Scholarly article on topic 'Cardiac Rehabilitation in Very Old Patients: Data From the Italian Survey on Cardiac Rehabilitation-2008 (ISYDE-2008)--Official Report of the Italian Association for Cardiovascular Prevention, Rehabilitation, and Epidemiology'

Cardiac Rehabilitation in Very Old Patients: Data From the Italian Survey on Cardiac Rehabilitation-2008 (ISYDE-2008)--Official Report of the Italian Association for Cardiovascular Prevention, Rehabilitation, and Epidemiology Academic research paper on "Health sciences"

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Academic research paper on topic "Cardiac Rehabilitation in Very Old Patients: Data From the Italian Survey on Cardiac Rehabilitation-2008 (ISYDE-2008)--Official Report of the Italian Association for Cardiovascular Prevention, Rehabilitation, and Epidemiology"

Journal of Gerontology: MEDICAL SCIENCES

Cite journal as: J Gerontol A Biol Sci Med Sci. 2010 December;65A(12):1353-1361 doi:10.1093/gerona/glq138

© The Author 2010. Published by Oxford University Press on behalf of The Gerontological Society of America.

All rights reserved. For permissions, please e-mail: jouinals.permissiom@oxfordjournals.org.

Advance Access published on July 28,2010

Cardiac Rehabilitation in Very Old Patients: Data From the Italian Survey on Cardiac Rehabilitation-2008 (ISYDE-2008)—Official Report of the Italian Association for Cardiovascular Prevention, Rehabilitation, and

Epidemiology

Francesco Giallauria,1 Carlo Vigorito,1 Roberto Tramarin,2 Francesco Fattirolli,3 Marco Ambrosetti,4 Stefania De Feo,5 Raffaele Griffo,6 and Carmine Riccio7 on behalf of the ISYDE-2008 Investigators of the Italian Association for Cardiovascular Prevention, Rehabilitation, and Prevention

department of Clinical Medicine, Cardiovascular, and Immunological Sciences, Cardiac Rehabilitation Unit, University of Naples

Federico II, Italy.

2Division of Cardiac Rehabilitation, Fondazione Europea di Ricerca Biomedica, Cernusco sul Naviglio, Italy.

3Department of Critical Care Medicine and Surgery, Cardiac Rehabilitation Unit, University of Florence and Azienda

Ospedaliero-Universitaria Careggi, Italy.

4Clinica Le Terrazze, Cunardo, Italy.

5Casa di Cura Polispecialistica Dr. Pederzoli, Peschiera sul Garda, Italy.

6Ospedale La Colletta, Arenzano, Italy.

7Azienda Ospedaliera di Caserta, Italy.

Address correspondence to Giallauria Francesco, MD, PhD, Department of Clinical Medicine, Cardiovascular, and Immunological Sciences, Cardiac Rehabilitation Unit, University of Naples Federico II, Naples, Naples 80131, Italy. Email: giallauria@libero.it

Background. Using data from the Italian SurveY on carDiac rEhabilitation-2008 (ISYDE-2008), this study provides insight into the level of implementation of cardiac rehabilitation (CR) in very old cardiac patients.

Methods. Data from 165 CR units were collected online from January 28 to February 10, 2008.

Results. The study cohort consisted of 2,281 patients (66.9 ± 11.8 years): 1,714 (62.4 ± 9.6 years, 78% male) aged<75 years and 567 aged >75 years (80.8 ± 4.5 years, 59% male). Compared with adults, a higher percentage of older patients were referred to CR programs after cardiac surgery or acute heart failure and showed more acute phase complications and comorbidity. Older patients were less likely discharged to home, more likely transferred to nursing homes, or discharged with social networks activation. Older patients had higher death rate during CR programs (odds ratio = 4.6; 95% confidence interval = 1.6-12.9; p = .004).

Conclusion. The ISYDE-2008 survey provided a detailed snapshot of CR in very old cardiac patients.

Key Words: Cardiac rehabilitation, Elderly—ISYDE 2008 survey—Secondary prevention—Coronary artery disease. Received May 11, 2010; Accepted June 21, 2010 Decision Editor: Luigi Ferrucci, MD, PhD

RANDOMIZED clinical trials have demonstrated that in patients with cardiovascular disease, comprehensive cardiac rehabilitation (CR) improves exercise tolerance, coronary risk factors, psychological well-being, and health-related quality of life and, according to several observational studies or meta-analyses, decreases the risk of new cardiac events (1-5).

In 2006, the Italian National System for Guidelines of the Italian Health Ministry published the Guidelines on Cardiac Rehabilitation and Secondary Prevention, with the endorsement of the Italian Agency of Regional Health Systems (6).

Although the adherence to guidelines has been shown to be associated with improved outcomes, their current implementation in Italy, as in other European countries, remains frequently defective (7-12).

The benefits of CR programs have been well documented in young and middle-aged coronary heart disease patients, whereas older patients are rarely, if ever, included in CR programs and are poorly represented in clinical trials (13-14). On the other hand, one randomized clinical trial did show that CR is at least as effective in older as in adult patients (15). In spite of such evidence, older patients are less likely

to be referred to formal CR programs and, when referred, experience poor program compliance (16,17). The lack of referral to CR programs could be related to a more compromised clinical and functional status of these older patients, who are more likely to present with frailty, higher burden of comorbidities, and disability (18).

Despite epidemiological data show that patients aged 75 years and older requiring cardiac care are increasing, to date, only limited age-specific data are available from observational studies reporting CR in the elderly patients. Most of these data refer to patients with an average patient age <75 years (15,19-21) and from studies of postinfarction CR with small numbers of patients aged >75 years (15,22,23). Nevertheless, several studies have demonstrated that older patients derive similar and sometimes greater relative improvements in exercise tolerance and self-reported physical function in comparison with adult patients after exercise-based CR (23-25).

In the recent past, the Italian Association for Cardiovascular Prevention, Rehabilitation, and Epidemiology (GICR-IACPR) promoted and carried out a detailed observational study of CR programs available in Italy (26,27). The first Italian SurveY on carDiac rEhabilitation (ISYDE)-1999 survey offered an overview of CR services in Italy, illustrating the core components of the existing programs (26). The ISYDE-2008 survey was launched aiming at evaluating whether or not progress had been made in CR practice (27). The broad participation of CR centers throughout Italy and the dimension of surveyed population proved to represent the real, pragmatic rehabilitation world, and clinical profile of patients referred to CR programs.

Because a considerable part of this study cohort consisted of patients >75 years, the present survey aimed at providing an insight in the clinical characteristics and course of a very old population in the real world of CR in Italy.

Methods

Study Design

The multicenter prospective observational study design of the ISYDE-2008 has been described in detail elsewhere (26,27). In summary, the primary purpose of this study was to take a snapshot on current organization, settings, and provision of CR in Italy and to describe the patient population referred to CR, giving a comprehensive and detailed description of clinical characteristics, risk profile, diagnostic procedures, exercise and educational program, discharge modalities, treatment at discharge, and follow-up schedules. The enrolment period lasted from January 28 to February 10, 2008. Data were collected on a web-based case report form, which collected data on clinical characteristics, diagnostic procedures, exercise and educational programs, treatment, and follow-up plans of all the consecutive patients discharged from CR programs in the 2-week study period.

The present study focuses on very old patients (>75 years) compared with the adult population.

Participating Centers

The survey was designed to be carried out in all Italian residential and outpatient CR centers. Centers were invited to participate in the survey on a purely voluntary basis by the executive board of the study and by the regional GICR-IACPR coordinator, who was responsible for interfacing with the investigators in each of the participating centers and overlooked the implementation of the survey protocol. Based on information collected from previous surveys and registries and through an active search of National Health System-authorized facilities carried out at regional level, 208 facilities were identified as potential providers of CR programs and were invited to participate in the study. However, 18 centers were found, on contact, to be inactive or still in a preoperational phase at the time of the study, whereas 25 (13% of the remaining 190) were unwilling or unable to participate. Thus, data collected in the study refer to 165 CR units (87% of all invited facilities). These CR units, representative of national CR organization, were subdivided in 103 (62.4%) residential units, 18 (10.9%) facilities with day hospital care, 33 (20%) facilities with outpatient CR (information not available in 11 [6.7%] CR units). The complete list of ISYDE-2008 investigators and participating centers with names of the director or contact physician is reported in Appendix 1, whereas the updated directory of all Italian Cardiac Rehabilitation Centers of the GICR-IACPR network is available on the official website of the GICR http://www.iacpr.it.

Statistical Analysis

The main analysis was performed subdividing the study cohort into two groups, according to age cutoff of 75 years. Data are expressed as means ± SD or proportions. Comparisons between groups were performed by unpaired t test, c2, or Fisher's Exact Test as required. Correlations between variables were assessed with Pearson's correlation coefficient. Predictors of death were evaluated with multivariate logistic regression analysis. All analyses were performed using SAS (Version 9.1, Cary, NC) with significance set at p < .05.

Results

Table 1 summarizes the demographic characteristics and referral pattern of CR programs in young adult and older study population. The total study cohort consisted of 2,281 patients (66.9 ± 11.8 years, 75% male): 1,714 (75.1%; 62.4 ± 9.6 years, 78% male) aged < 75 years and 567 (24.9%) aged >75 years (80.8 ± 4.5 years, 59% male). Compared with adults, a higher percentage of older patients were

Table 1. Demographics Characteristics and Indications to Cardiac Rehabilitation Programs in Adults and Older Patients

Table 3. Complications During Cardiac Rehabilitation Programs in Adults and Older Patients

<75 years >75years <75 years >75years

4) ,71 = (n = 567) 4) ,71 = £ (n = 567)

n (%) n (%) p Value n (%) n (%) p Value

Male gender 1344 (78.4) 333 (58.7) <.0001 Atrial fibrillation 122 (7.1) 80 (14.1) <.0001

Cardiovascular risk factors* Severe ventricular arrhythmias* 34 (2.0) 9 (1.6) .55

0-2 672 (39.2) 239 (42.1) .21 Definitive pacemaker implantation 9 (0.5) 4 (0.7) .62

3-5 875 (51.0) 284 (50.0) .69 Acute myocardial infarction 7 (0.4) 3 (0.5) .71

>5 167 (9.7) 44 (7.8) .15 Cerebrovascular events* 12 (0.7) 3 (0.5) .66

Indications to cardiac rehabilitation Cognitive impairment 21 (1.2) 22 (3.9) <.0001

Coronary artery surgery 553 (32) 134 (23) <.0001 Anemia* 106 (6.2) 55 (9.7) <.01

Valvular surgery 284 (16) 77 (13) .09 Acute or worsening of chronic 32 (1.9) 39 (6.9) <.0001

Coronary artery + valvular surgery 109 (6.4) 63 (11.1) <.001 kidney disease§

Thoracic aorta surgery 41 (2.4) 13 (2.3) .89 Sternal revision 6 (0.3) 3 (0.5) .55

Acute coronary syndrome 149 (8.7) 52 (9.2) .72 Massive pleural effusion needing 19 (1.1) 13 (2.3) .04

Percutaneous transluminal 269 (15.7) 57 (10.0) <.001 thoracentesis

coronary angioplasty Inotropic support/mechanical 16 (0.9) 7 (1.2) .53

Chronic heart failure 164 (9.6) 121 (21.3) <.0001 assistance

Peripheral artery disease 14 (0.8) 8 (1.4) .20 Respiratory assistance1 20 (1.2) 21 (3.7) <.0001

Other 35 (2.0) 6(1.1) .12 Systemic infections 38 (2.2) 29 (5.1) <.01

Blood transfusions 21 (1.2) 10 (1.8) .34

* Smoking, family history of early coronary heart disease, high blood pres- Others 24 (0.01) 6 (0.01) .88

sure, hypercholesterolemia, body mass index >27, diabetes, sedentary lifestyle,

and early menopause.

referred to CR programs for combined coronary and valvular surgery or after an episode of acute heart failure, whereas a lower percentage of older patients were referred to CR programs after isolated coronary surgery or percutaneous transluminal coronary angioplasty. No differences were observed in cardiovascular risk factors score (including smoking, history, hypertension, dyslipidemia, obesity, diabetes, sedentary lifestyle, and early menopause) between groups.

Table 2. Comorbidities in Adults and Older Patients Referred to Cardiac Rehabilitation Programs

<75 years (n = 1,714)

>75years (n = 567)

n (%) p Value

Previous myocardial infarction 377 (22.0) 126 (22.2)

Previous percutaneous transluminal 170 (9.9) 55 (9.7)

coronary angioplasty

Previous cardiac surgery 180 (10.5) 70 (12.3)

Carotid arteries atherosclerosis* 97 (5.6) 63 (11.1)

Symptomatic peripheral artery disease* 98 (5.7) 53 (9.3)

Chronic obstructive pulmonary disease 192 (11.2) 106 (18.7)

Chronic respiratory insufficiency* 60 (3.5) 52 (9.2)

Chronic kidney disease§ 103 (6.0) 97 (17.1)

Stroke 50 (2.9) 33 (5.8)

Cognitive impairment 24 (1.4) 40 (7.1)

Gastroesophageal disease 78 (4.5) 40 (7.1)

Diabetes 339 (19.8) 136 (24.0)

Cancer 57 (3.3) 26 (4.6)

Orthopedic/joints/immune-related 129 (7.5) 78 (13.8) disease

.22 <.0001 <.01 <.0001 <.0001 <.0001 .001 <.0001 .02 .03 .16 <.0001

* Stenosis >70% or previous revascularization.

* Fontaine stage >1 or previous revascularization.

* Long-term oxygen therapy. § Creatinine >1.5 mg/dL.

* >30 s or symptomatic ventricular tachycardia.

* Stroke, transient ischemic attack.

* Hb <10 g/dL or >3 g/dl reduction with respect to the preindex event value.

§ Creatinine >2.5 mg/dL when preindex event value <1 mg/dL or creatinine

increase >1 mg/dL in patients with previous chronic kidney disease.

1 Including oxygen therapy, mechanical ventilation, continuous positive airway pressure, bilevel positive airway pressure >96 h.

Older patients showed a greater frequency of comorbidities (Table 2), such as critical stenosis of carotid arteries and peripheral artery disease, chronic obstructive pulmonary disease, chronic kidney disease, neurological sequelae after stroke or cognitive impairment, gastroesophageal disease, diabetes, and orthopedic/joints/immune-related disease.

During CR programs, a higher percentage of older patients developed complications as persistent atrial fibrillation (AF), cognitive impairment, and acute kidney disease or worsening of chronic kidney disease (Table 3). Other complications, particularly frequent in older patients, were anemia, systemic infections, massive pleural effusion requiring thoracentesis, and acute respiratory insufficiency with need for respiratory assistance.

Differences between older and adult patients were also detected in the access to diagnostic procedures during CR. Older patients less frequently underwent diagnostic procedures, such as exercise and cardiopulmonary stress testing on admission or at discharge, whereas no difference was observed in the performance of 6-minute walking test (6MWT) (Table 4). As many as 275 older patients (48%) received no physical performance test (6-minute walking test, exercise stress testing, or cardiopulmonary exercise testing); this proportion was significantly greater than in adult patients (34%, p < .0001). Compared with adults, older patients not performing any physical performance testing showed a higher percentage of comorbidities, such as respiratory insufficiency (58% vs 41%, p < .0001),

Table 4. Diagnostic and Therapeutic Procedures During Cardiac Rehabilitation Programs in Adults and Older Patients

Table 5. Educational and Psychological Interventions Performed During Cardiac Rehabilitation Programs in Adults and Older Patients

<75 years (n = 1,714)

>75years (n = 567)

p Value

6-min walking test on admission 749 (43.7) 234 (41.3) .31

6-min walking test at discharge 705 (41.1) 242 (42.7) .52

Exercise stress testing on admission 388 (22.6) 58 (10.2) <.0001

Exercise stress testing at discharge 619 (36.1) 86 (15.2) <.0001

Cardiopulmonary exercise stress 106 (6.2) 16 (2.8) <.01

testing on admission

Cardiopulmonary exercise stress 138 (8.0) 19 (3.3) <.001

testing at discharge

Echocardiography (n) 1509 (88.0) 513 (90.5) .11

Electrocardiogram telemetry >72 h 500 (29.2) 194 (34.2) .02

Venous infusions 137 (8.0) 102 (18.0) <.0001

Geriatric multidimensional 308 (18.0) 146 (25.7) <.0001

evaluation

Computed tomography 58 (3.4) 31 (5.5) .03

Ultrasounds 260 (15.2) 114 (20.1) <.01

Group exercise sessions 1396 (81.4) 399 (70.4) <.0001

Individual exercise sessions 369 (21.5) 218 (38.4) <.0001

chronic kidney disease (53% vs 46%, p < .0001), and cognitive impairment (66% vs 33%, p < .0001), and a higher percentage of complications during the CR program, such as cognitive deterioration (65% vs 34%, p = .0005), kidney failure (63% vs 37%, p < .0001), and need of inotropic support or mechanical assistance (65% vs 35%, p = .001). Echocardiography showed a lower percentage of older patients with preserved left ventricular ejection fraction (LVEF>50%) compared with adult patients (50.3% vs 61.7%, p < .0001, respectively).

Educational and psychological interventions were more frequently not performed in older patients compared with adult patients (Table 5). Particularly, older patients received less general information on cardiovascular risk factors, diet, physical activity, smoking cessation, drug management, and psychological intervention. On the other hand, they more often received information on chronic heart failure (CHF) (Table 5).

At discharge, compared with young adult patients, elderly patients were more frequently prescribed with nitrates, diuretics, digitalis, amiodarone, antihypertensive drugs other than ACE-I or ARB, antidepressants and heparin, and less frequently with beta blockers, aspirin, omega-3 fatty acids, statins, and ezetimibe (Table 6).

Older patients had a significantly longer hospital length of stay (19 ± 9 vs 18 ± 10 days, p = .009) and less accesses to the day hospital care (13 ± 9 vs 16 ± 9 days, p = .04) or to outpatient clinic (4 ± 9 vs 15 ± 9 days, p = .0008), despite a longer length of clinical supervision (123 ± 153 vs 81 ± 120 days, p = .013). Older patients were less likely to be discharged home (88% vs 92%, p = .004) and, rather, more likely to be transferred to nursing homes (1.1% vs 0.1%, p = .001) or discharged with social assistance networks activation (0.5% vs 0.06%, p = .02).

<75 years (n = 1,714) n (%) >75years (n = 567) n (%) p Value

General information on risk factors

None 48 (2.8) 50 (8.8) <.0001

Group 893 (52.1) 267 (47.0)

Individualized 359 (20.9) 136 (24.0)

Both 414 (24.1) 114 (20.1)

None 131 (7.6) 87 (15.3) <.0001

Group 783 (45.7) 238 (42.0)

Individualized 491 (28.6) 149 (26.3)

Both 309 (18.0) 93 (16.4)

Physical activity

None 57 (3.3) 49 (8.6) <.0001

Group 1020 (59.5) 262 (46.2)

Individualized 252 (14.7) 116 (20.5)

Both 385 (22.5) 140 (24.7)

Smoking

None 1006 (58.7) 426 (75.1) <.0001

Group 431 (25.1) 98 (17.3)

Individualized 157 (9.2) 17 (3.0)

Both 120 (7.0) 26 (4.6)

Drug therapy management

None 160 (9.3) 101 (17.8) <.0001

Group 285 (16.6) 74 (13.0)

Individualized 1031 (60.1) 322 (56.8)

Both 238 (13.9) 70 (12.3)

Oral anticoagulant therapy management

None 1166 (68.0) 367 (64.7) .35

Group 140 (8.2) 53 (9.3)

Individualized 311 (18.1) 118 (20.8)

Both 97 (5.7) 29 (5.1)

Diabetes

None 1041 (60.7) 351 (62.0) .23

Group 279 (16.3) 78 (13.8)

Individualized 253 (14.8) 98 (17.3)

Both 141 (8.2) 40 (7.0)

Heart failure

None 1171 (68.3) 334 (58.9) <.0001

Group 262 (15.3) 86 (15.2)

Individualized 163 (9.5) 102 (18.0)

Both 118 (6.9) 45 (7.9)

Psychological intervention

None 576 (33.6) 248 (46.7) <.0001

Group 432 (25.2) 115 (20.3)

Individualized 332 (19.4) 110 (19.4)

Both 374 (21.8) 94 (16.6)

Finally, very old patients had an increased death rate during CR program compared with the adult cohort (9/567 vs 6/1714, p = .002, respectively).

Bivariate analysis showed that the occurrence of AF during the CR program (r = .05, p = .01), respiratory insufficiency (r = .08, p < .0001), acute kidney failure (r = .05, p = .01), and stroke or cognitive impairment (r = .04, p = .04) were significant predictors of death.

Multivariate logistic analysis showed that developing AF during CR programs (odds ratio = 3.5, 95% confidence interval = 1.1-11.3, p = .03), and respiratory insufficiency

Table 6. Drug Therapy at Hospital Discharge After Cardiac Rehabilitation Programs in Adults and Older Patients

<75 years (n = 1,714)

>75 years (n = 567)

n (%) n (%) p Value

Inhibitors of 947 (55.2) 310 (54.7) .81

angiotensin-converting enzyme

Angiotensin II receptor blockers 283 (16.5) 104 (18.3) .31

Beta blockers 1233 (72.0) 333 (58.7) <.0001

Nitrates 304 (17.7) 136 (24.0) <.01

Diuretics 777 (45.3) 391 (69.0) <.0001

Statins 1180 (68.8) 330 (58.2) <.0001

Fibrates 7 (0.4) 1 (0.2) .42

Omega-3 fatty acids 314 (18.3) 64 (11.3) <.0001

Oral anticoagulant therapy 440 (25.7) 164 (28.9) .13

Aspirin 1169 (68.2) 339 (59.8) <.001

Other antiplatelet drug 421 (24.6) 120 (21.2) <.001

Digitalis 78 (4.5) 46 (8.1) <.001

Amiodarone 84 (4.9) 48 (8.5) <.01

Calcium channel blockers 315 (18.4) 121 (21.3) .12

Other antihypertensives 57 (3.3) 37 (6.5) <.001

Insulin 156 (9.1) 55 (9.7) .67

Oral hypoglycemic drugs 263 (15.3) 90 (15.9) .76

Antidepressant 90 (5.2) 51 (9.0) <.001

Antiarrhythmics 29 (1.7) 12 (2.1) .51

Heparin 31 (1.8) 23 (4.1) <.01

(odds ratio = 5.5, 95% confidence interval = 1.4-22.3, p = .01) were significant predictors of death.

Discussion

To the best of our knowledge, our study, by deriving data from the 2008 ISYDE survey, is the first to explore in such depth the characteristics of the "real world" CR patients aged >75 years admitted to CR programs in Italy.

Although exercise-based CR is recognized as an essential component in the contemporary management of patients with heart disease, including the older, admission to CR and secondary prevention programs has been estimated at only~20% for older eligible patients (13-15). Therefore, poor participation and adherence represent a critical problem for assuring the best treatment to older patients after an acute cardiac event (15,19-21,23). Furthermore, in the majority of these studies, the representation of patients older than 75 years, the "real world" old patients, has been poor or difficult to evaluate.

Several cultural, economic, logistic, and organization barriers to patient referral and subsequent program entry and adherence have been recognized The strength of the primary care physician's referral to CR seems one of the most powerful predictor of subsequent participation (14-16).

The present survey revealed that 59% of patients admitted to CR are aged >65 years and that 25% are aged >75 years. Overall, roughly half of the very old patients were enrolled in CR after cardiac surgery, reflecting the increased trend of older patients undergoing cardiac surgery in Italy

(28) and the decline in operative mortality due to increased surgical experience and to improvement of surgical strategies (29), despite very old patients are at higher risk (30). Therefore, in the light of our data, we can conclude that in Italy, there is an increasing trend to include older patients into CR programs, despite their higher clinical risk profile.

Interestingly, heart failure was the second only to cardiac surgery as indication to CR in very old patients, more than twice that was observed in the adults cohort. This may reflect the higher prevalence of CHF in the very elderly patients (31), due to the increased severity and complexity of cardiac disease, associated with higher frequency of comorbidities, in particular respiratory and renal insufficiency, that may easily precipitate an acute episode of heart failure in this age population (32).

The lower percentage of very old patients enrolled into CR after percutaneous coronary angioplasty may reflect a low reliance on secondary prevention programs in the very old, despite evidence of their effectiveness even in the very advanced age range (14-17).

In line with previous literature data (17,33,34), this survey confirmed in older patients the large burden of comor-bidities. This might also explain the higher frequency of complications occurring both during the acute phase of hos-pitalization for the acute event and/or during CR.

Our study yields insights on AF, the most common arrhythmia seen in older cardiac patients. Although physical activity has been reported to increase the risk of AF (35), we do not believe that the onset of physical activity within the CR program could have been responsible for a higher AF frequency during this period because greater leisure-time activity and walking are rather associated with lower incidence of AF, and conversely, intensity of exercise had a U-shaped relationship with AF, with lower risk among individuals exercising with moderate, but not high, intensity (36).

Acute kidney disease occurred more frequently in older patients during CR programs compared with the adult cohort. This might be the consequence of a diffused atherosclerotic process and/or impaired renal blood flow due to heart failure.

Diagnostic procedures were underused in very old patients undergoing CR programs. In particular, compared with adults, a larger proportion of older patients did not perform any type of physical performance test. These findings might reflect a more compromised physical status or level of disability preventing older patients to perform exercise stress testing or might be due to the more frequent comor-bidities with relative contraindication. This might have prognostic relevance because the lack of referral to exercise stress testing is by itself a negative prognostic indicator after an acute cardiac event (37). Interestingly, no differences among age groups were found in the use of 6-minute walking test, which requires lower aerobic performance and therefore was preferentially adopted in the evaluation of

very old patients. In this survey, age-associated physical disability is also revealed by the great number of tailored physical therapy interventions performed by very old patients, who required individual attention rather than group session. It is also well known that disability is inversely correlated with aerobic capacity and depression in older coronary artery disease patients (38). However, we could not exclude that some of the lower referral to performance test was due to physical fear or choice by physician rather than to the real functional status of the older patient.

Educational interventions focused on physical therapy were less frequently provided to very old patients compared with the adult cohort. Again, this might be the consequence of bias toward a perceived reduced efficacy of secondary prevention in this age range but also to the more frequent mental deterioration or use of antidepressant drugs in very old patients (39). Conversely, information on drug therapy was more frequent in older patients, who are often on polypharmacological regimens, at a higher risk of iatrogenic complications; also psychological interventions were more frequent, likely due to the higher prevalence of depression in this population (40).

The present survey revealed also interesting differences relatively to drugs use. In agreement with literature data (40), older patients were discharged by CR Units with fewer indications to beta blockers, statin, and antiplatelet drugs compared to adult patients, thus confirming the difficulties of adopting in the real clinical world and in very old patients the recommendations of international guidelines regarding secondary prevention (14-17).

Finally, mortality during CR in very old patients was higher compared with the adult cohort, possibly reflecting the higher clinical risk profile of this very elderly cohort rather than indicating adverse effects of CR program. In fact, we do not have a control group of >75-year-old patients not enrolled in CR programs, where mortality could have been even higher. The development of AF and respiratory insufficiency was the most significant predictor of death during CR programs, independently of age and other comorbidities.

The major limitation of the present study was the lack of reporting some important functional and clinical parameters of possible interest; this was due to the short-term survey characteristics of the study, which collected the essential data in order to characterize the demographic and clinical course of the patients. However, the survey successfully highlighted crucial differences in the very old patient population entering CR programs in Italy.

In conclusion, this study shows in a large population the differences in access, clinical presentation, and course of very elderly patients entering CR programs. In the research agenda, studies are needed in order to identify the best strategies for expanding referral to CR in very old patients, fostering the application of tailored functional evaluation, educational intervention, appropriate drug treatment, and adherence to secondary prevention guidelines, with the aim of reducing in-hospital complica-

tions and improving functional recovery, long-term mortality, morbidity, and quality of life in this very elderly population of patients.

Funding

No funding sources had any role in the study design, conduct, data collection, analysis, data interpretation, or writing of this report. The GICR-IACPR coordinated the study, managed the data, and undertook all analyses. All members of the scientific board and writing committees had full access to the database and assumed final responsibility for the results submitted for publication.

Acknowledgment

We are deeply indebted to Prof. Mauro Di Bari (Department of Critical Care Medicine and Surgery, Unit of Geriatrics, University of Florence and Azienda Ospedaliero-Universitaria Careggi) for his careful statistical revision of this manuscript.

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Appendix i

ISYDE-2008 Study Investigators

Scientific Board

R. Tramarin (Cernusco S/N, MI), R. Griffo (Arenzano, GE), C. Riccio (Caserta), R. Carlon (Cittadella, PD), A. Castello (Palermo), M. Ferratini (Milano), C. Schweiger (Milano), C. Chieffo (Napoli), and C. Vigorito (Napoli).

Writing Committee

R. Tramarin (Cernusco S/N, MI), C. Vigorito (Napoli), F. Giallauria (Napoli), M. Ambrosetti (Cunardo, VA), S. De Feo (Peschiera del Garda, VR), R. Griffo (Arenzano, GE), M. Piepoli (Piacenza), and C. Riccio (Caserta).

Executive Committee

M. Ambrosetti (Cunardo, VA), S. De Feo (Peschiera del Garda, VR), T. Diaco (Rivolta d'Adda, CR). Delegati Regionali del Gruppo Italiano di Cardiologia Riabilitativa e Preventiva: Abruzzo: C. Ciglia (Chieti), Basilicata: A. Lapolla (Policoro, MT), Calabria: F. Pietropaolo (Soriano Calabro,VV), Campania: G. Furgi (Telese Terme, BN), Friuli Venezia Giulia: G. Martin (Sacile, PN), Emilia Romagna: P. Semprini (Rimini), Lazio: A. Avallone (Roma), Liguria: D. Bertoli (Sarzana, SP), Lombardia: T. Diaco (Rivolta d'Adda, CR), Marche: R. Belardinelli (Ancona), Piemonte: F. Soffiantino (Lanzo Torinese, TO), Puglia: D. Scrutinio (Cassano Murge, BA), Sardegna: P. Maxia (Cagliari), Sicilia: R. Coco (Catania), Toscana: C. Giustarini (Volterra, PI), Umbria: P. Anniboletti (Perugia), Veneto: G. Favretto (Motta di Livenza, TV).

Technical Support

P. Vaghi (Saronno), P. Calisi (Arenzano, GE), C. Chia-vetta (Genova), Aristea S.p.A. (Genova), Segno & Forma S.p.A. (Milano)

ISYDE-2008 Investigators (Italian regions in bold)

Abruzzo: Leonello Guarracini, Presidio Ospsaledaliero Tagliacozzo, Tagliacozzo; Carlo Ciglia, Casa di Cura Villa Pini D'Abruzzo, Chieti; Giorgio, Marcellini, Presidio Os-pedaliero S. Omero, S. Omero. Calabria: M. Iannopollo, Presidio Ospedaliero Siderno, USL 9 Locri (RC), Siderno; Gennarino Borrello, Azienda Ospedaliera Mater Domini, Catanzaro; Milena Matta, Presidio Ospedaliero di Cetraro, Cetraro; N. Peccerillo, Ospedale di Mormanno, ASL 2 Cas-trovillari, Mormanno; Franco Boncompagni, Ospedale dell'Annunziata, Cosenza; Achille Amici, Casa di Cura "San Francesco," Mendicino (CS), Mendicino; Francesco Pietropaolo, Presidio Ospedaliero, Soriano Calabro; Emi-dio Feraco, IRCCS INRCA, Cosenza; G. Pulitano, Presidio Ospedaliero Policlinico Madonna della Consolazione, Reg-gio Calabria; Ermete Tripodi, ASP 5 Regione Calabria, Scilla. Campania: Giuseppe Furgi, IRCCS Fondazione Salvatore Maugeri, Telese Terme; Carmelo Chieffo, Casa di Cura Clinical Center, Napoli; Soccorso Capomolla, Presidio Ospedaliero Polispecialistico Don Gnocchi Onlus, Sant'Angelo dei Lombardi; Paolo Golino, Azienda Os-pedaliera di Caserta, Dipartimento di Cardiologia, Caserta; Gennaro Parrilli, Campolongo Hospital S.p.A. Casa di Cura, Eboli; Antonio Di Patria, Casa di Cura Villa delle Magnolie, Castel Morrone; Claudio Di Gioia, Casa di Cura Privata Villa Margherita, Istituto S. Giuseppe Moscati, Benevento; Domenico Micieli, Azienda Ospedaliera V. Monaldi, Napoli; Carlo Vigorito, Azienda Universitaria Policlinico, Universita di Napoli Federico II, Napoli; Silvio Perrotta, ASL Napoli 1, Napoli; Alessandro Rubino, Azienda S. G. MoscatiAvellino; Vincenzo Aulitto, Centro Serapide S.p.A., Pozzuoli; Gerardo Riccio, Ospedale di Nocera, Nocera Inferiore. Emilia Romagna: Luciano Codec, Azienda Universitaria Ospedale S. Anna, Ferrara; Paolo Coruzzi, Fondazione Don Carlo Gnocchi, Onlus, Parma; Enrico Violi, Azienda Ospedaliera di Reggio Emilia, Castelnovo Monti; Massimo Nardini, Ospedale Regina Margherita, Castelfranco Emilia; Stefano Urbinati, Azienda USL di Bologna, Bologna; Sylvia Dcruz, Casa di Cura Pri-vata ad Indirizzo Riabilitativo San Giacomo srl, Ponte dell'Olio; Pierluigi Semprini, Ospedale Infermi Rimini, Rimini; Massimo Piepoli, Azienda Unita Sanitaria Locale di Piacenza, Piacenza; Alessandro Fucili, Ospedale Sant'Anna, Ferrara; Massimo Cerulli, Ospedale Privato Accreditato Villa Pineta, Gaiato di Pavullo N/F; Bini Roberto, Azienda USL Cesena, Cesenatico; Guido Balestra, Villa Maria Cecilia Hospital, Cotignola. Friuli Venezia Giulia: Dulio Tuniz, IMFR Udine, ASS N. 4, Udine; Giovanni Martin, Azienda Ospedaliera Santa Maria degli Angeli Pordenone, Sacile; Pierpaolo Gori, Casa di Cura Pineta del Carso, Aurisina; Roberto Marini, ASS N. 2 Ison-tina, Gorizia; Tullio Morgera, Ospedale San Polo, Monfalcone. Lazio: Franco Di Mario, Istituto Clinico Riabilitativo Villa delle Querce, Nemi; Maurizio Volterrani,

IRCCS San Raffaele Pisana, Roma; Alfonso Galati, Presidio Ospedaliero Santo Spirito, Presidio Villa Betania, ASL Roma E, Roma; Alessandro Salustri, Policlinico Luigi Di Liegro, Roma; Anna Patrizia Jesi, Presidio Ospedaliero Salus Infirmorum, Roma; Augusto Lacch, Azienda Ospedaliera San Camillo, Forlanini, Roma; Francesco Loperfido, Complesso Integrato Columbus. Universita Cattolica del Sacro Cuore, Roma. Liguria: Luca Corsiglia, Istituto Cardiovascolare Camogli, Ruta di Camogli; Raffaele Griffo, ASL 3 Genovese, Arenzano; Paolo Pantaleo, Strut-tura Ospedaliera Privata Accreditata Villa Azzurra, Rapallo; Guido Gigli, Regione Liguria ASL 4, Centro Regionale di Riabilitazione Cardiologica, Sestri Levante; Daniele Bertoli, ASL 5 Spezzino, Sarzana. Lombardia: Diego Marchesi, Clinica Domus Salutis Ancelle della Carita, Brescia; Oreste Febo, IRCCS Fondazione Salvatore Maugeri, Montescano; Franco Cobelli, IRCCS Fondazione Salvatore Maugeri Pavia, Pavia; Claudio Malinverni, Azienda Ospedaliera "Bolognini," Seriate; Maurizio Fer-ratini, Fondazione Don Gnocchi Onlus, Milano; Norman Jones, Ospedale Trabattoni Ronzoni, Seregno; Claudio Anza, Multimedica Holding, Presidio Ospedaliero di Cas-tellanza, Castellanza; R. Frizzelli, Azienda Ospedaliera C. Poma di Mantova, Bozzolo; Paolo Gei, Spedali Civili di Brescia, Gardone Riviera; Flavio Acquistapace, Policlinico di Monza, Monza; Roberto Pedretti, IRCCS Fondazione Salvatore Maugeri, Tradate; Roberto Tramarin, Fondazione Europea di Ricerca Biomedica, Onlus, Cernusco S/N, Milano; Stefano Carugo, Centro di Cardiologia Riabilitativa, Pio Albergo Trivulzio, Milano; Gabriella Malfatto, Istituto Auxologico Italiano IRCCS, Milano; Tommaso Diaco, Azienda Ospedale Maggiore di Crema, Rivolta D'Adda; Marco Ambrosetti, Clinica Le Terrazze, Cunardo; Carlo, Meloni, Ospedale San Raffaele IRCCS U.O. Riabilitazione Cardiaca, Milano; Amerigo Giordano, IRCCS Fondazione Salvatore Maugeri, Lumezzane; Alberto Schizzarotto, Azienda Ospedaliera S. Antonio Abate di Gallarate, Somma Lombardo; Renzo Zanettini, Azienda Ospedaliera Istituti Clinici di Perfezionamento, Milano; Roberto Bosco, Ospedale Romano di Lombardia, Romano di Lombardia; Giuseppe Occhi, Azienda Ospedaliera della Valtellina e Valchiavenna, Sondalo; Stefano Aglieri, Istituto Clinico Humanitas, Rozzano; Giuseppe Caprioli, Humanitas, Clin-iche Gavazzeni S.p.A., Bergamo; Nicola Cuocina, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo; Luciano Lazzaroni, Aurelio Lorenzi, Centro di Cardiologia Riabilitativa di Cesano Boscone, Casa di Cura Ambrosiana, Cesano Boscone; Cinzia Savonelli, Cof Lanzo Hospital S.p.A. Clinica Ortopedica e Fisiatrica, Lanzo D'Intelvi; Marco Veniani, Azienda G. Salvini Garbagnate Milanese, Rho; Giovanni Corda, Azienda Ospedaliera ed Universitaria: Ospedale di Circolo ed Universita dell'Insubria, Varese, Cuasso al Monte; Claudia Meinecke, Azienda Istituti Ospitalieri di Cremona, Cremona; Giuseppe Castiglioni, ASL Prov. Milano, Presidio Ospedaliero Cassano D'Adda,

Cassano D'Adda; Ravizza Pierfranco, Azienda Ospedaliera Ospedale di Lecco, Merate; Paolo Giani, Fondazione Europea di Ricerca Biomedica Onlus, Trescore Balneario; Fabio Robustelli della Cuna, Ospedale di Morbegno, ASL Provincia di Sondrio, Morbegno; Giuseppe Gullace, Azienda Provinciale Ospedale di Lecco, Lecco; Federico Passoni, Azienda Ospedaliera di Legnano, Cuggiono; Maria Vittoria Barelli, Centro Fisioterapico Riabilitativo Club Francesco Conti, Milano; Italo Richichi, Ospedale San Matteo U.O. di Riabilitazione, Belgioioso; Angelo Rossi, Casa di Cura Villa Esperia, Salice Terme; Alessandro Politi, Ospedale Generale di ZonaGravedona. Marche: Romualdo Belardi-nelli, Azienda Ospedaliero, Universitaria Umberto I, An-cona; Casa di Cura Villa Serena, Jesi; Mauro Persico, ASUR Marche Zona Territoriale 12, San Benedetto del Tronto, Area Vasta N. 5, San Benedetto del Tronto. Piemonte e Valle d'Aosta: Pantaleo Giannuzzi, IRCCS Fondazione Salvatore Maugeri, Clinica del Lavoro e della Riabilitazione, Veruno; Gianmauro Mazzucco, Casa di Cura Villa Serena, Centro Medico di Riabilitazione Cardiologica e Pneumologica, Piossasco; Enzo Bosimini, Casa di Cura Major, Sede Distaccata IRCCS Fondazione Maugeri Veruno, Torino; Giuseppe Riva, Casa di Cura Riabilitativa Stella del Mattino, Boves; Francesco Soffiantino, Presidio Ospedaliero di Lanzo, Lanzo Torinese; Nicola Massobrio, Ospedale Evangelico Valdese di Torino, Torino; Luca Gon-doni, Unita Operativa ad indirizzo Cardiologico, IRCCS Istituto Auxologico Italiano, Piancavallo di Oggebbio; Franco Aina, Azienda Ospedaliero-Universitaria Ospedale Maggiore della Carita di Novara, Novara; Biagio Ingignoli, Ospedale Ss Trinita, Fossano; Maria Vincenza Cal, Osped-ale di Acqui Terme, Acqui Terme; Aillon Costante, Azienda USL Valle D'Aosta, Ospedale Regionale "Umberto Pa-rini," Aosta. Puglie: Domenico Scrutinio, IRCCS Fondazione Salvatore Maugeri, Cassano Murge; Massimo Villella, IRCCS Casa Sollievo della Sofferenza, San Giovanni Ro-tondo; Concetta La Rosa, Casa di Cura Villa Verde snc, Taranto. Sardegna: Luigi Sannia, ASL Sassari, Sassari. Sicilia: Paolo Barbanto, Presidio Ospedaliero M. Ascoli, S. Tommaselli, Azienda Ospedaliera, Catania; Antonio Castello, Ospedale Buccheri La Ferla Fatebenefratelli, Palermo; Rosario Coco, Azienda Ospedaliera Cannizzaro, Dipartimento Cardiovascolare, Catania; Renato Rametta, Azienda Ospedaliera "San Giovanni di Dio," Agrigento; Daniele Albanese, Unita di Valutazione Funzionale e Riabilitazione del Cardiopatico, Ospedale Civico A.R.N.A.S., Palermo; Antonio Circo, Casa di Cura Carmide Villa l'Ulivo, Catania; Rosaria Raciti, Centro Cuore Morgagni, Pedara; Luigi Scarnato, Casa di Cura Regina Pacis, San Cataldo; Flavia Dispensa, Fondazione Istituto San Raffaele

Giglio, Cefalu; Leondardo La Spina, Centro Ionico di Cardiologia, Riposto; Alfio Stuto, Star For Life c/o Poliam-bulatorio di Cardiologia Dr. Armaro Biagio s.a.s., Siracusa; Calogero Vasco, Azienda Ospedaliera Umberto I, Enna; Salvatore Gibiino, Diagnostica Cardiovascolare del Dr. S. Gibiino & C. snc., Catania; Michele Gabriele, Ospedale di Mazara Del Vallo, Mazara Del Vallo; Claudio Dispensieri, Azienda Ospedaliera Piemonte, Messina; Vittorio Carini, Casa di Cura Riabilitativa "Villa Sofia," Acireale. Toscana: Michele Provvidenza, ASL 12 Versilia, Presidio Ospedaliero di Viareggio, Lido di Camaiore; Alessandro Scalzini, ASL 6 Livorno, Presidio Ospedaliero di Cecina, Cecina; Carlo Giustarini, Auxilium Vitae Volterra S.p.A., Volterra; Claudio Macchi, Fondazione Don Gnocchi Onlus, IRCCS, Impruneta; Francesco Fattirolli, Azienda Os-pedaliero Universitaria Careggi, Firenze; Mauro Vannucci, IFCA Villa Ulivella e Glicini, Firenze; Luciana Iacopetti, ASL 3 Pistoia, Presidio Ospedaliero Pescia, Pescia; Mario Cordoni, ASL 6 Livorno, Presidio Ospedaliero di Piom-bino, Piombino. Trentino e Alto Adige: Ferrario Gabriele, Casa di Cura Eremo, Arco; Renato Santoni, Ospedale Clas-sificato San Pancrazio, Arco; Walter Pitscheider, Centro di Riabilitazione del Cardiopatico, Salus Center, Bolzano; Roberto Bettini, Ospedale di Trento, Mezzolombardo; Daniela Girardini, S. Maria del Carmine, Rovereto, Centro di Riabilitazione Cardiologica Ospedale di Ala, Ala. Umbria: Sara Mandorla, ASL 1, Gualdo Tadino, Gualdo Tadino; Fabrizio Anniboletti, ASL 2 Servizio di Cardiologia Ex Ospedale Grocco Perugia, Perugia; Federico Patri-archi, UO Cardiologia Ospedale di Foligno, Nocera Umbra. Veneto: Giuseppe Favretto, Ospedale Riabilitativo di Alta Specializzazione S.p.A., Motta di Livenza; Pier Luigi Bar-oni, Casa di Cura Villa Garda, Garda; Fede Bordin, ASL N. 4, Presidio Ospedaliero di Thiene, Thiene; Pietro Biondi, ULSS 8, Montebelluna; Fabio Bellotto, Istituto Riabilitativo, Cortina D'Ampezzo; Albino Zanocco, Azienda Ospedaliera, Mirano; Andrea Ponchia, ULSS 16, Padova; Enzo Mantovani, Azienda ULSS 15, Camposampiero; Ennio Li Greci, Ospedale Don L. Chiarenzi, AALSS 21 Legnago (Verona), Zevio; Roberto Carlon, Azienda ALSS 15 Presidio Ospedaliero di Cittadella, Cittadella; Leopoldo Celegon, UO di Cardiologia, Riabilitazione Cardiologica, Castelfranco Veneto; Stefano Baracchi, Ospedale al Mare Lido di Venezia, Lido di Venezia; Grazia Pizzolato, AUSSL N. 10, San Dona di Piave; Lorenzo Peroni, Policlinico San Marco, Mestre; Enzo Apolloni, Ospedale di Asiago, Asiago; Gianmarco Mosele, Casa di Cura Privata Villa Margherita S.r.l., Arcugnano; Mario Guarnerio, Ospedale di Feltre, Feltre; Loris Roncon, Ospedale di Rovigo, Rovigo.