Impact of Frailty and Functional Status on Outcomes in Elderly Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Angioplasty: Rationale and Design of the IFFANIAM Study

Abstract

The IFFANIAM study (Impact of frailty and functional status in elderly patients with ST segment elevation myocardial infarction undergoing primary angioplasty) is an observational multicenter registry to assess the impact of frailty and functional status on outcomes of elderly patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary angioplasty. STEMI patients age 75 years or older undergoing primary angioplasty will be extensively studied during admission in 4 tertiary care Hospitals in Spain, assessing their baseline functional status (Barthel index, Lawton‐Brody index), frailty (Fried criteria, FRAIL scale [fatigue, resistance, ambulation, illnesses, and loss of weight]), comorbidities (Charlson index), nutritional status (Mini Nutritional Assessment–Short Form), and quality of life (Seattle Angina Questionnaire). Participants will be managed according current recommendations. The primary outcome will be the description of 1‐year mortality, its causes, and associated factors. Secondary outcomes will be functional capacity and quality of life. Results will help to better understand the impact of frailty and functional ability on outcomes in elderly STEMI patients undergoing primary angioplasty, thus potentially contributing to improving their clinical management. Higher life expectancy has resulted in a large segment of elderly population and an increase in myocardial infarction in these patients. This calls attention to healthcare systems to focus on promoting methods to improve the clinical management of this population.

Introduction

Cardiovascular disease is a major cause of morbidity and mortality in elderly patients. The incidence of myocardial infarction (MI) increases with age and is particularly high in the elderly.1 In addition, comorbidities and frailty are common in this clinical setting and are associated with higher rates of complications, longer hospital stay, and consumption of healthcare resources.2 Therefore, care of ST‐segment elevation myocardial infarction (STEMI) in the elderly could become a public health problem in the coming years.

Despite their relative importance within the spectrum of STEMI patients, elderly patients are usually poorly represented in clinical trials.3, 4 The clinical evidence on the optimal management of STEMI in the elderly is scarce. Only 3 randomized trials addressed reperfusion therapy in elderly patients with STEMI.5, 6, 7 Their mean ages were between 80 and 81 years, with small sample sizes and conflicting results. Furthermore, and possibly due to the special characteristics of these patients and their logical difficulty for inclusion in randomized studies, some of the above studies had recruitment problems. The external validity of their findings to the general elderly population could be another important limitation.

Current recommendations8 emphasize the need to individualize patient management, taking into account their clinical status and comorbidities. It also emphasizes the importance of recording conditions such as frailty and cognitive impairment, because of their relationship with in‐hospital management and clinical outcomes, and also the need to assess important clinical conditions in these patients such as functional capacity and quality of life.

Little information exists about the impact of frailty, functional status, and cognitive impairment on the outcomes of patients with MI. Frailty is an emerging concept characterized by vulnerability and functional impairment.9 There is no absolute consensus about frailty measurement. Some scales have been described during the last years. Recent data suggest a high prevalence of frailty in elderly patients with ischemic heart disease undergoing percutaneous coronary intervention (PCI)10 and in patients with non–ST‐segment elevation MI.11 Other geriatric syndromes such, as cognitive impairment and severe dependence, are also common among elderly patients hospitalized for acute heart diseases.12 Frailty9, 13, 14, 15 and geriatric syndromes11, 16 have been associated with a worse prognosis in elderly patients. Frailty has also been associated with functional impairment in elderly patients after percutaneous aortic valve replacement.17 However, the prevalence of frailty, cognitive and functional decline, and their impact on the outcomes in patients with STEMI undergoing primary PCI are unknown. A correct description of these aspects could become an important tool for improving therapeutic management in elderly patients in this clinical scenario.

Therefore, the aim of the IFFANIAM (Impact of frailty and functional status in elderly patients with ST segment elevation myocardial infarction undergoing primary angioplasty) study is to analyze the characteristics of a cohort of unselected elderly patients undergoing primary PCI for STEMI, describe their baseline functional and cognitive status and comorbidities on admission, and to assess the impact of these factors on their midterm mortality and functional outcome.

Methods

Study Design, Clinical Setting, and Population

The present study is an observational multicenter registry to be conducted at 4 tertiary care hospitals in Spain (Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Barcelona; Hospital General Universitario Gregorio Marañon, Madrid; Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, and Hospital Universitari Josep Trueta, Girona). All consecutive patients age 75 years or older undergoing primary PCI for STEMI will be prospectively included. The primary outcome will be the description of 1‐year mortality, and its causes and associated factors. Secondary outcomes will be functional capacity and quality of life (Figure 1).

Figure 1.

Impact of frailty and functional status in elderly patients with ST segment elevation myocardial infarction undergoing primary angioplasty. Abbreviations: BI, Barthel index; LI, Lawton‐Brody index; MINA‐SF, Mini Nutritional Assessment–Short Form; SAQ, Seattle Angina Questionnaire.

Therapeutic Protocol

Criteria for primary PCI will be presentation within 12 hours of onset of chest pain suggestive of acute myocardial infarction and ST‐segment elevation >0.1 mV in 2 or more adjacent leads or new‐onset (or presumed new‐onset) left bundle‐branch block.

Patients will be pretreated with an oral dose of aspirin (250–300 mg), 1 P2Y12 inhibitor and 1 intravenous anticoagulant (either unfractionated heparin or bivalirudin), and directly transferred to the catheterization lab. Access site, antithrombotic treatments during angiography, and choice of stents and other devices will be left to the operator's decision according to current recommendations.18 Afterward, patients will be admitted to the respective coronary care units.

Data Collection

Data will be recorded prospectively by trained physicians using standardized case report forms. We will record demographic data, baseline clinical characteristics, electrocardiographic, laboratory parameters, and echocardiographic and angiographic findings. Data about in‐hospital clinical course will also be collected, such as invasive procedures requirements (Swan‐Ganz catheter, intra‐aortic counterpulsation, endotracheal intubation, mechanical ventilation, renal replacement therapy) and in‐hospital complications (bleeding, location, need for transfusion, surgery or nonsurgical intervention for bleeding, infectious complications requiring antibiotic, reinfarction, mechanical and arrhythmic complications, hospital mortality). In‐hospital incidence of delirium will also be recorded.

Geriatric Assessment

Baseline assessment will be conducted during admission by performing an interview with the patient and/or family/caregivers. Functional capacity for basic activities for daily living (ADL) will be assessed by the Barthel index (BI).19, 20, 21 This is an ordinal scale with a total score of 0 to 100, where intermediate ranges help evaluate the different degrees of dependency: total (0–20), severe (21–40), moderate (41–60), mild (61–90), and independent (>90). To evaluate the ability of developing instrumental ADL, we will use the Lawton‐Brody index (LI),22 whose values range from 0 to 8 and analyzes 8 instrumental daily‐living activities. Mobility will be assessed using a scale that consists of 4 major parts: ability to walk indoors, ability to walk 400 m, ability to climb up 1 floor, and average time (in hours) that the patient walks per day.23 Mobility score values range from 0 (total independency) to 8 (complete dependency). We also will apply a short questionnaire about social support. The questions about these measures will refer to the pre‐MI status.

Cognitive status will be assessed with the Pfeiffer test.24 We will also assess frailty by using both the FRAIL scale25, 26 and Fried criteria.27 The FRAIL scale includes evaluation of fatigue, resistance, ambulation, illness, and weight loss. Fried criteria includes the 5 criteria of unintended weight loss in preceding year, exhaustion, physical activity, gait speed, and grip strength. Taking into account the context of the acute clinical setting of the study and the limitations of the measure of ambulation, we will use a modification of the Fried criteria excluding only the variable walk speed from this evaluation. The other Fried criteria will be tested. For handgrip strength evaluation we will use a digital dynamometer, with the scores recorded to the nearest 0.1 kg.28 The assessment for frailty will be performed in patients after their PCI procedure.

For the evaluation of comorbidity we will apply the Charlson index29 based on 12 long‐term conditions (with a maximum score of 37 points) and collect the number of drugs taken by the patient. Previous diagnosis of depression and specific treatment requirements will also be collected. Nutritional risk assessment will be performed using the Mini Nutritional Assessment–Short Form (MNA‐SF),30 whose values range from 0 to 14 points; scores below 11 identify patients at risk of malnutrition.

Quality of life will be analyzed by the Seattle Angina Questionnaire (SAQ),31 which was designed for patients with stable coronary artery disease, though it has also been applied in patients with acute coronary syndromes.32 It consists of 19 items that assess 5 key areas: frequency of angina episodes, stability of angina, physical limitation, treatment satisfaction, and disease perception. This questionnaire has demonstrated adequate validity, reproducibility, and relationship with prognosis. SAQ values range from 0 to 100, and higher values indicate less symptom burden and higher quality of life.

Follow‐up

Functional capacity (BI), ability for developing instrumental activities (LI), mobility score, social support, and cognitive ability (Pfeiffer) will be reassessed by telephone at 3 months. Quality of life will be evaluated with the SAQ questionnaire.

A clinical follow‐up will be performed 1 year after discharge by review of medical records, telephone contact with the patient or family, or the patient's referring physician. Overall mortality and its causes, need for hospitalization and its causes, reinfarction, and need for coronary revascularization will be collected. Deaths due to myocardial infarction, sudden death, or heart failure will be considered of cardiac origin. BI, LI, mobility score, social support, and the quality of life through the SAQ will also be reassessed.

Sample Size

Little information exists about the impact of frailty, functional status, and comorbidities on outcomes in elderly patients with STEMI, thus there is a lack of enough data to allow precise measurement of sample size. Assuming a 1‐year mortality of around 20%, a sample size of 500 patients will enable a sufficient number of events to study the primary outcome of the study.

Statistical Analysis

Categorical variables will be expressed as number and percentage. Quantitative variables will be expressed as mean and standard deviation. Those quantitative variables with non‐normal distribution will be expressed as median and interquartile range (25%–75%). The normal distribution of quantitative variables will be assessed by the Kolmogorov‐Smirnoff test. For baseline variables, Student t test will be used for comparison of quantitative variables and χ2 test or Fisher exact test, when appropriate, will be used for categorical variables (PASW Statistics 18; SPSS, Inc., Chicago, IL).

We will assess the relationship between frailty, functional status, and mortality by Cox regression method, using as an end point variable mortality at year and including each of the specified indexes as independent variables, along with the other cardiological variables showing significant association with 1‐year mortality (P < 0.05) in the univariate analysis.

Exploratory analysis of mortality will be performed using Kaplan‐Meier curves for different values of the indices of functional assessment, cognitive, nutritional, and comorbidity mentioned.

We will also develop a predictive model for 1‐year mortality using the Cox regression method, to thereby attempt to ascertain the predictive capacity that provides each of these indices to global model.

We will describe possible changes in functional ability and quality of life of patients in this clinical scenario. We also will perform exploratory analyses of baseline characteristics of patients who suffer significant functional decline or significant loss of quality‐of‐life measurements during the study period

Ethics

Inclusion in the study will not imply any changes in patients' clinical management. All patients will give written informed consent before their inclusion in this prospective study. The confidential information of the patients will be protected according to national normative guidelines. The design of this study has been revised and approved by the clinical research ethics committee of Bellvitge University Hospital (IRB00005523).

Discussion

The increase in life expectancy has resulted in a large segment of the population in industrialized countries being over 75 years of age. The incidence of MI is particularly high in the elderly. Therefore, the number of elderly patients who are hospitalized for MI will likely increase.

Comorbidities and frailty are common in this clinical setting and are associated with higher rates of complications and consumption of healthcare resources. In addition, the negative effect of hospitalization on functional outcomes is well established.33, 34 Recent data suggest a high prevalence of frailty and other geriatric syndromes in elderly patients hospitalized for different cardiac conditions. Both frailty and other geriatric syndromes have been associated with a worse prognosis in elderly patients.

The clinical evidence on the optimal management of STEMI in the elderly is scarce. Elderly patients included in clinical trials possibly do not adequately represent the general elderly population treated in daily clinical practice. Current recommendations emphasize the need to individualize patient management, taking into account their clinical status and comorbidities. It also emphasizes the importance of recording conditions such as frailty, cognitive impairment, functional capacity, and quality of life. However, little information exists about the impact of these conditions on the outcomes of patients with MI and the possible role of a comprehensive geriatric assessment in the clinical management of elderly patients with STEMI undergoing primary angioplasty. Accurate knowledge of these aspects could become an important tool for improving therapeutic management in elderly patients in this clinical scenario.

Therefore, the results of the IFFANIAM study will help to better understand the impact of conditions such as frailty, comorbidities, and functional status on outcomes in elderly STEMI patients undergoing primary angioplasty, thus potentially contributing to identifying patients at higher risk for cardiac complications and to establishing the role of a comprehensive geriatric assessment in this clinical setting. The expected increase in myocardial infarction in the elderly during the coming years calls on healthcare systems and policymakers to focus on promoting methods to improve the clinical management of this population.