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Cardiac Imaging in the Geriatric Population: What Do We Think We Know, and What Do We Need to Learn? Nidhi Mehta, Neel P. Chokshi, James N. Kirkpatrick⁎ Echocardiography Laboratory, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

A R T I C LE I N FO

AB S T R A C T

Keywords:

Cardiac imaging plays an important role in coronary artery disease (CAD), congestive heart

Imaging

failure (HF) and valvular heart disease (VHD) in the elderly. Imaging defines the structure

Elderly

and function of the cardiac system, refining the understanding of patients' anatomy and

Cardiovascular disease

physiology and informing a host of clinical care decisions, including prognosis. Yet there is a paucity of evidence to guide the rational use of many imaging modalities in patients of advanced age, a population with considerable clinical heterogeneity, high prevalence and burden of cardiovascular disease (CVD) and atypical presentations of CVD. This paper discusses important considerations for cardiac imaging for older adults, particularly in regard to CAD, VHD and HF, and then presents domains for future research to produce data that would inform clinical care guidelines, appropriate use criteria and imaging lab protocols to address the unique needs of the fast-growing elderly population. © 2014 Elsevier Inc. All rights reserved.

It has been estimated that by 2050, the number of individuals ≥ 80 years of age living in the United States (US) will increase to approximately 25 million.1 Cardiovascular (CV) disease (CVD) morbidity and mortality rates rapidly escalate as adults age into their senior years; adults aged ≥75 years account for only 6% of the US population but they account for over 60% of myocardial infarction (MI)-related morbidity and mortality events.2 Similarly, clinical burdens related to chronic coronary artery disease (CAD), congestive heart failure (HF) and valvular heart disease (VHD) are all disproportionately represented in today's burgeoning elderly population. Cardiac imaging plays an important role in all of these disease states. Imaging defines the structure and function of the cardiac system, refining the understanding of patients' anatomy and physiology and informing a host of clinical care decisions. Imaging is used for screening (detecting asymptomatic cardiac disease), diagnosing the cause of symptoms, defining the extent of cardiac

disorder in a patient with known disease (including risk stratification), monitoring the progression (or regression) of disease, and guiding therapeutic management, including decisions about aggressive therapy. Imaging has long been used to guide surgical procedures, and there has been a recent increase in the use of cardiac imaging to guide catheter based procedures.3 Yet, while all of these uses of cardiac imaging have a special relevance in the elderly, there is a paucity of evidence to guide the rational use of many imaging modalities in patients of advanced age. This paper discusses important considerations for cardiac imaging for older adults, particularly in regard to CAD, VHD and HF. Current clinical applications and areas of proposed research are described. For the purposes of this paper, cardiac imaging modalities include those which employ echocardiography, radioisotope tracers (e.g. single-photon emission computerized tomography [SPECT], radionuclide techniques), computed tomography (CT) and cardiac magnetic resonance

The authors report no disclosures. ⁎ Address reprint request to James N. Kirkpatrick, MD, Interim Associate Director, Echocardiography Lab, Physician Co-Chair, Ethics Committee, Hospital of the University of Pennsylvania, 3400 Spruce St. 9021 Gates Pavilion, Philadelphia, PA 19104. E-mail address: [email protected] (J.N. Kirkpatrick). http://dx.doi.org/10.1016/j.pcad.2014.07.003 0033-0620/© 2014 Elsevier Inc. All rights reserved.

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Abbreviations and Acronyms ACS = acute coronary syndrome AS = aortic stenosis AUC = appropriate use criteria AV = atrioventricular CAD = coronary artery disease CIED = cardiac implanted electronic device CMR = cardiac magnetic resonance CT = computed tomography CVD = cardiovascular disease ECG = electrocardiogram EF = ejection fraction eGFR = estimated glomerular filtration rate

(CMR). There are various definitions of the term ‘old age’ but we tried to focus on individuals aged 75 years and older. However, since there are no standardized stratifications of old age in the current literature, some of the studies that are described still refer to patients aged ≥65 years of age. The discussion of specific mechanisms, benefits and limitations of individual imaging modalities is beyond the scope of this document and will be briefly discussed only where appropriate.

HF = heart failure HFpEF = heart failure with preserved ejection fraction HFrEF = heart failure with reduced ejection fraction

Clinical heterogeneity of the older population

In addition to agerelated CVD, there are ICD = implantable cardioverter senescent effects in defibrillator cardiac morphology and physiology as well as LV = left ventricle broader organ sysMETS = metabolic equivalents tems changes in elderly patients. Age-related MI = myocardial infarction cardiac changes that MR = mitral regurgitation occur commonly in the elderly include MV = mitral valve reduced arterial comPET = positron emission pliance and left ventomography tricular (LV) diastolic dysfunction, physioloSPECT = single-photon emission gical states that comcomputerized tomography pound the implications TAVR = transcatheter aortic of cardiac pathologies valve replacement such as CAD, VHD and secondary cardiomyTEE = transesophageal opathies. The overall echocardiography state of aging also TTE = transthoracic adds to this underlyechocardiography ing complexity of CV VHD = valvular heart disease burden. The elderly are, for example, at an VT = ventricular tachycardia increased risk for agerelated clinical burdens that add to CV management challenges, including multimorbidity, polypharmacy, and geriatric syndromes (e.g., cognition changes, falls, delirium). HRR = heart rate recovery

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“Frailty” is a geriatric syndrome that has been used to describe a state of declining reserves in strength and function that occurs in the elderly population. Using the definition, at least 9.5% of the population between 75 and 79 years, 16% between 80 and 84 years, and 25% ≥ 85 years are frail.4 Frailty constitutes a syndrome which conveys an increased susceptibility to stressors and accounts for some of the differences between chronological and biological age in terms of disability. Frailty not only can affect CVD outcomes, it can also put individuals at increased risk for complications during diagnosis or treatment. The decision-making process regarding procedures and therapies becomes all the more complex in the frail elderly as risks and burdens more easily outweigh potential benefits, compared to younger patients. Results from cardiac imaging illuminate many of these decisions, but choices concerning whether and when to image and with what modality are greatly impacted by frailty and disability of older adults.5 The elderly subgroup is known to be at higher risk for development and progression of CVD, but none of the current trials have an adequately sized elderly group to be examined in isolation. More than half of all trials of CAD in the past decade did not enroll any patient ≥ 75 years of age. The elderly subgroup accounted for only 9% of all patients enrolled in trials.2 Only three large community registries contributed data describing community elders with acute coronary syndrome (ACS), which included the National Registry of Myocardial Infarction (NRMI), Global Registry of Acute Coronary Events (GRACE), and Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE). Evidence supporting the value of cardiac imaging in the elderly population is even more difficult to ascertain. The ambiguous value of cardiac imaging in the elderly raises significant questions regarding the appropriate use of resources in this population.

Appropriate imaging Any discussion of imaging indications in the elderly must start with the Appropriate Use Criteria (AUC). The AUC were developed by the American College of Cardiology and other specialty societies in response to concerns over growing resource utilization in CV medicine. It has long been recognized that substantial societal resources are expended on cardiac diagnostic and therapeutic procedures and that there are substantial geographical variations in resource utilization.6,7 With the goal of improving quality in cardiac resource utilization, the AUC seeks to guide the rational use of procedures, with the goal of defining and reducing the inappropriate use of these procedures. The AUC related to cardiac imaging were among the first AUC produced in the mid-2000s and were based on appropriate use criteria produced by the radiology community. Several of the AUC have undergone revisions, and more are planned. Currently, there are AUC addressing transthoracic (TTE), transesophageal (TEE) and stress echocardiography,8 cardiac computed tomography,9 and cardiac radionuclide imaging.10 Also, there are more recent documents addressing the use of stress testing in stable CAD11 and imaging in HF.12

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It is acknowledged that all of these AUC will be used to guide clinical care but also reimbursement decisions by payers. As CV providers anticipate more restricted reimbursements, subspecialty societies are becoming more attentive to the metrics by which appropriateness of diagnostic procedures are determined. As defined by the AUC Task Force in relation to imaging, “An appropriate imaging study is one in which the expected incremental information, combined with clinical judgment, exceeds the expected negative consequence by a sufficiently wide margin for a specific indication that the procedure is generally considered acceptable care and a reasonable approach for the indication.”.13 Of note, negative consequences include not only the potential direct toxicity of a test or intervention (e.g. radiation from CT), but also the adverse downstream effects of an inaccurate test result (e.g. exposure to the risks of invasive angiography after a false positive stress test). A detailed description of the methodology for developing AUC for imaging is beyond the scope of this document. Briefly, ratings panels convened to consider the appropriateness of indications for each area of focus (e.g. stress testing, echocardiography) assigned ratings that placed specific indications into one of three categories.12 Appropriate Care is defined as “benefits generally outweighing risks…procedure is generally acceptable and is generally reasonable for the indication.” May be Appropriate Care (previously called “Uncertain”) generally includes indications for which there is a paucity of evidence but there are other factors (risk benefit, experience of the clinician, population variability) which indicate the procedure may be appropriate. Rarely Appropriate Care (formerly known as “Inappropriate”) describes procedures which have a “lack of a clear benefit/risk advantage” for the indication, and therefore the “procedure is not generally acceptable and is not generally reasonable for the indication.” Importantly, the decision to re-label the “inappropriate” category came about in part to acknowledge that there are clinical scenarios where even these “rarely appropriate” indications may yield clinical benefit, but substantial justification needs to be provided. In general, the AUC Task Force addressed the use of cardiac imaging in specific clinical scenarios which fall under the indications listed in Table 1. In each of these clinical scenarios, the overriding assumption is that an appropriate imaging test is one that has the potential to change management, either in terms of changing some aspect of clinical care, or of providing reassurance that no such change is necessary. Thus, asymptomatic and stable patients with cardiac disease may still be appropriate candidates for imaging if their cardiac conditions involve residual anatomical or physiological abnormalities which, if found to be worsening, would prompt a therapeutic intervention or change. Cardiac imaging can be appropriate in asymptomatic patients without known disease who have elevated risk for developing disease, and in whom the early detection of disease would lead to changes in clinical care.12 Both asymptomatic and symptomatic patients, imaging findings which aid prognostication can provide clinically important information, even if they do not lead to specific interventions. Importantly, imaging studies ordered “out of curiosity” do not

Table 1 – Categories of indications in the appropriate use criteria. Initial diagnosis Guidance of clinical management Evaluation of changes in clinical status or cardiac exam findings Early follow-up (defined either as within 1 or 2 years) without changes in clinical status or cardiac exam Late follow-up (>1 or >2 years) without change in clinical status or cardiac exam Adapted from Hendel et al.13

fall under this rubric, nor do most “routine” studies when there is little or no suspicion for a change in findings. Given the ambiguity of symptoms and high prevalence of CVD and/or concomitant comorbidity in the elderly, there is an understandable tendency to order imaging assessments relatively more frequently. Very little evidence exists, however, as to the proper interval of testing, but the AUC generally regard early follow imaging in asymptomatic patients to be unnecessary. The AUC do not integrate age as a factor in determining the appropriateness of an imaging test, in part due to a lack of data. Nonetheless, there are a number of other important factors associated with aging which impact the use of cardiac imaging in the senior population.

Important considerations for cardiac imaging in the elderly High risk, high prevalence, high burden A key aspect of advanced age, is that the concept of high risk burden must be considered in the context of age-related management efficacy. In contrast to younger populations, the high risk, high prevalence and high burden of disease in the elderly population leads to a situation in which cardiac imaging is likely to detect disease for which the implications of therapy is uncertain. Thus, if structural or functional abnormalities are detected in an asymptomatic patient, management decisions may still remain ambiguous. Detection of non-obstructive atherosclerotic CAD in an elderly diabetic with peripheral vascular disease will, for example, not likely lead to any intensification of medical therapy beyond that which is already indicated (e.g. moderate to high intensity statin and aspirin at a minimum, and beta blocker and ACE inhibitor in many clinical scenarios).14 The detection of asymptomatic, severe, multivessel CAD in a patient with end stage, metastatic lung cancer who is not a chemotherapy candidate is unlikely to impact the overall prognosis or therapeutic decision-making. In contrast, in other scenarios imaging has substantial clinical impact, including rationale for selecting patients mostly likely to benefit from interventions that may prolong and improve quality of life. For example, an ejection fraction (EF) < 30% in a HF patient provides an indication for an implantable cardioverter defibrillators (ICD) and helps to establish candidacy for a biventricular pacemaker. Similarly, quantifying the degree and character of aortic stenosis guides

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decisions about valve replacement. Furthermore, serial imaging to detect progression may identify worsening disease before it is clinically apparent, another key perspective for management choices. Patients with valvular lesions which progress to severe regurgitation, for example, benefit from surgical interventions before the developoment of ventriculopathy.15,16

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With changes of normal aging a high prevalence of disease and disability, the elderly may be at higher risk for complications during imaging and may be less able to participate to allow optimal test performance. Common considerations for the choice of optimal imaging studies are discussed below, taking into account comorbidities, test risks, frailty and disability, and cognitive dysfunction, addressing metabolic derangements, radiation and logistics (Fig 1).

Prognosis and decision-making about life prolonging interventions Decreased renal function Imaging facilitates both critical diagnostic and prognostic perspectives. While assigning a poor prognosis is often employed to justify an intervention, in older popultions a poor prognosis uncovered by imaging may also justify non-intervention. Multivalve involvement with biventricular dysfunction in a patient with severe peripheral vascular disease may, for example, direct goals of care away from the OR and in the direction of comfort measures. Similarly, detection of severe LV dysfunction in an elderly patient with a cancer responsive only to cardiotoxic chemotherapy may help direct management towards hospice care. The best intervention for an elderly patient found to have cardiac amyloidosis is also likely to be palliative care consultation.

Atypical presentation Atypical symptoms occur more often in the elderly than in younger patients, leading to delays in diagnosis and treatment that may be reduced with judicious using of cardiac imaging. Atypical symptoms have been shown to have a 3-fold higher risk of in-hospital death [13% versus 4%, P < 0.001], in part because of the under-utilization of evidence-based therapies. 2 Whereas silent or unrecognized infarctions accounted for 25% of all MIs, they accounted for up to 60% of MIs in patients ≥ 85 years of age.2 In the Global Registry of Acute Coronary Events for non-ST elevation MI, the average age of patients presenting with atypical symptoms was 73 years, whereas the average age of patients presenting with typical symptoms was 66 years.17 While a high clinical index of suspicion is the most important element in caring for the elderly, imaging is a crucial next step to detect or confirm pathology. Although chest pain remains a common presentation of ACS regardless of age, elderly patients were more likely to present with dyspnea (49%), diaphoresis (26%), nausea and vomiting (24%) and syncope (19%) as the primary complaint. 18 Imaging in the setting of such nonspecific symptoms helps to narrow the differential diagnosis, as well as direct interventions. For instance, the rapid identification of a reduced LVEF, an obstructive coronary lesion, severe valvular regurgitation, or a new regional wall motion abnormality allows the rapid initiation of therapies to address cardiac causes of dyspnea.

Practical considerations Most imaging studies involve some degree of risk and/or discomfort or require patient positioning and cooperation.

Older adults tend to have decreased renal function from normal aging as well as intrinsic pathology. Patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 are at significant risk for nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis from the use of gadolinium for cardiac CMR.19 Contrast nephropathy during cardiac CT scanning is a significant concern in patients with creatinine clearance < 60 mL/min/1.73 m2.20 In addition, most elderly patients are at increased risk due to age-related renal changes. 21 Further, optimal imaging in CT ideally requires a regular heart rhythm and low heart rates for appropriate gating. To achieve slow heart rates, imaging protocols often call for pushes of intravenous beta blockers during the study which may be more complicated in the elderly who are susceptible to conduction disease, hypotension, falls, and other possible effects of the medication.

Electrophysiological disease Significant resting ECG abnormalities are also common in the elderly and limit the utility of non-imaging exercise stress testing. Both baseline ST changes and left bundle branch block complicate interpretation of exercise-only stress testing.22 The use of dipyridamole, adenosine and regadeneson is complicated in patients with high degree atrioventricular (AV) block. As elderly patients have a high prevalence of conduction disease, clinical history and ECG should be reviewed to exclude high grade AV block as well as risks from bronchospasm (see below) prior to testing. Regadeneson may be tolerated better than other vasodilators among older adults due to improved side effect profile and shorter duration of action though the potential for side effects still remains an important concern.23 Dobutamine is an effective pharmacological stress agent but can be arrhythmogenic, inducing both supraventricular arrhythmias and ventricular tachycardia (VT). Studies in elderly patients, however, suggest that using dobutamine as well as atropine for diagnostic testing is generally well-tolerated. The administration of dobutamine and atropine for stress testing was investigated in a study of 179 patients over 70 years of age. Side effects that caused premature end of the test were severe chest pain in 5 patients (2.8%), ECG changes in 1 patient (0.6%), hypotension in 2 patients (1.1%), and cardiac arrhythmia in 2 patients (1.1%).24 Similarly, a study by O'Driscoll et al.25 showed that dobutamine infused during stress echo was well tolerated in 550 patients, with only 12 (2.2%) patients experiencing dobutamine-induced atrial fibrillation and one patient (0.2%) experiencing non-sustained VT.

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Risk of Complications (Heart block, Nephrotoxicity) Clinical Utility

Risk Reduction (procedural guidance)

(Disease Detection, Prognostication)

Practical Imaging Considerations Cognitive dysfunction (Informed consent, Compliance with test)

Frailty and Disability (Patient positioning) Comorbidities (Renal dysfunction, CIEDs)

Fig 1 – Practice Imaging Considerations in the Geriatric Population.

Electrophysiologic-related issues are also relevant in respect to the fact that older adults often have implanted hardware. Cardiac implantable electronic devices (CIEDS—pacemakers and ICDs) are common in older patients, and often complicate the use of CMR in this group. Implanted metallic objects such as pacemakers and ICDs can be affected by the magnetic field generated to produce CMR images. In addition to causing the leads to move, CMR causes programming changes in the device itself. Newer, MRI-safe devices and newer CMR protocols are beginning to circumvent some of these problems, but such protocols are not in wide use, and the problem of imaging artifact from CIEDs remains.26

Pulmonary disease Chronic obstructive pulmonary disease is common among older populations, and elderly patients with pulmonary disease may not be able to tolerate certain forms of stress tests. Patients with lung disease may be unable to exercise to the point of adequate cardiac stress due to dyspnea. Bronchospastic conditions may be exacerbated by vasodilator stress agents (dipyridamole, adenosine). Newer agents (such as regedenoson) may help lower vulnerability to these side effects.27

Radiation There is a widely-recognized association between cumulative radiation and life-time risk of cancer, but the practical applicability of the risk of low dose medical radiation in elderly patients is controversial.28,29 Most radiation-induced cancers have long latency periods, and the elderly are likely to die of some other disease (especially cardiac disease) before developing this type of cancer. For many geriatric patients, the risks of non-detection or non-characterization of cardiac disease therefore outweigh the risks of radiation-induced cancer.30 On the other hand, for elderly patients who have already received large amount of diagnostic and/or therapeutic radiation earlier in life, additional radiation from CT scans and radionuclide tests may present at least a theoretical concern as cumulative effects accrue, especially in younger subgroups of elderly (e.g. 65–75) who still might have decades of anticipated lifespan. Therefore, imaging modalities that avoid radiation stand out as particularly appealing in relation to these safety concerns. Echocardiography and CMR provide information on cardiac structure and function in older populations, and can be used effectively with exercise, dobutamine (echo) and vasodilator (CMR) stress tests.

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Age-related logistic considerations Most cardiac imaging modalities (with the exception of echocardiography which can be performed on a patient in a wheelchair, though optimal images are acquired with the patient in the left lateral decubitus position) require a patient to get on to an imaging table. With increasing age and prevalence of frailty, patients will require more assistance from the staff performing the study and may not be able to comply with study requirements. For example, elderly patients may have limited ability to perform exercise stress testing and achieve an adequate level of stress. The most basic type of stress test entails an exercise modality, with assessment of ischemia by ECG. Since many elderly patients are deconditioned and or have mobility, balance, gait speed, and/or other limitations, exercise testing is often challenging. Kallinen et al.31 found that 60% of patients >75 years of age (n = 282) could not perform an exercise test or had to stop the test prematurely. While bicycle stress testing may address some of these problems in some older adults, it has not been well studied, particularly in American populations. SPECT testing requires patients to lie flat and without any movement for 20–40 minutes with arms extended at rest and again during stress imaging. For a frail patient or an elderly patient with significant musculoskeletal disease, this can be an extremely challenging task both for the patient and those administering the study. Any patient movement during the study will create artifacts and reduction in the quality of the study potentially leading to falsely positive or non-diagnostic studies. Though not universally available, a positron emission tomography (PET)/CT perfusion study may be more practical due to the shorter imaging time (a study can be completed within 30 minutes). CMR testing is also limited by logistic requirements; patients must lie flat for up to 60 minutes within a small enclosure. This requirement, as well as the associated vulnerability to anxiety and/or an inability to tolerate pretesting sedation may exclude patients from this test. While echocardiography can be performed with patients in wheelchairs or in other positions, optimal images are only acquired when the patient lies in the left lateral decubitus position for 30–45 minutes. Some echo views are optimized with breath holds. Even with optimal positioning and breathing cooperation, echocardiographic images are more likely to be non-diagnostic in older adults due to age-related increases in chest wall deformities and pulmonary disorders.

Cognitive dysfunction Dementia and more subtle changes in executive cognition are common in the elderly and may impair the ability of some patients to understand their disease process and to comply satisfactorily to the testing requirements. Cognitive limitations may, for example, diminish the reliability of informed consent discussions prior to cardiac imaging tests, and/or compromise patients' ability to fulfill the instructions required for good testing quality. Patients may lack decisional capacity to provide true informed consent regarding a specific test. This loss of situational or specific decisional capacity for a

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given test may co-exist with retained decision-making capacity regarding other aspects of care. For example, an elderly patient with dementia may be unable to comprehend the renal risks of CT coronary angiography but be able to comprehend the potential discomfort involved with an echocardiogram. While psychiatric and ethics consultants can assist with determination of capacity, any clinician may make a determination of lack of capacity. In these situations, a surrogate decision-maker should provide the informed consent, considering what the patient would have wanted if he or she could make an informed decision, and the best interests of the patient. Legal statutes governing surrogates vary from state to state. A determination by a medical provider of lack of decision-making capacity must be differentiated from declaring a patient legally incompetent, which can only be done by a court. Legal incompetence is a global, as opposed to situational, declaration that a patient is sufficiently mentally impaired as to be incapable of making rational decisions, particularly those concerning healthcare options. Such patients require surrogate decision-makers (often court-appointed guardians) to make all medical decisions. CMR and CT studies require patients to follow very specific instructions during the study, such as breath holding, which could be difficult in those with impaired cognition or hearing loss. Echocardiography and SPECT imaging generally have fewer requirements, though patients must cooperate with specific tasks involving transfers and lying still for these procedures. As a practical matter, ordering physicians discuss or convey any special needs related to functional and cognitive disability with the lab performing the test at the time of ordering the test.

Imaging in specific cardiac disease states Coronary artery disease Stress testing is useful for both the diagnosis of CAD as well as in determining long term prognosis. Given the high pretest probability of CAD in relation to advanced age, the prognostic utility of a stress study may be particularly useful. A number of trials have demonstrated effective prognostic assessments using exercise stress testing, stress echocardiography, and SPECT perfusion imaging in the elderly. Both imaging and non-imaging stress test parameters are useful for prognosis. A study of exercise ECG in patients with a mean age of 81 years demonstrated particular value of heart rate recovery (HRR) of ≤18 beats/minute decrease in the minute after exercise to predict all-cause mortality, additive to ischemic ST changes (hazard ratio: 2.86; 95% CI: 1.01–8.11).32 Another study highlighted the importance of exercise capacity in older populations. Chokshi et al, (currently in submission) showed the ability to exercise on a treadmill is independently predictive of all-cause mortality in adults aged 80 years and older. Only 9% of patients were able to complete the exercise protocol, but those who did demonstrated improved survival (HR 0.52, 0.33 – 0.81, p = 0.003, median survival of 9.5 vs. 5.9 years). Moreover, the capacity to achieve higher METS (metabolic equivalents) was associated with a better prognosis (HR 0.83 per MET, 0.70 – 0.99). A number of studies have demonstrated that imaging with pharmacological or exercise stress provides additional

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prognostic power. In particular, the number of ischemic wall segments on stress echocardiography predicts cardiac morbidity and mortality. A study by Chokshi et al. (unpublished data) showed all-cause mortality correlated directly with the number of ischemic segments (HR 1.49, 1.05–2.13). Three separate studies of dobutamine stress echocardiography in patients >80 years of age also demonstrated that extent of ischemia was also associated with mortality and CVD events.21,24 Stress myocardial perfusion imaging with the use of SPECT has also been validated in the elderly. In particular, moderate and severe defects on SPECT imaging provided accurate prognostication in octogenarians.33 Zafrir et al.34 compared octogenarians and patients < 80 years who were undergoing stress myocardial perfusion imaging. The elderly group had a lower prevalence of CAD risk factors but high degrees of ischemic events and cardiac mortality. SPECT imaging predicted adverse outcomes in both groups. One study considered the optimal stress testing modality in the elderly. In a meta-analysis of 13,304 patients >65 years of age, Rai et al.35 compared non-invasive modalities to determine the optimal imaging choice for cardiac risk stratification. The population was obtained from seventeen studies with a median age of 75.5 years. This paper demonstrated that stress myocardial perfusion imaging (OR: 11.8, 95% CI 7.5–18.7) and stress echocardiography (OR: 3.2, 95% CI: 2.6–3.9) accurately predicted cardiac death or non-fatal MI. However, exercise treadmill with ECG alone did not (OR: 3.1, 95% CI: 0.8-11.5). The limitations of this study included the lack of prospective design and the fact that exercise provocation could be done in ways that were better tailored to the capacities of older adults (such as bicycle stress testing). In summary, the available evidence suggests that stress testing for prognosis in the elderly should ideally be accomplished with exercise. Imaging adds additional prognostic power and is necessary as part of pharmacological stress, for the majority of the elderly who cannot complete a treadmill exercise protocol (though they may be able to perform bicycle exercise).

Valvular disease imaging in the elderly Compared to those addressing CAD, there are far fewer studies of VHD imaging in the elderly, though with the growing focus on transcatheter aortic valve replacement (TAVR) the particular value of imaging for common valvular decisions in older adults has advanced as a clinical priority. The valvular lesions with the most evidence in the elderly are aortic stenosis (AS) and mitral regurgitation (MR).

Aortic stenosis Results from the Cardiovascular Health Study show that in patients aged 65–75 years, 75–85 years, and older than 85 years severe AS is present in 1.3%, 2.4%, and 4%, respectively.36 The Euro Heart Survey reported that 56% of the patients with AS were >70 years of age and 36% had one or more comorbidity.3 Echocardiography is the central imaging modality to detect and characterize the degree of AS. Candidacy for surgical aortic valve replacement and for TAVR are based on

echocardiographic gradients and valve area. Patient with reduced LV systolic function may have gradients which do not meet TAVR criteria (mean gradient ≥ 40 mmHg) but may still have severe AS. In these cases, re-measurement with Doppler echo during dobutamine administration to augment LVEF may increase mean gradient to the requisite range. Other patients' valves will open more widely with increased left ventricular output, demonstrating “pseudostenosis”. Patients with LVs which do not augment with dobutamine may have a worse prognosis but may still benefit from aortic valve replacement.37 Echocardiography also provides important information on concomitant VHD, right ventricular size and function and pulmonary pressures. In addition to TTE contrast-enhanced CT imaging in necessary to ensure that vasculature will be able to tolerate the large bore catheters that are required for the procedure. Moreover, in the process of evaluating the vasculature, extracardiac findings are often detected, particularly in the elderly. In a retrospective study by Gufler et al.,38 significant extravascular incidental findings were detected in 23.5% of 131 patients >70 years of age (mean age 82 years). In the thorax, significant incidental findings were detected in 14.5% patients, including 2 (1.5%) lesions being classified as potentially malignant. In the abdomen, significant incidental findings were identified in 9.2% of patients, with three (2.3%) being considered potentially malignant. The value of such surveillance is particularly important given the high susceptibility of older adults to pathologies that impact the overall value of TAVR. There is a relatively high chance of detecting incidental findings that affect prognosis to the extent that patients may no longer be candidates for TAVR, and/or that require additional interventions to reduce morbidity and mortality.

Mitral regurgitation About 9% of patients >75 years of age have moderate-severe MR. However, up to 85% of octogenarians with symptomatic or severe MR are denied mitral valve (MV) repair or replacement surgery, and thus there are limited data on outcomes in this population.39,40 In the most comprehensive study of MV surgery in the elderly to date, investigators reviewed 322 octogenarians at two hospitals with significant MV surgical experience. Compared to MV repair, MV replacement resulted in significantly higher 30 day mortality (18.9% vs. 11.0%, adjusted OR 3.4, p = 0.028), and gastrointestinal complications (14.7% vs. 4.0%, adjusted OR 6.2, p = 0.004).41 In a similar study, Nloga and colleagues42 found replacement resulted in significantly higher 30 day mortality (18.5% vs. 2.5%, p = 0.004); MV replacement was also the only predictive factor of operative mortality in multivariate analysis (OR 6.7, p = 0.04). Thus, assessment of repairability of the MV is a key management and prognostic parameter. Usually, these assessments rely on TTE and TEE. Particularly with the use of newer 3D modalities, TEE provides precise detail of MV anatomy and function and can be used for surgical planning.3,43 Newer percutaneous MV repair techniques are also options for some elderly patients who are poor surgical candidates. A description of the procedure can be found elsewhere.44 As in determination of the surgical repairability of the MV, TEE is necessary to demonstrate leaflet anatomy amenable to novel percutaneous interventions.

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Heart failure imaging in elderly Approximately 1%–2% of the adult population in developed countries has HF, with the prevalence rising to ≥10% among persons 70 years of age or older. Annual incidence rates of HF in the US per 1000 population range from 8.2 for white women age 65 to 74 years of age to 65.2 for white men ≥85 years of age.45 Heart failure is underdiagnosed in elderly patients who often lack specific symptoms and usually present with comorbidities that can confound diagnostic assessments based primarily on symptoms. Therefore, echocardiography plays an important complementary role in establishing a diagnosis for patients with HF symptoms. Echocardiography assesses cardiac morphology and physiology and helps differentiate between different causes of HF symptoms, as well as differentiating cardiac from pulmonary etiologies of dyspnea, thereby guiding management priorities. In a cross-sectional study, 585 participants with mean age of 74.1 years, over half of patients (n = 366) had abnormal ECG or NT-pro-BNP > 125 pg/mL. These patients subsequently underwent echocardiography. A minority (15.7%) had heart failure from three different etiologies: 17 had HF with reduced EF or HFrEF (65 years of age. Am J Cardiol. 2012;110:1092-1099. 36. Deutsch MA, Bleiziffer S, Elhmidi Y, et al. Beyond adding years to life: health-related quality-of-life and functional outcomes in patients with severe aortic valve stenosis at high surgical risk undergoing transcatheter aortic valve replacement. Curr Cardiol Rev. 2013;9:281-294. 37. Ozkan A, Hachamovitch R, Kapadia SR, Tuzcu EM, Marwick TH. Impact of aortic valve replacement on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction. Circulation. 2013;128(6):622-631. 38. Gufler H, Schulze CG, Wagner S. Incidental findings in computed tomographic angiography for planning percutaneous aortic valve replacement: advanced age, increased cancer prevalence? Acta Radiol. 2014;55:420-426. 39. Bonow RO, Carabello BA, Chatterjee K, et al. Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/AmericanHeart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008;118:e523-e661.

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40. Mirabel M, Iung B, Baron G, et al. What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? Eur Heart J. 2007;28:1358-1365. 41. Chikwe J, Goldstone AB, Passage J, et al. A propensity scoreadjusted retrospective comparison of early and mid-term results of mitral valve repair versus replacement in octogenarians. Eur Heart J. 2011;32:618-626. 42. Nloga J, He´naine R, Vergnat M, et al. Mitral valve surgery in octogenarians: should we fight for repair? A survival and qualityof-life assessment. Eur J Cardiothorac Surg. 2011;39:875-880. 43. Kadakia MB, Kirkpatrick JN, Silvestry FE. Echocardiography in percutaneous mitral valve interventions. Curr Cardiovasc Imaging Rep. 2012;5(6):452-461. 44. Philip F, Athappan G, Tuzcu EM, Svensson LG, Kapadia SR. MitraClip for severe symptomatic mitral regurgitation in patients at high surgical risk: a comprehensive systematic review. Catheter Cardiovasc Interv. 2014 Jun 6. http://dx.doi. org/10.1002/ccd.25564. [Epub ahead of print]. 45. Go AS, Mozaffarian D, Roger VL, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6-e245. 46. van Riet EE, Hoes AW, Limburg A, Landman MA, van der Hoeven H, Rutten FH. Prevalence of unrecognized heart failure in older persons with shortness of breath on exertion. Eur J Heart Fail. 2014;16(7):772-777. 47. Rigolli M, Whalley GA. Heart failure with preserved ejection fraction. J Geriatr Cardiol. 2013;10(4):369-376. 48. Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011;32(6):670-679.

49. Mureddu GF, Agabiti N, Rizzello V, et al. Prevalence of preclinical and clinical heart failure in the elderly. A population-based study in Central Italy. Eur J Heart Fail. 2012;14:718-729. 50. Komajda M, Lam CS. Heart failure with preserved ejection fraction: a clinical dilemma. Eur Heart J. 2014;35 (16):1022-1032. 51. Wan SH, Vogel MW, Chen HH. Pre-clinical diastolic dysfunction. J Am Coll Cardiol. 2014;63(5):407-416. 52. Khan FZ, Virdee MS, Palmer CR, et al. Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial. J Am Coll Cardiol. 2012;59(17):1509-1518. 53. Adelstein E, Alam MB, Schwartzman D, et al. Effect of echocardiography-guided left ventricular lead placement for cardiac resynchronization therapy on mortality and risk of defibrillator therapy for ventricular arrhythmias in heart failure patients (from the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region [STARTER] trial). Am J Cardiol. 2014;113(9):1518-1522. 54. Bilchick KC, Dimaano V, Wu KC, et al. Cardiac magnetic resonance assessment of dyssynchrony and myocardial scar predicts function class improvement following cardiac resynchronization therapy. J Am Coll Cardiol Img. 2008;1:561-568. 55. Feldman D, Pamboukian SV, Teuteberg JJ, et al. The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: executive summary. J Heart Lung Transplant. 2013;32(2):157-187. 56. Kirkpatrick JN, Wiegers SE, Lang RM. Left ventricular assist devices and other devices for end-stage heart failure: utility of echocardiography. Curr Cardiol Rep. 2010;12(3):257-264.

Cardiac imaging in the geriatric population: what do we think we know, and what do we need to learn?

Cardiac imaging plays an important role in coronary artery disease (CAD), congestive heart failure (HF) and valvular heart disease (VHD) in the elderl...
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