Listen to this manuscript’s

audio summary by

JACC Editor-in-Chief

Dr. Valentin Fuster.

J O U R N A L O F T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y VO L . 7 1 , N O . 1 8 , 2 0 1 8

ª 2 0 1 8 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N

P U B L I S H E D B Y E L S E V I E R

JACC FOCUS SEMINAR: CVD IN THE ELDERLY

JACC STATE-OF-THE-ART REVIEW

Valvular Heart Disease inPatients $80 Years of Age

Susheel K. Kodali, MD,a Poonam Velagapudi, MD, MS,a Rebecca T. Hahn, MD,a Dawn Abbott, MD,b

Martin B. Leon, MDa

ABSTRACT

ISS

Fro

Pro

sci

Mi

rec

no

dir

dis

Ma

In the United States, the octogenarian population is projected to triple by 2050. With this aging population, the prev-

alence of valvular heart disease (VHD) is on the rise. The etiology, approach to treatment, and expected outcomes of VHD

are different in the elderly compared with younger patients. Both stenotic and regurgitant lesions are associated with

unfavorable outcomes if left untreated. Surgical mortality remains high due to multiple co-morbidities, and long-term

survival benefit is dependent on many variables including valvular pathology. Quality of life is an important consideration

in treatment decisions in this age group. Increasingly, octogenarian patients are receiving transcatheter therapies, with

transcatheter aortic valve replacement having the greatest momentum. Numerous transcatheter devices for management

of other valve lesions are currently in early clinical trials. This review will describe the epidemiology, etiology,

diagnosis, and therapeutic options for VHD in the oldest old, with a focus on transcatheter technologies.

(J Am Coll Cardiol 2018;71:2058–72) © 2018 by the American College of Cardiology Foundation.

L ife expectancy in the United States is on therise, with the population >80 years of age pro-jected to triple from 11.4 million in 2010 to

32.4 million in 2050 (1). The prevalence of valvularheart disease (VHD) increases with age, with degener-ative valve disease thought to be the most commonVHD in the elderly (2–4). Population studies haveshown mitral regurgitation (MR) and aortic stenosis(AS) are the most prevalent valvular disorders in theelderly. Medical therapies for degenerative VHD areprimarily for symptom control, with valve replace-ment therapy being the treatment of choice (5). How-ever, surgical valve repair or replacement may beassociated with significant morbidity and mortalityin the elderly due to comorbidities, complex

N 0735-1097/$36.00

m the aColumbia University Medical Center/New York Presbyterian Hos

vidence, Rhode Island. Dr. Kodali has served as a consultant for and re

ences, and Abbott Vascular; served on the advisory board and received eq

crointerventional Devices, and Biotrace Medical; and has served on the

eived no compensation. Dr. Hahn has served on the Core Lab for multiple

direct compensation. Dr. Leon has served as a member of the PARTNER

ect compensation. All other authors have reported that they have no rel

close.

nuscript received January 3, 2018; revised manuscript received March 9,

structural anatomy (i.e., atherosclerosis in the aortaor mitral annular calcification [MAC]), frailty, andimpaired cerebral perfusion (6,7). Studies in octoge-narians have reported short-term mortality rates ofvalve surgery of approximately 8% to 20%, withhigher mortalities for mitral valve (MV), multiplevalve, and concomitant coronary artery bypass graft-ing operations (8,9). The balance between the initialrisks and eventual benefits of surgery is reduced inthe elderly (10). Goals of treatment in this patientgroup may differ from those of younger patients,with quality of life, functionality, maintaining inde-pendence, and palliation of severe symptoms takingprecedence over increased longevity (11) (CentralIllustration).

https://doi.org/10.1016/j.jacc.2018.03.459

pital, New York, New York; and bBrown University,

ceived honoraria from Claret Medical, Merrill Life-

uity from Thubrikar Aortic Valve, Inc., Dura Biotech,

PARTNER trial steering committee, for which he

aortic intervention trials for which she has received

Trial Executive Committee, for which he receives no

ationships relevant to the contents of this paper to

2018, accepted March 22, 2018.

AB BR E V I A T I O N S

AND ACRONYM S

AR = aortic regurgitation

AS = aortic stenosis

BAV = balloon aortic

valvuloplasty

MAC = mitral annular

calcification

MR = mitral regurgitation

MS = mitral stenosis

MV = mitral valve

SAVR = surgical aortic valve

replacement

TAVR = transcatheter aortic

valve replacement

TR = tricuspid regurgitation

J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8 Kodali et al.M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2 Valvular Heart Disease in the Elderly

2059

Recently, transcatheter valve technology hasevolved as a suitable alternative to surgery for thetreatment of VHD in elderly patients. It has demon-strated improved survival in high-risk elderly pa-tients, despite the morbidity from an invasiveprocedure, with a 20% reduction in absolute mortal-ity at 1 year compared with medical therapy (12). Asthere is paucity of data in this age group, decisionsabout treatment need to be individualized based onspecific valve pathology, comorbid conditions, andpatient preferences. In this review we discuss theetiology, epidemiology, diagnosis, and managementof common valvular pathologies encountered in theoctogenarian population, with a focus on trans-catheter technologies.

EPIDEMIOLOGY AND ETIOLOGY

The prevalence and etiology of VHD in the elderly isdetermined by population-based studies (Table 1).The U.S. study of Nkomo et al. (2) included 11,911subjects who prospectively underwent echocardio-graphic examination in 3 large national population-based epidemiological studies: the CARDIA(Coronary Artery Risk Development in Young Adults)(13), ARIC (Atherosclerosis Risk In Communities) (14),and CHS (Cardiovascular Health Study) (15) studies.The age-adjusted prevalence of moderate or severeVHD was 2.5% (95% confidence interval [CI]: 2.2% to2.7%), and was significantly influenced by age: <2.0%prevalence in those <65 years of age and 13.2% inthose $75 years of age. Increasing age (per 10 years)was significantly associated with MR (1.84; 95% CI:1.70 to 1.99; p < 0.0001), mitral stenosis (MS) (1.65;95% CI: 1.12 to 2.43; p ¼ 0.01), aortic regurgitation(AR) (1.49; 95% CI: 1.30 to 1.70; p < 0.0001), and AS(2.51; 95% CI: 2.02 to 3.12; p < 0.0001). After adjustingfor age, there were no sex differences in VHD preva-lence, except for AS (odds ratio: 1.52; 95% CI: 1.02 to2.26; p ¼ 0.04). In subjects $75 years of age, the mostfrequent VHD was MR (9.3%; 95% CI: 8.1% to 10.9%),followed by AS (2.8%; 95% CI: 2.1% to 3.7%), AR(2.0%; 95% CI: 1.4% to 2.7%) and MS (0.2%; 95% CI:0.1% to 0.6%).

The etiology of VHD has been ascribed to “degen-erative” disease; however, the precise cause of thisdegeneration may be difficult to define. Although notperformed in an appropriate population for epide-miological study, the Euro Heart Survey (3) prospec-tively performed echocardiograms on 5,001 patientsreferred to a hospital during a 4-month period in2001, in 92 centers across 25 European countries. Inthis selective population of patients, AS was the most

frequent disease, followed by MR, AR, andMS. Degenerative disease was thought to bethe most common etiology (63%), followed byrheumatic disease (22%), and other etiologies(15%) such as endocarditis and inflammatoryor congenital disease. Although no pharma-cologic therapies have been shown to preventprogression, the pathophysiology of VHD iscomplex and is often characterized by an in-flammatory process; in the future, therapiestargeted at the root cause of the degenerativeprocess may provide a therapeutic alternativethat can be utilized early in the disease state(16).

Another U.S. study demonstrated a 9% to10% prevalence of MR in the elderly, butfailed to distinguish primary (or degenera-

tive) from secondary (or functional) etiologies of MR(2). The Framingham study similarly showed an 11.1%prevalence of $moderate MR in men (with none inwomen) 70 to 83 years of age and did not distinguishprevalence by valve morphology (4). In this study,MR was associated with a history of congestive heartfailure and myocardial infarction. Other studies havesuggested that secondary MR occurs in approximately25% of patients following myocardial infarction andin up to 50% of those with heart failure with reducedejection fraction (17–20). It is thus more likely that, inthe setting of increasing prevalence of ischemic heartdisease with age, the prevalence of secondary MRexceeds that of primary MV disease in the elderly.Irrespective of the etiology, severe MR is associatedwith progressive left ventricular dilatation anddysfunction (5). Prognosis and treatment, however,are distinctly different based on the etiology of theMR (5,20–22), and thus accurate diagnosis of valvemorphology is an important first step in determiningappropriate treatment options in the elderly (5).

The 2% to 3% prevalence of significant calcific AS inthe elderly seen in the study by Nkomo et al. (2) hasbeen confirmed in other smaller population-basedstudies with differences attributable to varying defi-nitions of AS (23–25). In the Lindroos et al. (23) study,critical AS, defined as a valve area #0.8 cm2 or ve-locity ratio of #0.35, had a prevalence of 2.9% (95%CI: 1.4% to 5.1%) in the 75- to 86-year-old group. Inthe Stewart et al. (24) study, AS was defined asincreased leaflet thickness and Doppler velocitiesof $2.5 m/s; the prevalence was 2.4% in 75 to 84 yearsof age and 4% in those $85 years of age. The Tromsøstudy (25) performed in Norway defined any AS as amean gradient of $15 mm Hg (severe stenosis as amean gradient $50 mm Hg); the prevalence of any

CENTRAL ILLUSTRATION Successful Management of Valvular Heart Disease in the Elderly

Kodali, S.K. et al. J Am Coll Cardiol. 2018;71(18):2058–72.

Successful management of valvular heart disease in the elderly involves shared decision making between the patient, patient’s family, and heart team. Multiple factors

must be taken into consideration, and the importance of each factor will vary among the different parties involved. CAD ¼ coronary artery disease;

TVT ¼ transcatheter valve therapy.

Kodali et al. J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8

Valvular Heart Disease in the Elderly M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2

2060

stenosis was 9.8% in the 80 to 89 years of age cohort;however, patients who underwent aortic valvereplacement surgery (presumably those with severeAS) comprised only w2% of the population. Congen-ital bicuspid valve disease is the second most com-mon reason for AS (26), with patients typicallypresenting with degenerative aortic disease atyounger ages (fifth to seventh decades) and alsoassociated aortopathy. Nonetheless, in a recent se-ries, 22% percent of octogenarians presenting forsurgery for isolated AS had bicuspid valve disease(27). A systematic review and meta-analysis including9,723 patients >75 years of age reported that theprevalence of AS was 12.4%, while severe AS was3.4%. Furthermore, 40% of those patients wereconsidered high surgical risk. Based on this, it isprojected there may be approximately 290,000transcatheter aortic valve replacement (TAVR) can-didates, with 27,000 becoming newly eligible annu-ally (28).

The 2% prevalence of significant native AR in theelderly (2) is also confirmed in the Framingham HeartStudy (4) where $moderate AR was 2.2% in men and2.3% in women 70 to 83 years of age. Another smaller

population study demonstrated a higher incidence,with moderate-to-severe AR in 13% of patients over 75years of age (23). Given the anatomy of the aorticvalve, AR may result from disease of either the aorticleaflets or the aortic root because any distortion of theleaflets preventing their correct apposition may leadto leaflet malcoaptation. Primary leaflet abnormal-ities, such as endocarditis or rheumatic disease, mayoccur in the elderly; however, the more commonetiology of AR in the elderly is aortic root dilatation orfibrocalcific disease of the valve or root leading toleaflet malcoaptation. In the HyperGEN (Genetics ofLV Hypertrophy) study, AR was directly related toage, aortic valve fibrocalcification, and female sex,and negatively related to body mass index (p < 0.005)(29). Hypertension was once thought to result inaortic root dilatation and thus AR, but multiplestudies have failed to show a significant relationshipbetween blood pressure and AR (4,29). Other lesscommon causes include primary aortic disease or abicuspid aortic valve (30). The association of bicuspidaortic valve with dilatation of the ascending aorta hasbeen well-established (31) and not only maycontribute to the occurrence of valve regurgitation,

TABLE 1 Etiology of Valvular Heart Disease in the Elderly

Valvular Lesion Causes

Mitral regurgitation Primary/degenerative (less common):Mitral valve prolapse

Rheumatic fever

Infective endocarditis

Secondary/functional (more common):Myocardial infarction

Heart failure with reducedejection fraction

Atrial fibrillation

Aortic stenosis Senile calcific degeneration (most common)Bicuspid aortic valve

Aortic regurgitation Degenerative (fibrocalcific disease of theaortic valve)

Dilatation of the aortic rootBicuspid aortic valveRheumaticInfective endocarditis

Mitral stenosis Degenerative/mitral annular calcificationMainly rheumaticMalignant carcinoid

Tricuspid regurgitation Primary (less common):Congenital

Rheumatic

Neoplastic

Trauma

Infective endocarditis

Endomyocardial fibrosis

Iatrogenic pacer lead implantation

Right ventricular biopsy

Secondary causes (more common):Left heart disease

Pulmonary hypertension

Right ventricular infarction

Chronic right ventricular pacing

Atrial fibrillation

J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8 Kodali et al.M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2 Valvular Heart Disease in the Elderly

2061

but also may result in aortic complications that in-fluence prognosis (32).

Globally, the most common etiology of MS isrheumatic heart disease (33). However, MAC is animportant cause of calcific MS, especially in theelderly. The exact incidence of MAC causing degen-erative MS remains unclear, but is estimated to occurin 2.5 to 18% of elderly patients (34,35). Its incidencewas 10% in patients >50 years of age and 33% in those>90 years of age in 1 series (36). The Euro HeartSurvey reported that degenerative MS accounted for12.5% of MS cases (3). The diagnosis of degenerativeMS due to MAC is made by the typical appearance ofmarked calcification with reduced leaflet excursionby computed tomography or echocardiography,increased gradient by Doppler, and reduced valvearea by continuity equation or 3-dimensionalplanimetry (37). Posterior annular calcification is

more common in MAC, with 1 series demonstratingisolated posterior annulus calcification in 33%, ante-rior and posterior annuli affected in 11%, and isolatedanterior calcification in 5% (38). In this same series,the severity of calcification was also more dramaticon the posterior annulus. This has significant impli-cations for surgical treatment options, as adequatedebridement of the posterior annulus to allow forsuturing of MV prosthesis can be challenging. Thiscan result in post-operative paravalvular regurgita-tion due to suture dehiscence or, in the worst-casescenario, catastrophic posterior disruption of the leftventricle.

Tricuspid regurgitation (TR) is the second mostcommon VHD after MR and its prevalence also in-creases with age (4). It is estimated that about 1.6million individuals in the United States are known tohave moderate to severe TR, with an estimated inci-dence of 1.2% to 1.5% in the general population (39).Recent observations demonstrated that TR was morecommon in the elderly and in women (4,40). Datafrom the Framingham Heart Study demonstrated that1.5% of men between 70 and 83 years of age and 5.6%of women between 70 of 83 years of age were noted tohave at least a moderate amount of TR (4). Functionalor secondary TR due to left heart disease is the mostcommon etiology of TR in the elderly and isfrequently associated with other VHD, especially MR,in >30% of cases (41,42). Other common causesinclude pulmonary hypertension, right ventricular(RV) infarction, chronic RV pacing, and history ofatrial fibrillation (AF) (5). Primary causes of TR ac-count for 25% of cases and are due to congenital,rheumatic, neoplastic, traumatic, infective endo-carditis, endomyocardial fibrosis, or iatrogenic pacerlead implantation or RV biopsy (43). Regurgitationdue to structural heart disease is associated withprogressive right atrial and RV remodeling resultingin dilatation of the tricuspid annulus or papillarymuscles (44), while TR in the absence of underlyingstructural heart disease is called idiopathic TR andcommonly attributed to elderly age and AF (45).Annular dilatation in functional TR occurs along theanterior and posterior tricuspid valve leaflet attach-ments, causing the annulus to become more circularand planar with a greater degree of TR associatedwith larger atrial and ventricular volumes andremodeling (46). There are significant differences inthe mechanism of TR due to idiopathic or secondarycauses. With idiopathic TR, there is marked basal RVdilatation with relatively normal RV length, as well asmarked annular dilatation but with normal tentingheight. With functional TR associated with pulmo-nary hypertension, there is significant lengthening of

TABLE 2 Reasons for Increased Mortality and Morbidity of

Surgery for Valvular Heart Disease in the Elderly

1. Comorbidities Atrial fibrillationDiabetes mellitusChronic kidney diseaseCerebrovascular disease

2. Frailty

3. Complex structural anatomy Atherosclerosis in the aortaMitral annular calcification

4. Impaired cerebral perfusion

Kodali et al. J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8

Valvular Heart Disease in the Elderly M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2

2062

the RV with less basal dilatation consistent withelliptical or spherical RV deformation, as well as someannular dilation (less than idiopathic patients) andsignificantly greater tenting height than idiopathicpatients (45). These mechanistic differences havesignificant implications for both surgical and (poten-tially) transcatheter treatment options. Severity of TRis associated with worse 1-year survival and unfa-vorable outcomes independent of age and other co-morbid conditions (47).

MANAGEMENT OF VHD

Management of VHD in the elderly requires a multi-disciplinary approach involving cardiologists, inter-ventional cardiologists, surgeons, anesthetists,mid-level providers. Shared decision making be-tween the medical team and the patient is particu-larly important because quality-of-life improvementis an important consideration in the elderly. Decisionaids, designed to increase patient knowledge andengagement in shared decision making, increase pa-tient satisfaction and reduce decisional conflict (48).

Historically, surgery has been the mainstay oftreatment for VHD in all age groups, including octo-genarians. Current indications for surgery are gener-ally based on the presence of symptoms (49).However, this often presents a problem in the elderlyas symptoms are often minimized and attributed to“getting older.” In addition, the contribution of co-morbidities, such as chronic obstructive pulmonarydisease, to symptoms often confounds the picture.Although the American College of Cardiology (ACC)/American Heart Association (AHA) VHD guidelinessupport the use of stress testing to elicit symptoms,this is challenging in an elderly population that oftenhas limited mobility. Nevertheless, studies haveshown that even in octogenarians and nonagenarians,surgical treatment improves survival and returns it toage appropriate norms (50).

Short-term mortality rates of valve surgery in oc-togenarians have been reported from 8% to 20%, withhigher mortality for MV, multiple valve, andconcomitant coronary artery bypass grafting

operations (8,9). Several studies have demonstratedhigher surgical aortic valve replacement (SAVR)morbidity and mortality, ranging from 5 to 18%, inoctogenarians when compared with younger patients(51–54). However, physicians often tend to over-estimate surgical risk in octogenarians; there is recentdata suggesting excellent short- and long-term out-comes in this population following SAVR (55,56). Inreality, age is often not the most significant factor indetermining surgical risk. Based on the Society ofThoracic Surgeons (STS) surgical risk calculator, the30-day predicted risk of mortality with SAVR in anaverage size healthy man only increases from 1.0% to1.6% as age increases from 70 to 80 years. Neverthe-less, age is often an important psychological factor inassessing risk and often “advanced age” is the reasonprovided for not referring a patient for surgery (57).Rather than age, it is often the comorbid conditionsthat also increase with age that result in higher sur-gical morbidity and mortality (Table 2).

Comorbidities such as diabetes mellitus, chronickidney disease, cerebrovascular disease, and AFdecrease the functional reserve required for post-operative recovery and lead to worse outcomes. Inone series of elderly patients, diabetes was reportedin 34% of those undergoing valve replacement forsevere AS (58). Prior studies have demonstrated thatdiabetic patients are at increased risk for sternalwound infections, postoperative respiratory failure,postoperative renal failure, need for blood trans-fusions, and in-hospital mortality when comparedwith nondiabetics (59,60). Presumably, this is due tomultisystem inflammation and dysfunction in di-abetics, along with associated conditions such asrenal dysfunction. Acute kidney injury has been re-ported to occur in up to 30% of patients after cardiacsurgery, with up to 3% of patients requiring dialysis,with higher incidence in elderly patients (61). Bothacute and chronic renal insufficiency are predictors ofoperative mortality and poor long-term survival,especially in cardiac surgery of the elderly (62,63).Atrial fibrillation is a common cardiac dysrhythmiaassociated with VHD, and has an estimated preva-lence of 20% to 40% (64). The prevalence of post-operative atrial fibrillation remains high in elderlypatients undergoing valve replacement (65) and isassociated with increased risk of morbidity and mor-tality (66).

One comorbidity that requires special attention inthe octogenarian is frailty, defined as a syndrome ofimpaired physiologic response and decreased resis-tance to stressors (67). Quantitating frailty in anobjective manner poses a significant challenge. Friedet al. (68) developed a system to assess frailty in the

FIGURE 1 Degenerative Mitral Valve Disease Secondary to Severe Mitral Annular Calcification

(A) Echocardiographic, (B) fluoroscopic, and (C, D) computed tomography images from a patient with degenerative mitral valve disease secondary to severe mitral

annular calcification. (E) Echocardiographic, (F) fluoroscopic, and (G, H) computed tomography appearance after successful transvenous transseptal transcatheter

mitral valve replacement utilizing the SAPIEN 3 prosthesis (Edwards Lifesciences, Irvine, California).

J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8 Kodali et al.M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2 Valvular Heart Disease in the Elderly

2063

general population by quantifying impairment in thecore domains of wasting and malnutrition, weakness,slowness, and inactivity. Various studies haveadapted these measures to evaluate their impact onoutcomes after cardiac surgery. One surgical seriesdemonstrated that frailty, defined by slow gait speed,was predictive of mortality or major morbidity aftercardiac surgery independent of the STS risk score.Other studies have since confirmed that frailty,defined by various metrics, is predictive of poor out-comes after cardiac surgery (69–71). The phenotype offrailty increases with aging, and a recent study inhigh-risk patients undergoing surgery (mean 83.2years of age) demonstrated that more than 75% ofpatients had at least 1 measure of frailty, most oftenslow gait speed (72).

The surgical treatment of MV disease in the elderlyoften poses more challenges in terms of clinical de-cision making than aortic valve disease. Althoughthere are no clear numbers, as noted previously,secondary MR likely plays a bigger role in octoge-narians than in younger patients. Whereas theguidelines clearly support surgical treatment for pri-mary MR, the guidelines for secondary MR, in theabsence of concomitant coronary artery bypassgrafting requirement, are less certain and recommend

surgical intervention only in patients with refractorysymptoms after optimization of medical therapy andcardiac resynchronization therapy (49). Therefore, inmany elderly patients, deciding whether to intervenein severe symptomatic functional MR is challenging,as clinical benefit is uncertain.

The appropriateness of repair versus replacementdepends on both the etiology of MR and patientcharacteristics. The high recurrence rate of regur-gitation after valve repair for secondary MR, andthe lack of evidence that surgery prolongs life,especially with advanced age, have brought intoquestion the utility of surgical repair for isolatedsecondary MR (73). In studies of ischemic MR,although 30-day mortality was higher with replace-ment, there was no difference in 1-year mortality orleft ventricular volume changes between repair andreplacement. In addition, the patients in the repairgroup had more heart failure related adverseevents, including rehospitalizations. Therefore,especially in the elderly, replacement is likely thepreferred strategy, especially in the presence ofadditional echocardiographic features such as basalleft ventricular aneurysms, severe left ventriculardilatation, or tethered leaflets, where repair can betechnically challenging.

Kodali et al. J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8

Valvular Heart Disease in the Elderly M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2

2064

The bulk of evidence supporting MV repair in oc-togenarians is for primary MR (74,75). A recent studyfrom the National Health Service central registry(n ¼ 341, mean $75 years of age) reported superiorlong-term survival after MV-repair versus replace-ment at 1, 2, and 5 years (93.4%, 91.6%, 76.9% vs.77.2%, 75.2%, 58.7%; p ¼ 0.03) (74). Another study in322 patients with mean 82.6 � 2.2 years of agecomparing MV repair versus replacement (75)demonstrated higher 90-day mortality with MVreplacement versus repair (31.6% vs. 18.9%; p ¼ 0.01).The adjusted 1-, 3-, and 5-year survival for patientsundergoing mitral repair was significantly higher at 71� 3%, 61 � 4%, and 59 � 4%, compared with 56 � 5%,50 � 6%, and 45 � 6% for patients undergoing MVreplacement (p ¼ 0.046). Multivariate analysisdemonstrated that MV replacement was highly pre-dictive of early mortality and reduced survival.

A recent meta-analysis with 24 studies including5,572 octogenarian patients (76) reported an overallhigh operative mortality of 15% with MV surgery. Thishigh mortality rate is expected in elderly patientswith multiple comorbid conditions where surgery isperformed mainly to relieve symptoms. Based on theavailable data, MV repair is the surgical treatment ofchoice for primary degenerative MR, as this preservesthe functional components of the valve including thechordal-ventricular attachments. However, the risk-benefit matrix of a complex repair versus a replace-ment changes as the patient ages. In the end, relief ofregurgitation with the lowest risk possible is the pri-mary goal. If MV replacement is to be performed, abioprosthetic valve is the choice in elderly patients toavoid the need for anticoagulation (49). Given thelimited survival of octogenarians, tissue valve dura-bility is likely adequate for this elderly population.

MV surgery can be technically challenging in thepresence of severe MAC that is commonly seen in theelderly (6). Extensive decalcification during surgerycan lead to nonrepairable atrioventricular discon-nection or delayed rupture of the left ventricle whilepartial decalcification can lead to paraprosthetic leaksdue to poor adaptation of the prosthesis ring to therugged annulus. Due to these anatomic concerns,several operators have used a transcatheter SAPIEN 3valve (Edwards Lifesciences, Irvine, California),implanted via either open surgical or percutaneoustransvenous transseptal approach, to allow forplacement of a prosthesis without removing themitral annular calcium (Figure 1). The feasibility andsuccess of this approach is being investigated inmultiple registries. The availability of transcathetertechnologies has allowed surgeons to utilize these

devices to treat complex surgical disease utilizinginnovative hybrid approaches to potentially reducesurgical risk.

MV replacement for MS in elderly patients has amuch higher mortality and worse outcome than inyounger patients. Several observational studies inelderly patients undergoing MV replacementdemonstrated a high short-term mortality of 25% to30% (77–79) and 54% mortality at 5 years (77,79). Mostof the deaths that occurred at 30 days were likely dueto severe congestive heart failure possibly due toalteration in the left ventricular dimensions andgeometry seen post MV replacement.

TR often poses the most challenging treatmentdilemma as it is sometimes difficult to ascertain theetiology and symptom status. Often, the main symp-tom is fatigue, which can be multifactorial in thiselderly population. Also, severe TR is tolerated formany years and the natural history of disease pro-gression is not well understood. Unfortunately, forthis reason, patients, most often elderly, are managedconservatively until they present with severe rightheart failure and ascites. At this point, it is too late tooffer any therapy due to extreme risk and poor like-lihood of functional recovery. Currently, there are noClass I indications for isolated tricuspid valve surgeryin the ACC/AHA guidelines. Although severe TR mayimprove after treatment of a left-sided valve lesionand reduction of RV afterload, this is unpredictable.Because adding tricuspid valve repair during left-sided surgery does not add appreciably to the risksof surgery, it is currently recommended to repair TRin patients undergoing left-sided valve surgery (49).Recent guidelines recommend (Class IIa indication)isolated tricuspid valve surgery for patients withsymptoms due to severe primary TR, includingcongestive hepatopathy, preferentially before onsetof significant RV dysfunction (49). However, the riskof operation is high in these patients; a recent studydemonstrated a mortality rate of 7.9% at 30 days, withage being an independent predictor on multivariableanalysis (80).

Though surgery is the mainstay of treatment, theelevated operative mortality associated with surgeryin the elderly must be balanced against its potentialbenefits. Goals of treatment in this patient group maydiffer from those of younger patients, with quality oflife and maintaining independence taking precedenceover increased longevity. Recently, transcathetervalve technology has evolved and gained popularityas a suitable alternative for the treatment of VHD inelderly patients given its minimally invasive natureand faster discharge post-procedure.

FIGURE 2 Commercially Available Transcatheter Heart Valves for Treatment of Aortic Stenosis

(A) Balloon-expandable Edwards SAPIEN S3 transcatheter heart valve (THV) (Edwards Lifesciences, Irvine, California), (B) self-expanding

CoreValve System Evolut R (Medtronic, Dublin, Ireland), and (C) Evolut Pro THV (Medtronic).

J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8 Kodali et al.M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2 Valvular Heart Disease in the Elderly

2065

TRANSCATHETER THERAPIES

AORTIC VALVE DISEASE. TAVR has emerged as aneffective and less invasive solution in the manage-ment of patients with severe AS, with excellent earlyand midterm clinical outcomes (81–84). TAVR hasseveral advantages over SAVR, including shorterhospital stay and faster recovery, which is particu-larly relevant to the oldest old who experience frailty,poor functional capacity, and malnutrition. Twotypes of transcatheter aortic valves are currentlyapproved by the U.S. Food and Drug Administrationfor the treatment of symptomatic severe AS inextreme, high-, and intermediate-risk patients(Figure 2). The first is the balloon-expandable SAPIEN

series, with the SAPIEN 3 transcatheter heart valvebeing the latest iteration, and second is the self-expanding CoreValve System (Medtronic, Dublin,Ireland), with the newer-generation Evolut R andEvolut Pro transcatheter heart valves. Initial studiesin extreme (12,83) and high-risk surgical candidates(72,81) leading to the approval of the first-generationdevices were conducted in an elderly population(mean w83 years of age) with multiple comorbidities.These studies demonstrated that even in an elderlypopulation, TAVR provided a survival benefit overmedical therapy and was noninferior to SAVR. In fact,the CoreValve high-risk trial demonstrated superior-ity over SAVR in terms of mortality and stroke at 2years (85). Based on these data, TAVR was a given a

Kodali et al. J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8

Valvular Heart Disease in the Elderly M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2

2066

Class I recommendation for treatment of high-riskpatients with AS in the most recent update of ACC/AHA VHD guidelines.

Subsequent trials in lower-risk patients with theballoon-expandable SAPIEN XT valve (84) and theCoreValve (58) demonstrated that TAVR was non-inferior to SAVR in intermediate-risk surgical can-didates. Although these patients were lower-risksurgical candidates than in the original trials, themean age of the population was only 1 to 2 yearsyounger. In both studies, TAVR was associated withlower rates of adverse events such as acute kidneyinjury, bleeding requiring transfusion, and newonset AF. These important complications have beenshown to result in worse outcomes, especially inelderly patients. This benefit with TAVR is likelywhy the transfemoral subgroup of the PARTNER IIA(Placement of Aortic Transcatheter Valves) studywith the SAPIEN XT valve experienced significantlylower 2-year rates of mortality and disabling strokewith TAVR compared with SAVR. This benefit wasfurther amplified in the PARTNER II S3i study inintermediate-risk patients utilizing the SAPIEN 3valve. Utilizing a propensity score analysis, thisstudy demonstrated a dramatic benefit with lowerrates of death and stroke at 1 year with TAVR overSAVR, once again in an elderly population (86).

The large number of patients enrolled in thesetrials has allowed development of risk prediction al-gorithms for patients undergoing TAVR. A recentanalysis including 3,687 patients demonstrated thathome oxygen use, assisted living, albumin levels <3.3g/dl, and >85 years of age predicted death at 30 dayswhile home oxygen use, albumin levels <3.3 g/dl,falls in the past 6 months, STS Predicted Risk ofMortality score >7%, and severe ($5) Charlson Co-morbidity Index score predicted death at 1 year (87).In addition, post-operative delirium was also found tobe associated with increased morbidity and mortalityfollowing TAVR (88). This draws attention to anoften-unrecognized constellation of risk factorsparticularly prevalent in hospitalized elderly pa-tients, including delirium, falls, disability, and lack offamily or social support, that has significant relevancefor patients undergoing TAVR.

Many of the previous patient characteristics areconsistent with the “frailty phenotype” describedpreviously. Although frailty has been associated withworse outcomes following cardiac surgery, a recentstudy examined the impact of frailty status on TAVRoutcomes and demonstrated that despite longer post-procedural hospital stay (9 � 6 days vs. 6 � 5 days;p ¼ 0.004), there was no significant differencein acute procedural success or periprocedural

complications. However, frailty was associated with ahigher 1-year mortality (11).

One of the earliest studies to directly evaluateoutcomes of TAVR in the elderly was an analysis ofnonagenarians from the PARTNER-I trial, whichincluded 531 patients (329 transfemoral and 202transapical TAVR access procedures) with a mean ageof 93.0 � 2.1 years (89). The 30-day mortality withtransfemoral and transapical TAVR was 4.0% and12.0%, respectively, while 30-day stroke was 3.6%and 2.0%, respectively. These event rates were notdissimilar to those in younger patients. In addition,health status, measured with the Kansas City Car-diomyopathy Questionnaire, showed significantimprovement from baseline in this elderly cohort.Since then, there have been several manuscriptspublished on the safety and feasibility of TAVR inoctogenarian and nonagenarian patients with signif-icant comorbid conditions (90–92).

The largest U.S. experience with nonagenarianscomes from the STS/ACC TVT (Transcatheter ValveTherapeutics) registry including 3,773 patients >90years of age (92). The results showed that afteraccounting for a higher STS Predicted Risk of Mortalityin nonagenarians as compared with the youngercohort (10.9% vs. 8.1%; p < 0.001), the observed-to-expected mortality ratios at 30 days were similar($90 years of age vs. <90 years of age: 0.81 [95% CI:0.70 to 0.92] vs. 0.72 [95% CI: 0.67 to 0.78]). The 12-item Kansas City Cardiomyopathy Questionnairescore at 30 days was slightly lower in nonagenarians ascompared with the younger patients (70.8 vs. 72.9;p ¼ 0.006), but was similar at 1 year (79.2 vs. 81.3;p ¼ 0.539). Yamamoto et al. (90) reported on thelargest non-U.S. experience in treating octogenariansand nonagenarians with severe AS in the FRANCE-2(FRench Aortic National CoreValve and Edwards)registry. The study included 2,254 patients $80 yearsof age who underwent TAVR with either a self-expanding (n ¼ 710) or balloon-expandable valve(n ¼ 1,544). There was no significant difference acrossage groups in 30-day mortality (80 to 84 years of age,10.3% vs. 85 to 89 years of age, 9.5% vs. $90 years ofage, 11.2%; p ¼ 0.53) or 1-year mortality (19.8% vs.26.1% vs. 27.7%; p ¼ 0.16). These studies confirmedthe safety and effectiveness of TAVR in both octoge-narians and nonagenarians. Another common indica-tion for TAVR in the elderly is failure of a previouslyimplanted surgical bioprosthesis. Several studies havedemonstrated the feasibility of this approach withreasonable risk, but there are limited long-term dataregarding durability of the TAVR (93,94).

As discussed previously, the current guidelinesrecommend triaging patients to either TAVR or SAVR

FIGURE 3 Creation of Double Orifice Valve to Treat Mitral Regurgitation

(A) Schematic drawing of a surgical bow-tie mitral valve repair (Alfieri stitch) to treat mitral regurgitation with creation of a double orifice mitral valve. (B) Schematic

drawing demonstrating creation of a double-orifice mitral valve via a transcatheter approach utilizing the Mitraclip device (Abbott Vascular) (reproduced with

permission from Maisano et al. [111]).

J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8 Kodali et al.M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2 Valvular Heart Disease in the Elderly

2067

based on elevated surgical risk as assessed by a heartteam. Currently, trials in low-risk patients areongoing. One concern about treating lower-risk pa-tients is lack of long-term durability data with TAVR.However, core lab echocardiographic data out to 5years demonstrates no significant concern at present(95). In an elderly population, where survival may belimited, durability may be less of a concern. Althoughthe guidelines do not reference age as a criterion inchoosing TAVR over SAVR, the reality is that ageplays a role in the heart team decision, especiallygiven the excellent results with TAVR in recentstudies. A special mention needs to be made aboutolder adults with severe AS who are not candidatesfor intervention, either TAVR or SAVR, due to theircomorbidities. With the availability of a less invasivetherapy such as TAVR, it often becomes difficult toidentify those patients that are “too sick” for treat-ment. The key question to answer is whether thepatient is dying “with AS” or “from AS”? Clearly,there are patients whose prognosis will not changedespite relieving AS, such as those with stage 4 lungcancer or severe debilitation from multiple comor-bidities. In these patients, the goal should remainpalliation of symptoms. Kapadia et al. (82) showedimprovement in functional status and survival in theshort term with balloon aortic valvuloplasty (BAV) ininoperable patients with severe AS when comparedwith no BAV. Thus, in this population, BAV may beconsidered a temporizing measure for symptomimprovement, but it should be used thoughtfully.

In the patient with end-stage cancer with refractoryheart failure symptoms, it is reasonable to considerBAV to improve quality of life. However, in theseverely frail patient who is bed bound due to mul-tiple comorbidities, it is unlikely to change quality oflife or survival. As with the decision for TAVR orSAVR, it should be made by a multidisciplinary heartteam and should engage both the patient and care-givers in the process with a clear elucidation of risksas well as potential benefits.MV DISEASE. Although surgery remains the goldstandard for MV disease, especially degenerative MR,elderly patients are often not referred for therapy dueto high surgical risk (96). Transcatheter therapieshave the potential to provide a lower-risk therapy,but many challenges remain. Much of the challenge istechnical because the etiology of MV disease is com-plex and the anatomic limitations of the currentlyavailable therapies are significant. Nevertheless,there is great interest in developing these technolo-gies, as surgical options for MV disease in elderlypatients are fraught with risk. Several technologiesare at different stages of investigation to minimizethe surgical trauma and related risks with reasonableearly, short-term success, but long-term data arelimited.

In the United States, the MitraClip (AbbottVascular, Santa Clara, California) is currently the onlyapproved device for transcatheter treatment of MR. Itis indicated in patients with degenerative MR at highor prohibitive risk of surgery (97). It is performed via a

Kodali et al. J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8

Valvular Heart Disease in the Elderly M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2

2068

transvenous transseptal approach, mimics the surgi-cal Alfieri stitch (Figure 3), an edge-to-edge repairperformed under transesophageal echocardiogramguidance.

Currently, there is limited experience with Mitra-Clip in octogenarians. Most studies to date have beenon septuagenarians at high surgical risk, but resultscan be extrapolated. The randomized EVEREST II(Endovascular Valve Edge-to-Edge Repair Study) thatcompared the transcatheter treatment with surgery in279 patients (30% $75 years of age) demonstratedsuperior safety with major adverse events occurringin 15% of patients in the percutaneous-repair groupand 48% of patients in the surgery group at 30 days(p < 0.001), but MitraClip was less efficacious inpreventing secondary MR (98). Data from the GRASP(Getting Reduction of Mitral Insufficiency by Percu-taneous Clip Implantation) registry including 180patients with 1-year follow-up showed the primaryefficacy endpoint (composite of death, surgery for MVdysfunction, and grade 3þ or 4þ MR) of device ther-apy in high-surgical-risk patients with moderate-to-severe or severe MR was similar between <75 yearsof age and $75 years of age (23.9% vs. 25.2%;p ¼ 0.912). Similar all-cause mortality was also seen(10.8% vs. 13.3% p ¼ 0.574) (99). Another study (100)comparing outcomes of 136 patients$80 years of ageundergoing either conventional surgery (MV repair orreplacement) or transcatheter procedure demon-strated no significant differences in either proceduralsuccess (100.0% vs. 96.0%) or 30-day mortality (7.1%vs. 4.8%) between the groups. However, residualpostoperative MR $2 at discharge was greater in thetranscatheter group (0.0% vs. 23.8%). At 1 year, 4(9.52%) patients died in the surgical group versus 9(21.40%) patients in the transcatheter group. In aretrospective study of 60 patients age $80 years ofage with isolated degenerative MR who underwentisolated transcatheter (n ¼ 25) or surgical (n ¼ 35, 29repairs and 6 replacements) mitral intervention, thetranscatheter group was associated with significantlyfewer complications (p < 0.05), but more residual MR>2þ (p < 0.01). Two-year actuarial survival rate waslower for transcatheter approach (90% vs. 97%; p <

0.01) (101).As stated previously, the indication for MitraClip in

the United States is limited to degenerative MR. Thebenefit of treating secondary or functional MR re-mains unclear, although some studies from Europehave suggested that treatment does improve func-tional status as well as parameters of left ventricularfunction. The COAPT (Cardiovascular OutcomesAssessment of the MitraClip Percutaneous Therapyfor Heart Failure Patients with Functional Mitral

Regurgitation) trial, designed to test the safety andeffectiveness of the transcatheter device to treatfunctional MR in symptomatic heart failure patientson optimal therapy, is currently underway and willhopefully answer this question (NCT01626079).

The adoption of MitraClip into the treatment al-gorithm has gradually increased in the United Statessince its commercial approval in 2013. However, thereremain significant anatomic limitations to this device.There are a multitude of other transcatheter therapiesthat are in development to either repair or replace theMV and more effectively reduce the regurgitation. Acomprehensive review of these therapies is beyondthe scope of this manuscript. However, initial feasi-bility trials with several of devices have beenencouraging and pivotal trials are being initiated(102,103). Whether these therapies will provide clin-ical benefit beyond MitraClip remains to be seen.Each of these therapies will have different risk pro-files and impact the left ventricle differently. There-fore, randomized studies demonstrating clinicalbenefit and not simply reduction in MR will beneeded.

Transcatheter treatment of TR remains a field in itsinfancy. There is great clinical interest in developingeffective transcatheter therapies, as surgical optionsare limited. Currently there are no U.S. Food and DrugAdministration–approved devices. However, theMitraClip has been used in the tricuspid position withlimited success. A recent registry demonstrated a>50% reduction in effective regurgitant orifice area,associated with significant improvement in New YorkHeart Association (NYHA) functional class and 6-minwalking distance (104). In addition, there are severalother transcatheter therapies targeting TR in feasi-bility trials, including the Trialign system (Mitralign,Tewksbury, Massachusetts) that mimics the surgicalKay annuloplasty via a pair of pledgeted suturesdelivered percutaneously through the right internaljugular vein. The SCOUT (Percutaneous TricuspidValve Annuloplasty System for Symptomatic ChronicFunctional Tricuspid Regurgitation) trial (105) testedthe Trialign system in 15 elderly patients of mean 73.2� 6.9 years of age with NYHA functional class $II andmoderate or greater functional TR. The studydemonstrated significant reductions in tricuspidannulus diameter and effective regurgitant orificearea with significant increase in left ventricular strokevolume. Further feasibility studies are being done toevaluate whether device modifications allowing theuse of multiple pledgets will improve the acute re-sults. The TriCinch device (4Tech Cardio, Galway,Ireland) is designed to reduce annular diameter andTR via a tether applying tension between the anterior

J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8 Kodali et al.M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2 Valvular Heart Disease in the Elderly

2069

tricuspid annulus and a stent, which is anchored inthe inferior vena cava (106). The PREVENT (Percuta-neous Treatment of Tricuspid Valve RegurgitationWith the TriCinch System) registry study is currentlyassessing the safety and potential efficacy of thisdevice (NCT02098200). The FORMA Repair System(Edwards Lifesciences, Irvine, California) is anotherdevice that was examined in 30 elderly patients withsevere TR and NYHA functional class II to IV whowere high risk and declined for surgery. The studydemonstrated both safety and feasibility of this de-vice (107). Similar to what was seen in the SCOUTtrial, there was an w50% in TR severity that wasassociated with an improvement in NYHA functionalclass and 6-min walk distance. Further feasibilitytrials with this device will be initiated after devicemodifications designed to improved efficacy arecompleted.

One of the challenges in evaluating transcathetertricuspid devices remains assessing what constitutesan adequate result. The current “repair” devices willnot reduce TR completely. However, if clinical mea-sures, such as 6-min walk distance, improve and theRV remodels favorably, is that an adequate result,especially in an octogenarian? In the end, studies willhave to have to demonstrate sustained clinical benefitto warrant adoption. A single approach may not workfor patients with TR and MR. The etiologies, as well asanatomic constraints, vary significantly from patientto patient. In some patients, therapy with twodevices, such as the MitraClip and an annuloplastydevice, may be the most effective solution.

The emergence of transcatheter therapies hasraised an important treatment dilemma with regardto coronary artery disease, which can coexist withvalve disease in many octogenarians. Whereas withsurgical valve therapy, significant coronary diseasewould be treated simultaneously with coronary arterybypass grafting, the same may not be true for trans-catheter therapies. An important question to answerin this population is whether treating significantcoronary artery disease improves outcomes. The risksof treatment, as well as the consequences of startingelderly patients on dual antiplatelet therapy, have ledmany to ignore significant coronary artery disease infavor of treating the symptomatic valvular lesion.However, several recent studies have shown thatwhile patients with severe coronary artery disease(SYNTAX score >22) have similar outcomes at30 days, the prognosis is worse at 1 year whencompared with those without severe coronary arterydisease (108,109). The appropriate treatment algo-rithm for how to manage these patients is not yetclear and requires further study. Multiple factors

must be taken into consideration including severityof disease, baseline left ventricular function, volumestatus, and TAVR device being utilized.

The emergence of transcatheter valve therapy hasbeen a “disruptive force” in the treatment paradigmfor VHD. This is especially true for the oldest old, inwhom the goals of treatment may be different. Formany of these patients, survival benefit is not theprimary goal of treatment. In a recent study of pa-tients undergoing TAVR (mean 84 years of age), only7% stated that improved survival was their reasonfor seeking treatment (110). For the majority of pa-tients, maintaining independence (30%) or the abil-ity to do a specific activity (48%) was the reasonprovided. Due to the prolonged recovery periodassociated with surgery, many octogenarians wouldnot come forward for treatment if the only optionwas SAVR. The U.S. experience with TAVR illustratesthis well. In 2012 (the year after TAVR wasapproved), there were 28,778 SAVRs in the STS reg-istry and 4,612 TAVRs in the TVT registry. In 2016,the numbers were 28,037 and 37,113, respectively.This represents 31,760 more patients with AS treateddue to the availability and dissemination of a lessinvasive option. The risk-benefit paradigm changesdramatically when the therapy is less invasive.Considerations such as potentially less durabilitywith TAVR than SAVR play less of a role for octo-genarians, whose expected survival is <10 years.Incorporating patient preferences into the heartteam decision-making process is an importantconsideration, especially in the elderly. The chal-lenge remains explaining the risk-benefit profile ofthe various interventions including TAVR, SAVR,and medical therapy to an elderly patient populationin a manner that is easily understandable. Engagingfamily members in the conversation, especially thoseinvolved in patient care, is important. Also, under-standing the patients’ and family’s treatment goals,which may not be the same, is critical to thedecision-making process (Central Illustration). Asnoted previously, the use of pictorial aids can help.In the elderly, this process can take significant timeand multiple visits, but it is crucial to achieving thebest outcome possible for the patient.

CONCLUSIONS

Severe VHD in the elderly is associated with poorprognosis and reduced survival. Although surgicalmanagement remains the mainstay of therapy, it isassociated with increased risk of morbidity and mor-tality in this age group. Transcatheter therapies are analternative in such patients with multiple comorbid

Kodali et al. J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8

Valvular Heart Disease in the Elderly M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2

2070

conditions with a goal toward symptom relief in most.These therapies will continue to evolve with thedevelopment and refinement of technology, identifi-cation of appropriate patient populations, andimprovement in operator skills and periproceduralmanagement.

ADDRESS FOR CORRESPONDENCE: Dr. Susheel K.Kodali, Columbia University Medical Center, NewYork-Presbyterian Hospital, 177 Fort WashingtonAvenue, New York, New York 10032. E-mail: skodali@columbia.edu.

RE F E RENCE S

1. The Next Four Decades: The Older Population inthe United States 2010 to 2050. Current Popula-tion Reports. May 2010. Available at: https://www.census.gov/prod/2010pubs/p25-1138.pdf.Accessed August 1, 2017.

2. Nkomo VT, Gardin JM, Skelton TN,Gottdiener JS, Scott CG, Enriquez-Sarano M.Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005–11.

3. Iung B, Baron G, Butchart EG, et al.A prospective survey of patients with valvularheart disease in Europe: the Euro Heart Survey onValvular Heart Disease. Eur Heart J 2003;24:1231–43.

4. Singh JP, Evans JC, Levy D, et al. Prevalenceand clinical determinants of mitral, tricuspid, andaortic regurgitation (the Framingham HeartStudy). Am J Cardiol 1999;83:897–902.

5. Nishimura RA, Otto CM, Bonow RO, et al. 2017AHA/ACC Focused Update of the 2014 AHA/ACCGuideline for the Management of Patients WithValvular Heart Disease. A Report of the AmericanCollege of Cardiology/American Heart AssociationTask Force on Clinical Practice Guidelines 2017.Circulation 2017;135:e1159–95.

6. Pretre R, Turina M. Cardiac valve surgery in theoctogenarian. Heart 2000;83:116–21.

7. Cheitlin MD, Gerstenblith G, Hazzard WR, et al.Database Conference January 27–30, 2000,Washington D.C.–Do existing databases answerclinical questions about geriatric cardiovasculardisease and stroke? Am J Geriatr Cardiol 2001;10:207–23.

8. Aziz S, Grover FL. Cardiovascular surgery in theelderly. Cardiol Clin 1999;17:213–31.

9. Khan JH, McElhinney DB, Hall TS, Merrick SH.Cardiac valve surgery in octogenarians: improvingquality of life and functional status. Arch Surg1998;133:887–93.

10. Desai MY, Gerstenblith G. Valvular heart dis-ease in the elderly. In: Gerstenblith G, editor.Cardiovascular Disease in the Elderly. Totowa, NJ:Humana Press, 2005:231–59.

11. Green P, Rosner GF, Schwartz A. Valvular heartdisease in older adults: evolving technology tomeet the needs of aging patients. Aging Health2013;9:205–15.

12. Leon MB, Smith CR, Mack M, et al. Trans-catheter aortic-valve implantation for aortic ste-nosis in patients who cannot undergo surgery.N Engl J Med 2010;363:1597–607.

13. Hughes GH, Cutter G, Donahue R, et al.Recruitment in the Coronary Artery Disease RiskDevelopment in Young Adults (Cardia) study.Control Clin Trial 1987;8:68s–73s.

14. The Atherosclerosis Risk in Communities(ARIC) Study: design and objectives. The ARICinvestigators. Am J Epidemiol 1989;129:687–702.

15. Fried LP, Borhani NO, Enright P, et al. TheCardiovascular Health Study: design and rationale.Ann Epidemiol 1991;1:263–76.

16. Lindman BR, Clavel MA, Mathieu P, et al.Calcific aortic stenosis. Nat Rev Dis Primers 2016;2:16006.

17. Varadarajan P, Sharma S, Heywood JT, Pai RG.High prevalence of clinically silent severe mitralregurgitation in patients with heart failure: role forechocardiography. J Am Soc Echo 2006;19:1458–61.

18. Rossi A, Dini FL, Faggiano P, et al. Independentprognostic value of functional mitral regurgitationin patients with heart failure. A quantitativeanalysis of 1256 patients with ischaemic and non-ischaemic dilated cardiomyopathy. Heart 2011;97:1675–80.

19. Lamas GA, Mitchell GF, Flaker GC, et al. Clin-ical significance of mitral regurgitation after acutemyocardial infarction. Survival and VentricularEnlargement Investigators. Circulation 1997;96:827–33.

20. Grigioni F, Enriquez-Sarano M, Zehr KJ,Bailey KR, Tajik AJ. Ischemic mitral regurgitation:long-term outcome and prognostic implicationswith quantitative Doppler assessment. Circulation2001;103:1759–64.

21. Grigioni F, Tribouilloy C, Avierinos JF, et al.Outcomes in mitral regurgitation due to flailleaflets a multicenter European study. J Am CollCardiol Img 2008;1:133–41.

22. Suri RM, Vanoverschelde JL, Grigioni F, et al.Association between early surgical intervention vs.watchful waiting and outcomes for mitral regur-gitation due to flail mitral valve leaflets. JAMA2013;310:609–16.

23. Lindroos M, Kupari M, Heikkila J, Tilvis R.Prevalence of aortic valve abnormalities in theelderly: an echocardiographic study of a randompopulation sample. J Am Coll Cardiol 1993;21:1220–5.

24. Stewart BF, Siscovick D, Lind BK, et al. Clinicalfactors associated with calcific aortic valve dis-ease. Cardiovascular Health Study. J Am CollCardiol 1997;29:630–4.

25. Eveborn GW, Schirmer H, Heggelund G,Lunde P, Rasmussen K. The evolving epidemiologyof valvular aortic stenosis. The Tromsø study.Heart 2013;99:396–400.

26. Otto CM. Calcification of bicuspid aorticvalves. Heart 2002;88:321–2.

27. Roberts WC, Janning KG, Ko JM, Filardo G,Matter GJ. Frequency of congenitally bicuspidaortic valves in patients >/¼80 years of age un-dergoing aortic valve replacement for aortic ste-nosis (with or without aortic regurgitation) andimplications for transcatheter aortic valve im-plantation. Am J Cardiol 2012;109:1632–6.

28. Osnabrugge RL, Mylotte D, Head SJ, et al.Aortic stenosis in the elderly: disease prevalenceand number of candidates for transcatheter aorticvalve replacement: a meta-analysis and modelingstudy. J Am Coll Cardiol 2013;62:1002–12.

29. Palmieri V, Bella JN, Arnett DK, et al. Aorticroot dilatation at sinuses of valsalva and aorticregurgitation in hypertensive and normotensivesubjects: the Hypertension Genetic EpidemiologyNetwork Study. Hypertension 2001;37:1229–35.

30. Goldbarg SH, Halperin JL. Aortic regurgitation:disease progression and management. Nat ClinCardiovasc Med 2008;5:269–79.

31. Hahn RT, Roman MJ, Mogtader AH,Devereux RB. Association of aortic dilation withregurgitant, stenotic and functionally normalbicuspid aortic valves. J Am Coll Cardiol 1992;19:283–8.

32. Michelena HI, Khanna AD, Mahoney D, et al.Incidence of aortic complications in patients withbicuspid aortic valves. JAMA 2011;306:1104–12.

33. Aronow WS, Kronzon I. Correlation of preva-lence and severity of mitral regurgitation andmitral stenosis determined by Doppler echocardi-ography with physical signs of mitral regurgitationand mitral stenosis in 100 patients aged 62 to 100years with mitral annular calcium. Am J Cardiol1987;60:1189–90.

34. Akram MR, Chan T, McAuliffe S, Chenzbraun A.Non-rheumatic annular mitral stenosis: prevalenceand characteristics. Eur J Echocardiogr 2008;10:103–5.

35. Ukita Y, Yuda S, Sugio H, et al. Prevalence andclinical characteristics of degenerative mitral ste-nosis. J Cardiol 2016;68:248–52.

36. Sugiura M, Uchiyama S, Kuwako K, Ohkawa S,Hiraoka K. A clinicopathological study on mitralring calcification. Japan Heart J 1977;18:154–63.

37. Abramowitz Y, Jilaihawi H, Chakravarty T,Mack MJ, Makkar RR. Mitral annulus calcification.J Am Coll Cardiol 2015;66:1934–41.

38. Codolosa JN, Koshkelashvili N, Alnabelsi T,Goykhman I, Romero-Corral A, Pressman GS. Ef-fect of mitral annular calcium on left ventriculardiastolic parameters. Am J Cardiol 2016;117:847–52.

39. Taramasso M, Vanermen H, Maisano F,Guidotti A, La Canna G, Alfieri O. The growing

J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8 Kodali et al.M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2 Valvular Heart Disease in the Elderly

2071

clinical importance of secondary tricuspid regur-gitation. J Am Coll Cardiol 2012;59:703–10.

40. Michelena HI, Prakash SK, Della Corte A, et al.Bicuspid aortic valve: identifying knowledge gapsand rising to the challenge from the InternationalBicuspid Aortic Valve Consortium (BAVCon). Cir-culation 2014;129:2691–704.

41. Cohen SR, Sell JE, McIntosh CL, Clark RE.Tricuspid regurgitation in patients with acquired,chronic, pure mitral regurgitation. II. Nonoperativemanagement, tricuspid valve annuloplasty, andtricuspid valve replacement. J Thorac CardiovascSurg 1987;94:488–97.

42. Hahn RT. State-of-the-art review of echocar-diographic imaging in the evaluation and treat-ment of functional tricuspid regurgitation. CircCardiovasc Imaging 2016;9:e005332.

43. Rogers JH, Bolling SF. The tricuspid valve.Current perspective and evolving management oftricuspid regurgitation. Circulation 2009;119:2718–25.

44. Girard SE, Nishimura RA, Warnes CA,Dearani JA, Puga FJ. Idiopathic annular dilation: arare cause of isolated severe tricuspid regurgita-tion. J Heart Valve Dis 2000;9:283–7.

45. Topilsky Y, Khanna A, Le Tourneau T, et al.Clinical context and mechanism of functionaltricuspid regurgitation in patients with andwithout pulmonary hypertension. Circ CardiovascImaging 2012;5:314–23.

46. Mahmood F, Kim H, Chaudary B, et al.Tricuspid annular geometry: a three-dimensionaltransesophageal echocardiographic study.J Cardiothorac Vasc Anesth 2013;27:639–46.

47. Nath J, Foster E, Heidenreich PA. Impact oftricuspid regurgitation on long-term survival. J AmColl Cardiol 2004;43:405–9.

48. Stacey D, Hill S, McCaffery K, Boland L,Lewis KB, Horvat L. Shared decision making in-terventions: theoretical and empirical evidencewith implications for health literacy. Stud HealthTechnol Inform 2017;240:263–83.

49. Nishimura RA, Otto CM, Bonow RO, et al. 2014AHA/ACC guideline for the management of pa-tients with valvular heart disease: executive sum-mary: a report of the American College ofCardiology/American Heart Association Task Forceon Practice Guidelines. J Am Coll Cardiol 2014;63:2438–88.

50. Shapira OM, Kelleher RM, Zelingher J, et al.Prognosis and quality of life after valve surgery inpatients older than 75 years. Chest 1997;112:885–94.

51. Collart F, Feier H, Kerbaul F, et al. Valvularsurgery in octogenarians: operative risks factors,evaluation of Euroscore and long term results. EurJ Cardiothorac Surg 2005;27:276–80.

52. Bose AK, Aitchison JD, Dark JH. Aortic valvereplacement in octogenarians. J Cardiothorac Surg2007;2:33.

53. Bakaeen FG, Chu D, Huh J, Carabello BA. Is anage of 80 years or greater an important predictorof short-term outcomes of isolated aortic valvereplacement in veterans? Ann Thorac Surg 2010;90:769–74.

54. Florath I, Albert A, Boening A, Ennker IC,Ennker J. Aortic valve replacement in octogenar-ians: identification of high-risk patients. Eur JCardiothorac Surg 2010;37:1304–10.

55. Molstad P, Veel T, Rynning S. Long-term sur-vival after aortic valve replacement in octogenar-ians and high-risk subgroups. Eur J CardiothoracSurg 2012;42:934–40.

56. Di Eusanio M, Fortuna D, Cristell D, et al.Contemporary outcomes of conventional aorticvalve replacement in 638 octogenarians: insightsfrom an Italian Regional Cardiac Surgery Registry(RERIC). Eur J Cardiothorac Surg 2012;41:1247–52;discussion 1252–3.

57. Bach DS. Prevalence and characteristics ofunoperated patients with severe aortic stenosis.J Heart Valve Dis 2011;20:284–91.

58. Reardon MJ, Van Mieghem NM, Popma JJ,et al. Surgical or transcatheter aortic-valvereplacement in intermediate-risk patients. N EnglJ Med 2017;376:1321–31.

59. Bucerius J, Gummert JF, Walther T, et al.Impact of diabetes mellitus on cardiac surgeryoutcome. Thorac Cardiovasc Surg 2003;51:11–6.

60. Halkos ME, Kilgo P, Lattouf OM, et al. Theeffect of diabetes mellitus on in-hospital andlong-term outcomes after heart valve operations.Ann Thorac Surg 2010;90:124–30.

61. Vives M, Wijeysundera D, Marczin N,Monedero P, Rao V. Cardiac surgery-associatedacute kidney injury. Interac Cardiothorac Surg2014;18:637–45.

62. Fernando M, Paterson HS, Byth K, et al. Out-comes of cardiac surgery in chronic kidney disease.J Thorac Cardiovasc Surg 2014;148:2167–73.

63. Hobson CE, Yavas S, Segal MS, et al. Acutekidney injury is associated with increased long-term mortality after cardiothoracic surgery. Cir-culation 2009;119:2444–53.

64. Helgadottir S, Sigurdsson MI, Ingvarsdottir IL,Arnar DO, Gudbjartsson T. Atrial fibrillationfollowing cardiac surgery: risk analysis and long-term survival. J Cardiothorac Surg 2012;7:87.

65. Mathew JP, Fontes ML, Tudor IC, et al.A multicenter risk index for atrial fibrillation aftercardiac surgery. JAMA 2004;291:1720–9.

66. Filardo G, Hamilton C, Hamman B,Hebeler RF Jr., Adams J, Grayburn P. New-onsetpostoperative atrial fibrillation and long-termsurvival after aortic valve replacement surgery.Ann Thorac Surg 2010;90:474–9.

67. Fried LP, Hadley EC, Walston JD, et al. Frombedside to bench: research agenda for frailty. SciAging Knowledge Environ 2005;2005:pe24.

68. Fried LP, Tangen CM, Walston J, et al. Frailtyin older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci 2001;56:M146–56.

69. Song X, Mitnitski A, Rockwood K. Prevalenceand 10-year outcomes of frailty in older adults inrelation to deficit accumulation. J Am Geratr Soc2010;58:681–7.

70. Sundermann S, Dademasch A, Rastan A, et al.One-year follow-up of patients undergoing elec-tive cardiac surgery assessed with the Compre-hensive Assessment of Frailty test and its

simplified form. Interac Cardiovasc Thorac Surg2011;13:119–23; discussion 123.

71. Afilalo J, Eisenberg MJ, Morin JF, et al. Gaitspeed as an incremental predictor of mortality andmajor morbidity in elderly patients undergoingcardiac surgery. J Am Coll Cardiol 2010;56:1668–76.

72. Adams DH, Popma JJ, Reardon MJ, et al.Transcatheter aortic-valve replacement with aself-expanding prosthesis. N Engl J Med 2014;370:1790–8.

73. Goldstein D, Moskowitz AJ, Gelijns AC, et al.Two-year outcomes of surgical treatment of se-vere ischemic mitral regurgitation. N Engl J Med2016;374:344–53.

74. Silaschi M, Chaubey S, Aldalati O, et al. Ismitral valve repair superior to mitral valvereplacement in elderly patients? Comparison ofshort- and long-term outcomes in a propensity-matched cohort. J Am Heart Assoc 2016;5:e003605.

75. Chikwe J, Goldstone AB, Passage J, et al.A propensity score-adjusted retrospective com-parison of early and mid-term results of mitralvalve repair versus replacement in octogenarians.Eur Heart J 2011;32:618–26.

76. Biancari F, Schifano P, Pighi M, Vasques F,Juvonen T, Vinco G. Pooled estimates of immedi-ate and late outcome of mitral valve surgery inoctogenarians: a meta-analysis and meta-regres-sion. J Cardiovasc Thorac Anesth 2013;27:213–9.

77. Nair CK, Biddle WP, Kaneshige A, Cook C,Ryschon K, Sketch MH, Sr. Ten-year experiencewith mitral valve replacement in the elderly. AmHeart J 1992;124:154–9.

78. Edmunds LH Jr., Stephenson LW, Edie RN,Ratcliffe MB. Open-heart surgery in octogenar-ians. N Engl J Med 1988;319:131–6.

79. Grossi EA, Galloway AC, Zakow PK, et al.Choice of mitral prosthesis in the elderly. Ananalysis of actual outcome. Circulation 1998;98:Ii116–9.

80. De Meester P, Van De Bruaene A, Voigt JU,Herijgers P, Budts W. Outcome and determinantsof prognosis in patients undergoing isolatedtricuspid valve surgery: retrospective single centeranalysis. Int J Cardiol 2014;175:333–9.

81. Smith CR, Leon MB, Mack MJ, et al. Trans-catheter versus surgical aortic-valve replacementin high-risk patients. N Engl J Med 2011;364:2187–98.

82. Kapadia SR, Leon MB, Makkar RR, et al. 5-yearoutcomes of transcatheter aortic valve replace-ment compared with standard treatment for pa-tients with inoperable aortic stenosis (PARTNER1): a randomised controlled trial. Lancet 2015;385:2485–91.

83. Popma JJ, Adams DH, Reardon MJ, et al.Transcatheter aortic valve replacement using aself-expanding bioprosthesis in patients with se-vere aortic stenosis at extreme risk for surgery.J Am Coll Cardiol 2014;63:1972–81.

84. Leon MB, Smith CR, Mack MJ, et al. Trans-catheter or surgical aortic-valve replacement inintermediate-risk patients. N Engl J Med 2016;374:1609–20.

Kodali et al. J A C C V O L . 7 1 , N O . 1 8 , 2 0 1 8

Valvular Heart Disease in the Elderly M A Y 8 , 2 0 1 8 : 2 0 5 8 – 7 2

2072

85. Reardon MJ, Adams DH, Kleiman NS, et al.2-year outcomes in patients undergoing surgicalor self-expanding transcatheter aortic valvereplacement. J Am Coll Cardiol 2015;66:113–21.

86. Thourani VH, Kodali S, Makkar RR, et al.Transcatheter aortic valve replacement versussurgical valve replacement in intermediate-riskpatients: a propensity score analysis. Lancet2016;387:2218–25.

87. Hermiller JB Jr., Yakubov SJ, Reardon MJ,et al. Predicting early and late mortality aftertranscatheter aortic valve replacement. J Am CollCardiol 2016;68:343–52.

88. Maniar HS, Lindman BR, Escallier K, et al.Delirium after surgical and transcatheter aortic valvereplacement is associated with increased mortality.J Thorac Cardiovasc Surg 2016;151:815–23.e2.

89. Mack MC, Szerlip M, Herbert MA, et al. Out-comes of treatment of nonagenarians with severeaortic stenosis. Ann Thorac Surg 2015;100:74–80.

90. Yamamoto M, Mouillet G, Meguro K, et al.Clinical results of transcatheter aortic valve im-plantation in octogenarians and nonagenarians:insights from the FRANCE-2 registry. Ann ThoracSurg 2014;97:29–36.

91. Kayatta MO, Thourani VH, Jensen HA, et al.Outcomes for transcatheter aortic valve replace-ment in nonagenarians. Ann Thorac Surg 2015;100:1261–7.

92. Arsalan M, Szerlip M, Vemulapalli S, et al.Should transcatheter aortic valve replacement beperformed in nonagenarians?: Insights from theSTS/ACC TVT registry. J Am Coll Cardiol 2016;67:1387–95.

93. Deeb GM, Chetcuti SJ, Reardon MJ, et al.1-year results in patients undergoing transcatheteraortic valve replacement with failed surgical bio-prostheses. J Am Coll Cardiol Intv 2017;10:1034–44.

94. Webb JG, Mack MJ, White JM, et al. Trans-catheter aortic valve implantation within degen-erated aortic surgical bioprostheses: PARTNER 2

valve-in-valve registry. J Am Coll Cardiol 2017;69:2253–62.

95. Douglas PS, Leon MB, Mack MJ, et al. Longi-tudinal hemodynamics of transcatheter and sur-gical aortic valves in the PARTNER trial. JAMACardiol 2017;2:1197–206.

96. Mirabel M, Iung B, Baron G, et al. What are thecharacteristics of patients with severe, symptom-atic, mitral regurgitation who are denied surgery?Eur Heart J 2007;28:1358–65.

97. Nishimura RA, Vahanian A, Eleid MF, Mack MJ.Mitral valve disease–current management andfuture challenges. Lancet 2016;387:1324–34.

98. Feldman T, Foster E, Glower DD, et al.Percutaneous repair or surgery for mitral regurgi-tation. N Engl J Med 2011;364:1395–406.

99. Scandura S, Capranzano P, Caggegi A, et al.Percutaneous mitral valve repair with the Mitra-Clip system in the elderly: One-year outcomesfrom the GRASP registry. Int J Cardiol 2016;224:440–6.

100. Alozie A, Paranskaya L, Westphal B, et al.Clinical outcomes of conventional surgery versusMitraClip� therapy for moderate to severesymptomatic mitral valve regurgitation in theelderly population: an institutional experience.BMC Cardiovasc Dis 2017;17:85.

101. Buzzatti N, Maisano F, Latib A, et al. Com-parison of outcomes of percutaneous MitraClipversus surgical repair or replacement for degen-erative mitral regurgitation in octogenarians. Am JCardiol 2015;115:487–92.

102. Bapat V, Rajagopal V, Meduri C, et al. Earlyexperience with new transcatheter mitral valvereplacement. J Am Coll Cardiol 2018;71:12–21.

103. Muller DW, Farivar RS, Jansz P, et al. Trans-catheter mitral valve replacement for patientswith symptomatic mitral regurgitation: a globalfeasibility trial. J Am Coll Cardiol 2017;69:381–91.

104. Nickenig G, Kowalski M, Hausleiter J, et al.Transcatheter treatment of severe tricuspid

regurgitation with the edge-to-edge MitraCliptechnique. Circulation 2017;135:1802–14.

105. Hahn RT, Meduri CU, Davidson CJ, et al. Earlyfeasibility study of a transcatheter tricuspid valveannuloplasty: SCOUT trial 30-day results. J AmColl Cardiol 2017;69:1795–806.

106. Latib A, Agricola E, Pozzoli A, et al.First-in-man implantation of a tricuspid annularremodeling device for functional tricuspidregurgitation. J Am Coll Cardiol Intv 2015;8:e211–4.

107. Kodali S. FORMA: 30-day outcomes oftranscatheter TV repair in patients with severesecondary tricuspid regurgitation. Paper presentedat: Transcatheter Cardiovascular Therapeutics;November 2, 2017; Denver, Colorado.

108. O’Sullivan CJ, Englberger L, Hosek N, et al.Clinical outcomes and revascularization strategiesin patients with low-flow, low-gradient severeaortic valve stenosis according to the assignedtreatment modality. J Am Coll Cardiol Intv 2015;8:704–17.

109. Witberg G, Regev E, Chen S, et al. Theprognostic effects of coronary disease severity andcompleteness of revascularization on mortality inpatients undergoing transcatheter aortic valvereplacement. J Am Coll Cardiol Intv 2017;10:1428–35.

110. Coylewright M, Palmer R, O’Neill ES, Robb JF,Fried TR. Patient-defined goals for the treatmentof severe aortic stenosis: a qualitative analysis.Health Expect 2016;19:1036–43.

111. Maisano F, La Canna G, Colombo A, Alfieri O.The evolution from surgery to percutaneousmitral valve interventions: the role of the edge-to-edge technique. J Am Coll Cardiol 2011;58:2174–82.

KEY WORDS elderly, regurgitation,stenosis, transcatheter technology, valvularheart disease