, Level A) Other diuretics are indicated in the lowest doses required to maintain stable weight and symptoms in all heart failure patients who have current or previous fluid retention. (Class I, Level B)
Digoxin is recommended in patients who remain symptomatic in spite of optimized medical therapy including ACE-inhibitors (ARB if appropriate), beta blockade, and adequate diuresis. (Class 1, Level A) Caution must be exercised in the elderly who are at greater risk for digoxin toxicity and its complications, and normal serum digoxin levels should not be relied upon to rule out digoxin toxicity
Patients wishes for quality of living and end of life issues should be established and periodically reviewed as appropriate. (Class 1, Level C)
It is strongly recommended that the appropriate changes in the health care system be implemented to improve appropriate home based care for elderly heart failure patients. (Class 1, Level C)
Research is required to determine whether standard therapies for CHF can maintain functional capacity and cognition in older patients with CHF, as well as prevent institutionalization, hospitalization and reduce mortality (Class 1, Level C).
References
1 Croft JB, Giles WH, Pollard RA, Casper ML, Anda RF, Livengood JR. National trends in the initial hospitalization for heart failure. J Am Geriatr Soc 45; 270-275, 1997.
2 Liu P, Arnold JMO, et al. The 2001 Canadian Cardiovascular Society Consensus Guideline Update for the Management and prevention of Heart Failure. Can J Cardiol 2001 17 Suppl E) 4E-24E
3 Tsuyuki RT, Ackman ML, Montague TJ et al. Effects of the 1994 Canadian Cardiovascular clinical practice guidelines for congestive heart failure. Can J Cardiol 2002; 18:147-152.
4 Heiat A, Gross CP, Krumholz HM. Representation of the elderly, women, and minorities in heart failure clinical trials. Arch Intern Med 2002;162:1682-8.
5 Williamson J, Stokoe IH, Gray S. Old people at home: their unreported needs. Lancet 1964; I: 1117-20.
6 Stuck AE, Siu AL, Wieland GD, Adams A, Rubenstein LZ. Comprehensive geriatric assessment: a meta- analysis of controlled trials.Lancet 1993; 342: 1032-36.
7 Newman AB, Gottdiener JS, McBurnie MA, Hirsch CH, Kop WJ, Tracy R, Walston JD, Fried LP. Associations of subclinical cardiovascular disease with frailty. Journal of Gerontology: Medical Sciences 2001; 56A:M158-M166.
8 Cacciatore F, Abete P, Ferrara N, Calabrese C, Napoli C, Maggi S, Varrichio M, Rengo F. Congestive heart failure and cognitive impairment in an older population. J Am Geriatr Soc 1998; 46:1343-1348.
9 Lindsay J, Hebert R, Rockwood K. The Canadian Study of Health and Aging: risk factors for vascular dementia. Stroke 1997 Mar;28(3):526-30.
10 Burns RB, McCarthy EP, Moskowitz MA, Ash A, Kane RL, Finch M. Outcomes for older men and women with congestive heart failure. J Am Geriatr Soc 1997: 45:276-280.
11 Wolinsky FD, Smith DM, Stump TE, Overhage JM, Lubitz RM. The sequelae of hospitalization for congestive heart failure among older adults. J Am Geriatr Soc 1997; 45:558-563.
12 Fried LP, Guralnik JM. Disability in older adults: Evidence regarding significance, etiology and risk. J Am Geriatr Soc 1997; 45:92-100.
13 Fried LP, Walston J. Frailty and failure to thrive. In: Hazzard WR, Blass JP, Ettinger WH, Halter JB, Ouslander JG, eds. Principles of Geriatric Medicine and Geronotology 4 th Ed. M cGraw-Hill 1999; 1387-1402).
14 Croft JB, Giles WH, Pollard RA, Casper ML, Anda RF, Livengood JR. National trends in the initial hospitalization for heart failure. J Am Geriatr Soc 1997; 45:270-275.
15 Haldeman GA, Croft JB, Giles WH, Rashidee A. Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am Heart J 1999; 137:352-360.
16 Zuccala G, Onder G, Pedone C, Carosella L, Pahor M, Bernabei R. Cocchi A. Hypotension and cognitive impairment: selective association in patients with heart failure. Neurology 2001; 57:1986-1992.
17 Zuccala G, Cattel C, Manes-Gravina E, Di Niro MG, Cocchi A, Bernabei R. Left ventricular dysfunction: a clue to cognitive impairment in older persons with heart failure. J Neurol Neurosurg Psychiatry 1997; 63:509- 512.
18 Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. JAMA 1996; 275:852-857
19 Jarrett PG, Rockwood K, Carver D, Stolee P, Cosway S. Illness presentation in elderly patients. Arch Intern Med 1995; 155:1060-1064.
20 Anderson MA, Pena RA, Helms LB. Home care utilization by congestive heart failure patients: a pilot study. Public Health Nursing 1998; 15:146-162.
21 Vinson JM, Rich MW, Sperry JC, Shah AS, McNamara T. Early readmission of elderly patients with congestive heart failure. J Am Geriatr Soc 1990; 38:1290-1295.
22 Chin MH, Goldman L. Factors contributing to the hospitalization of patients with congestive heart failure. Am J Public Health 1997; 87:643-648.
23 Zuccala G, Onder G, Pedone C, Cocchi A, Carosella L, Cattel C, Carbonin PU, Bernabei R. Cognitive dysfunction as a major determinant of disability in patients with heart failure: results from a multicentre survey. J Neurol Neurosurg Psychiatry 2001; 70:109-112.
24 Ekman I, Fagerberg B, Skoog I. The clinical implications of cognitive impairment in elderly patients with chronic heart failure. J Cardiovasc Nurs 2001; 16:47-55.
25 Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, Redfield MM. Congestive heart failure in the community. A study of all incident cases in Olmstead County, Minnesota, in 1991. Circulation 1998; 98: 2282-2289.
26 Havranek EP, Masoudi FA, Westfall KA, Wolfe P, Ordin DL, Krumholz HM. Spectrum of heart failure in older patients: Results from the National Heart Failure Project. Am Heart J 2002;143:412-417.
27 Rich M Epidemiology, pathophysiology, and etiology of congestive heart failure in older adults. J Am Geriatr Soc 1997;45:968-974.
28 Dauterman KW, Massle BM, Gheoghiade M. Heart6 failure associated with preserved systolic function: A common and costly entity. Am Heart J 1998; 135:S310-S319.
29 Wang R, Mouliswar M, Denman S, Kleban M. Mortality of the institutionalized old-old hospitalized with congestive heart failure. Arch Intern Med 1998; 158:2464-2468.
30 Narain P, Rubenstein LZ, Wieland GD, Rosbrook B, Strome LS, Pietruszka F, Morley JE. Predictors of immediate and 6-month outcomes in hospitalized elderly patients. J Am Geriatr Soc 1988;36:775-783.
31 Blazer DG. Social support and mortality in an elderly community population. Am J Epidemiol 1982; 115:684-694
32 Mossey JM, Shapiro E. Self-rated health: a predictor of mortality among the elderly. Am J Public Health 1982;72:800-808.
33 Idler EL, Kasl SV, Lemke JH. Self-evaluated health and mortality among the elderly in New Haven, Connecticut, and Iowa and Washington counties, Iowa, 1982-1986. Am J Epidemiol 1990;131:91-103.
34 Kostis JB, Davis BR, Cutler J, Grimm RH et al. Prevention of Heart Failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1997; 278:212-216.
35 The ALLHAT Investigators. Major outcomes in high-risk hypertensive patients randomized to angiotensin- converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002 Dec 18;288(23):2981-97.
36 The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992; 327:685-91 37 Rich MW, Shah AS, Vinson JM, Freedland KE, Kuru T, Sperry JC. Iatrogenic congestive heart failure in older adults: Clinical course and prognosis. J Am Geriatr Soc 1996; 44:638-643.
38 Folstein MF, Folstein SE, McHugh PR. Mini mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
39 Scanlon J, Borson S. Te Mini-Cog: receiver operating characteristics with expert and nave raters. Int J Geriatr Psychiatry 2001; 16:216-222.
40 Juby A, Tench S, Baker V. The value of the clock drawing test in identifying executive cognitive dysfunction in people with a normal Mini-Mental State Examination score. Can Med Assoc J 2002; 167:859-864.
41 Michalsen A, Konig G, Thinne W. Preventable causative factors leading to hospital admission with decompensated heart failure. Heart 1998; 80:437-441.
42 Cox NL, Sainsbury P, McLenachan JM, Corrado OJ. Investigatiing heart failure in elderly people: does everyone need an echocardiogram? Age and Aging 1998; 27:291-295.
43 Gottlieb S, Exercise in the geriatric patient with congestive heart failure. AJGC 2001; 10:264-268.
44 Miura T, Kojima R, Sugiura Y, Mizutani M, Takatsu F, Suzuki Y. Effect of aging on the incidence of digoxin toxicity. Ann Pharmacother 2000; 34:427-432).
45 Rich,MW, McSherry F,Williford WO, Yusuf s: Digitalis Investigators Group.J Am
Coll Cardiol 2001 38(3): 806-13
46 The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-533.
47 Rathore SS, Wang Y, Krumholz HM. Sex-Based Differences in the Effect of Digoxin for the Treatment of Heart Failure, N Engl J Med 2002; 347:1403-1411.
48 The CONSENSUS tiral study group. Effects of enalapril on mortality in severe congestive heart failure; results of the Cooperative North Scandanavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316: 1429-1435.
49 The SOLVD Investigators. Effect of enalapril on survival in patients with reduced ejection fractions and congestive heart failure. N Engl J Med 1991; 325:293-302.
50 Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992 Sep 3;327(10):669-677.
51 The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993; 342:821-828.
52 Hutcheon SD, Gillespie ND, Crombie IK, Struthers AD, McMurdo MET. Perindopril improves six minute walking distance in older patients with left ventricular systolic dysfunction: a randomised double blind placebo controlled trial. Heart 2002;88:373-377.
53 Gambassi G, Lapane KL, Sgadari A, Carbonin P, Gatsonis C, Lipsitz LA, Mor V, Bernabei R. Effects of angiotensin-converting enzyme inhibitors and digoxin on health outcomes of very old patients with heart failure. Arch Intern Med 2000;160:53-60.
54 Pitt S, Poole-Wilson PA, Segal r, Martinez FA, Dickstein K, Camm JA, Konstarn MA, Reigger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B. Raandomized trial of losartan versus captopril on mortality in patients with symptomatic heart failure: the losartan heart failure survival study ELITE II. Lancet 2000; 355: 1582-1587.
55 Jong P, Demers C, McKelvie RS, Liu PP. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol 2002; 39:463-470.
56 Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999 Sep 2;341(10):709-717.
57 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31- 41.
58 Mehagnoul-Schipper DJ, Colier WN, Hoefnagels WH, Verheugt FW, Jansen RW. Effects of furosemide versus captopril on postprandial and orthostatic blood pressure and on cerebral oxygenation in patients > or = 70 years of age with heart failure. Am J Cardiol 2002 Sep 15;90(6):596-600.
59 Jansen PA, De Vries OO, De Rooy SE, Raymakers JA. Blood pressure reduction after first dose of captopril and perindopril. J Am Geriatr Soc 2001; 49:1574-1575.
60 Jolobe OM. Evaluation of renal function in elderly heart failure patients in ACE inhibitors. Postgrad Med J 1999; 75:275-277.
61 Heerdink ER, Leufkens HGHerrings RM, Ottervanger JP, Stricker BH, Bakker A. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Int Med. 1998; 158:1108- 1112.
62 Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995;333:1190-5.
63 Chin MH, Wang JC, Zhang JX, Sachs GA, Lang RM. Differences among geriatricians, general internists, and cardiologists in the care of patients with heart failure: a cautionary tale of quality assessment. J Am Geriatr Soc 1998; 46:1349-1354.