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ORIGINAL INVESTIGATIONS

Should Transcatheter Aortic ValveReplacement Be Performedin Nonagenarians?

Insights From the STS/ACC TVT Registry

Mani Arsalan, MD,a,b Molly Szerlip, MD,a Sreekanth Vemulapalli, MD,c Elizabeth M. Holper, MD,a

Suzanne V. Arnold, MD,d Zhuokai Li, PHD,c Michael J. DiMaio, MD,a John S. Rumsfeld, MD,e

David L. Brown, MD,a Michael J. Mack, MDa

ABSTRACT

Fro

Ins

Ce

(ST

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BACKGROUND Data demonstrating the outcome of transcatheter aortic valve replacement (TAVR) in the very elderly

patients are limited, as they often represent only a small proportion of the trial populations.

OBJECTIVES The purpose of this study was to compare the outcomes of nonagenarians to younger patients

undergoing TAVR in current practice.

METHODS We analyzed data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter

Valve Therapy) Registry. Outcomes at 30 days and 1 year were compared between patients $90 years versus <90 years

of age using cumulative incidence curves. Quality of life was assessed with the 12-item Kansas City Cardiomyopathy

Questionnaire.

RESULTS Between November 2011 and September 2014, 24,025 patients underwent TAVR in 329 participating

hospitals, of which 3,773 (15.7%) were age $90 years. The 30-day and 1-year mortality rates were significantly higher

among nonagenarians (age $90 years vs. <90 years: 30-day: 8.8% vs. 5.9%; p < 0.001; 1 year: 24.8% vs. 22.0%;

p < 0.001, absolute risk: 2.8%, relative risk: 12.7%). However, nonagenarians had a higher mean Society of Thoracic

Surgeons Predicted Risk of Operative Mortality score (10.9% vs. 8.1%; p < 0.001) and, therefore, had similar ratios of

observed to expected rates of 30-day death (age $90 years vs. <90 years: 0.81, 95% confidence interval: 0.70 to

0.92 vs. 0.72, 95% confidence interval: 0.67 to 0.78). There were no differences in the rates of stroke, aortic valve

reintervention, or myocardial infarction at 30 days or 1 year. Nonagenarians had lower (worse) median Kansas City

Cardiomyopathy Questionnaire scores at 30 days; however, there was no significant difference at 1 year.

CONCLUSIONS In current U.S. clinical practice, approximately 16% of patients undergoing TAVR are$90 years of age.

Although 30-day and 1-year mortality rates were statistically higher compared with younger patients undergoing TAVR,

the absolute and relative differences were clinically modest. TAVR also improves quality of life to the same degree in

nonagenarians as in younger patients. These data support safety and efficacy of TAVR in select very elderly patients.

(J Am Coll Cardiol 2016;67:1387–95) © 2016 by the American College of Cardiology Foundation.

m aThe Heart Hospital Baylor Plano, Plano, Texas; bKerckhoff Heart-Center, Bad Nauheim, Germany; cDuke Clinical Research

titute, Durham, North Carolina; dSaint Luke’s Mid America Heart Institute, Kansas City, Missouri; and the eDenver VA Medical

nter, Denver, Colorado. The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy

S/ACC TVT) Registry is an initiative of the Society of Thoracic Surgeons and the American College of Cardiology. This research

s supported by the American College of Cardiology’s National Cardiovascular Data Registry (NCDR). The views expressed in this

ABBR EV I A T I ON S

AND ACRONYMS

AS = aortic stenosis

CI = confidence interval

IRB = institutional review

board

KCCQ-12 = 12-item Kansas City

Cardiomyopathy Questionnaire

KCCQ-os = overall summary

score of the 12-item Kansas City

Cardiomyopathy Questionnaire

MI = myocardial infarction

QOL = quality of life

TAVR = transcatheter aortic

valve replacement

paper repre

societies id

received re

consultant

member of

other autho

Manuscript

Arsalan et al. J A C C V O L . 6 7 , N O . 1 2 , 2 0 1 6

TAVR in Nonagenarians M A R C H 2 9 , 2 0 1 6 : 1 3 8 7 – 9 5

1388

I t is estimated that the number ofpeople age $90 years (nonagenarians)in the United States will quadruple by

the year 2050 to reach 8.7 million (1). Assuch, clinicians are being confronted withan increasing number of nonagenarianswith severe aortic stenosis (AS), whichsignificantly reduces quality of life and sur-vival. Due to the morbidity and mortality ofsurgical aortic valve replacement in patientsat advanced age, surgery is often denied tovery elderly patients (2,3). Over the last10 years, transcatheter aortic valve replace-ment (TAVR) has emerged as a viable treat-ment option for patients with severe AS

who are inoperable or at high surgical risk, prolongingsurvival and improving quality of life in the majorityof patients (4,5). However, the effect of TAVR in no-nagenarians is largely unknown, as they representonly a small fraction of patients enrolled in thepivotal clinical trials. A few small, single-center serieshave reported outcomes of TAVR in the very elderlyand showed acceptable results (6–9). Due to thislack of outcomes data for TAVR in the very elderly,decision-making for TAVR in nonagenarians iscomplicated. As such, the aim of this study was tocompare the procedural, 30-day, and 1-year outcomesof nonagenarians with patients age <90 years under-going TAVR in current clinical practice using compre-hensive data from the STS/ACC (Society of ThoracicSurgeons/American College of Cardiology) TVT(Transcatheter Valve Therapy) Registry.

SEE PAGE 1396

METHODS

THE STS/ACC TVT REGISTRY. The TVT Registrycollects clinical information including patient demo-graphics, comorbidities, functional status, qualityof life, and procedural details in addition topost-operative, 30-day, and 1-year outcomes usingstandardized definitions on virtually all patientsundergoing TAVR with a commercially approveddevice in the United States (10,11). The ChesapeakeCentral Institutional Review Board (IRB) and theDuke University School of Medicine IRB approved the

sent those of the author(s) and do not necessarily represent the of

entified at CVQuality.ACC.org/NCDR. Dr. Szerlip has served as a s

search grants from Abbott Vascular, Boston Scientific, and the Am

to Boston Scientific and Asahi Intecc. Dr. Rumsfeld is Chief Scienc

the executive committee of the PARTNER (Placement of Aortic T

rs have reported that they have no relationships relevant to the

received November 4, 2015; revised manuscript received Januar

registry. Both IRB committees granted a waiver ofinformed consent and authorization for this study.

STUDY COHORT. Nonagenarians were defined aspatients age $90 years at the time of the procedure,and a small number of centenarians were included inthis study (n ¼ 24). TVT Registry clinical records forprocedures performed from November 2011 throughSeptember 2014 were linked to Medicare administra-tive claims using direct patient identifiers (name andsocial security number) by the Centers for Medicare &Medicaid Services (CMS). Per the CMS NationalCoverage Determination for reimbursement, allpatients were required to have site documentation ofechocardiographically defined severe AS and anassessment by 2 cardiothoracic surgeons who inde-pendently deemed the patients as at high or prohib-itive surgical risk of mortality from surgical aorticvalve replacement. Of the 24,025 index TVT proce-dure records, 8,502 were not linked to Medicare,either because of patient nonparticipation in theMedicare Parts A and B fee-for-service program at thetime of the index procedure or an inability to linkthe index admission to a Medicare inpatient claim.For quality of life, the study cohort was limited toprocedures performed on or before July 17, 2014, for30-day assessment and procedures on or beforeAugust 1, 2013, for 1-year assessment to allow forappropriate follow-up.

STUDY ENDPOINTS. Primary outcomes studiedincluded death, stroke, rehospitalization due to heartfailure, aortic valve reintervention, myocardialinfarction (MI), and quality of life (QOL) at 30 daysand 1 year. QOL was assessed with the 12-item KansasCity Cardiomyopathy Questionnaire (KCCQ-12), a12-item condensed psychometrically valid version ofthe full Kansas City Cardiomyopathy Questionnaire(KCCQ) (12). A disease-specific health status surveyoriginally developed to describe and monitor healthstatus in patients with heart failure, the KCCQ hasalso been validated in patients with aortic stenosis(13). For this study, we focused on the overall sum-mary score of the 12-item Kansas City Cardiomyopa-thy Questionnaire (KCCQ-os), which ranges from 0 to100 with higher scores indicating less symptomburden, less physical and social limitations, and bet-ter quality of life.

ficial views of the NCDR or its associated professional

peaker for Edwards Lifesciences. Dr. Vemulapalli has

erican College of Cardiology. Dr. Holper has been a

e Officer of the NCDR. Dr. Mack is an uncompensated

ranscatheter Valve) trial of Edwards Lifesciences. All

contents of this paper to disclose.

y 14, 2016, accepted January 19, 2016.

TABLE 1 Baseline Characteristics of the Study Population

Nonagenarians(Age $90 yrs)(n ¼ 3,773)

Others(Age <90 yrs)(n ¼ 20,252) p Value

Age, yrs 92.0 (90.0–93.0) 82.0 (76.0–86.0) <0.001

Female 1,953 (51.76) 9,976 (49.26) 0.005

STS PROM score 9.22 (6.73–13.25) 6.34 (4.20–9.77) <0.001

NYHA functional class I and II 670 (17.76) 3,459 (17.08) 0.347

NYHA functional class III and IV 3,055 (80.97) 16,479 (81.37)

LVEF 58.00 (48.00–65.00) 56.00 (45.00–63.00) <0.001

Prior CABG 693 (18.37) 6,873 (33.94) <0.001

Prior other cardiac surgery 150 (3.98) 1,477 (7.29) <0.001

Prior aortic valve procedure 646 (17.12) 3,239 (15.99) 0.086

Permanent pacemaker/ICD 817 (21.65) 3,209 (15.85) <0.001

Atrial fibrillation 1,619 (42.91) 8,175 (40.37) 0.004

Prior stroke 352 (9.33) 2,587 (12.77) <0.001

Transient ischemic attack 394 (10.44) 1,719 (8.49) <0.001

Peripheral arterial disease 970 (25.71) 6,606 (32.62) <0.001

Hypertension 3,266 (86.56) 18,077 (89.26) <0.001

Diabetes mellitus 730 (19.35) 8,179 (40.39) <0.001

Insulin-dependent diabetes 149 (20.41) 3,192 (39.03) <0.001

Moderate-severe chronic lung disease 581 (15.40) 6,096 (30.10) <0.001

Prior MI 786 (20.83) 5,258 (25.96) <0.001

5-m walk test time, s 8.67 (6.67–11.33) 8.00 (6.00–10.67) <0.001

KCCQ-12 overall score 41.67 (23.96–59.38) 37.50 (21.88–56.77) <0.001

BMI, kg/m2 24.67 (22.20–27.56) 27.25 (23.88–31.77) <0.001

Currently on dialysis 39 (1.03) 945 (4.67) <0.001

Creatinine, mg/dl 1.10 (0.90–1.40) 1.10 (0.90–1.50) 0.002

Triple-vessel disease 786 (20.83) 5,709 (28.19) <0.001

Left main stenosis $50% 325 (8.61) 2,241 (11.07) <0.001

Moderate-severe aortic insufficiency 663 (17.57) 4,171 (20.60) <0.001

Values are median (interquartile range) or n (%).

BMI ¼ body mass index; CABG ¼ coronary artery bypass grafting; KCCQ-12 ¼ 12-item Kansas CityCardiomyopathy Questionnaire; ICD ¼ implantable cardioverter-defibrillator; LVEF ¼ left ventricular ejectionfraction; MI ¼ myocardial infarction; NYHA ¼ New York Heart Association; STS PROM ¼ STS Predicted Risk ofOperative Mortality.

J A C C V O L . 6 7 , N O . 1 2 , 2 0 1 6 Arsalan et al.M A R C H 2 9 , 2 0 1 6 : 1 3 8 7 – 9 5 TAVR in Nonagenarians

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In-hospital outcomes were collected as part of theTVT Registry. Valve Academic Research Consortiumdefinitions were used for major bleeding (10,11). Allsite-reported stroke and valve reintervention eventswere adjudicated by a board-certified cardiologistusing Valve Academic Research Consortium defini-tions. This process involved review of specific sitequeries and de-identified source records as needed.Following hospital discharge, death was identifiedusing the Medicare Denominator file. Medicarein-hospital administrative claims files were used fordetection of re-hospitalization events throughOctober 2014 using the following International Clas-sification of Diseases, Ninth Revision, Clinical Modi-fication codes: for stroke; 433.x1, 434.x1, 997.02, 436,437.1, 437.9, 430, 431, and 432.x; for heart failure,398.x, 402.x1, 404.x1, 404.x3, and 428.x; for aorticvalve reintervention, 35.11, 35.21, 35.22, 35.01, 35.05,35.06, and 35.09; and for MI, 410.x0 and 410.x1.For rehospitalization, follow-up was censored at theend of fee-for-service coverage, loss of Part A or Bcoverage, or end of the follow-up period (October 31,2014), whichever occurred first.

STATISTICAL ANALYSIS. Baseline characteristicsand in-hospital outcomes of the study populationwere presented according to age. Categorical vari-ables were summarized as percentages, and contin-uous variables as medians with interquartile ranges.The baseline characteristics and in-hospital outcomesof patients $90 and <90 years of age were thencompared using the Pearson chi-square test for cate-gorical variables and the Wilcoxon rank sum test forcontinuous variables.

Cumulative incidences of death and nonfatal out-comes at 30 days and 1 year post-TAVR were esti-mated for patients $90 and <90 years of age. Fornonfatal outcomes, including stroke, heart failurereadmission, aortic valve reintervention and post-procedural MI, death was considered a competingrisk, and therefore the cumulative incidence indi-cated the probability of a nonfatal outcome occurringgiven that death may impede its occurrence (14). The30-day observed-to-expected mortality ratios werecalculated on the basis of the baseline Societyof Thoracic Surgeons Predicted Risk of OperativeMortality (STS PROM) score, with 95% confidenceintervals (CIs) obtained using a normal approxima-tion to the binomial distribution (15).

The Cox proportional hazards models were used toassess the unadjusted and adjusted effects of age on30-day and 1-year mortality. Nonfatal outcomes wereassessed using Fine and Gray proportional sub-distribution hazards models in the presence of

competing risk of death (14,16). The multivariablemodels included the covariates in the recentlydeveloped TVT model for in-hospital mortality (un-published data). The risk of adverse outcomes forpatients $90 years versus <90 years of age was re-ported using hazard ratios (HRs) with 95% CIs.

Complete case analysis was performed for 30-dayand 1-year KCCQ-os scores. KCCQ-os scores weresummarized as medians with interquartile ranges andcompared between patients $90 and <90 years of ageusing the Wilcoxon rank sum test. The effect of ageon follow-up KCCQ-os scores was assessed usinglinear regression models that included a binary indi-cator variable for age group. Models were constructedas unadjusted (including age only) and adjusted,including age, baseline STS PROM score, and baselineKCCQ-os score. As the STS PROM score is calculatedincluding age as well as its interactions with severalrisk factors, this complicates the multivariableadjustment. As such, the baseline STS PROM score

TABLE 2 In-Hospital Outcomes of Nonagenarians and Patients Age <90 Years

Nonagenarians(Age $90 yrs)(n ¼ 3,773)

Others(Age <90 yrs)(n ¼ 20,252) p Value

Myocardial infarction 25 (0.67) 104 (0.52) 0.248

Stroke 102 (2.72) 426 (2.11) 0.021

Atrial fibrillation 258 (6.87) 1,320 (6.54) 0.458

Major vascular access site complication 38 (1.01) 133 (0.66) 0.019

Minor vascular access site complication 82 (2.18) 353 (1.75) 0.068

New requirement for dialysis 60 (1.60) 373 (1.85) 0.289

Aortic valve reintervention 10 (0.27) 73 (0.36) 0.361

VARC major bleeding event 299 (8.11) 1,354 (6.81) 0.004

In-hospital mortality 244 (6.47) 915 (4.52) <0.001

Discharge location home 1,848 (52.38) 12,793 (66.19) <0.001

Extended care/TCU/rehab 1,319 (37.39) 5,317 (27.51)

Nursing home 296 (8.39) 922 (4.77)

Other 62 (1.76) 279 (1.44)

RBC/whole blood transfusion 1,690 (44.79) 7,753 (38.28) <0.001

Length of stay, days 6.00 (4.00–10.00) 6.00 (4.00–9.00) <0.001

Number of hours in ICU 46.00 (24.00–78.00) 44.00 (24.00–74.30) <0.001

Values are n (%) or median (interquartile range).

ICU ¼ intensive care unit; RBC ¼ red blood cells; TCU¼ transitional care unit; VARC¼ Valve Academic ResearchConsortium.

Arsalan et al. J A C C V O L . 6 7 , N O . 1 2 , 2 0 1 6

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was recalculated assuming all patients were 85 yearsof age, the median age of the study population. Allanalyses were performed using SAS software, version9.4 (SAS Institute Inc., Cary, North Carolina), and ap value <0.05 was considered statistically significant.

RESULTS

PATIENT COHORT. From November 2011 throughSeptember 2014, 24,025 patients, of which 3,773(15.7%) were nonagenarians, underwent TAVR at 329participating hospitals. The median age was 92 yearsin nonagenarians and 82 years in the younger cohort.Compared to patients<90 years of age, nonagenarians

TABLE 3 Post-Discharge Outcomes in Nonagenarians and Patients Ag

Nonagenarians (Age $90 yrs) Othe

Outcome Events Rate Events

30-day outcomes

Mortality 232 8.8 (7.8–10.0) 755

Stroke 77 2.9 (2.4–3.7) 305

Heart failure 140 5.3 (4.5–6.3) 548

Aortic valve reintervention 10 0.4 (0.2–0.7) 51

Myocardial infarction 22 0.8 (0.6–1.3) 98

1-year outcomes

Mortality 570 24.8 (23.1–26.7) 2324

Stroke 108 4.4 (3.7–5.4) 456

Heart failure 345 14.9 (13.5–16.5) 1588

Aortic valve reintervention 14 0.6 (0.3–0.9) 75

Myocardial infarction 46 2.0 (1.5–2.7) 230

Values are n or % (95% confidence interval [CI]), unless otherwise indicated.

were more likely to be female and less likely to havehigh-risk features including prior nonaortic valve car-diac surgery procedure, diabetes, prior stroke, andprior MI, but overall, they had higher estimated sur-gical mortality (STS PROM scores, age $90 years vs.<90 years: 9.2% vs. 6.3%; p < 0.001). Although nona-genarians had slower 5-m walk tests (8.7 s vs. 8.0 s;p < 0.001), they had better self-reported QOL (KCCQ-os:41.7 vs. 37.5; p < 0.001) prior to TAVR (Table 1).

IN-HOSPITAL OUTCOMES. Compared with patients<90 years of age, nonagenarians were more likely toexperience in-hospital stroke, major vascular assesssite complications, and major bleeding events(Table 2). They also had longer intensive care unit staysand increased rates of blood transfusions. In-hospitaldeath was higher among nonagenarians (6.5% vs.4.5%; p < 0.001), and they were also more likely tobe discharged to extended care/transitional care unit/rehabilitation or nursing home.

POST-DISCHARGE OUTCOMES. No differences instroke rate, aortic valve reintervention, or MI wereevident after 30 days or 1 year (Table 3, Figures 1and 2). There was a higher rate of heart failurereadmission after 30 days for nonagenarians (5.3% vs.4.3%; p ¼ 0.014) (Figure 3) but not after 1 year (14.9%vs. 14.5%; p ¼ 0.377). The 30-day and 1-year mortalityrates were significantly higher among nonagenarians(age $90 years vs. <90 years: 30-day rate: 8.8%vs. 5.9%; p < 0.001; 1-year rate: 24.8% vs. 22.0%;p < 0.001, absolute risk 2.8%, relative risk 12.7%)(Figure 4). Among the small number of patients whowere $100 years of age (n ¼ 15), 30-day mortality was0% and 1-year mortality was 6.7%.

After adjusting for multiple demographic andclinical factors, nonagenarians continued to show anincreased risk of mortality at 30 days (adjusted HR:

e <90 Years and Unadjusted Hazard Ratios

rs (Age <90 yrs) Unadjusted Hazard Ratio

Rate p Value Hazard Ratio (95% CI) p Value

5.9 (5.5–6.3) <0.001 1.53 (1.32–1.78) <0.001

2.4 (2.1–2.6) 0.087 1.24 (0.97–1.60) 0.087

4.3 (3.9–4.6) 0.014 1.26 (1.05–1.52) 0.014

0.4 (0.3–0.5) 0.912 0.96 (0.49–1.90) 0.913

0.8 (0.6–0.9) 0.683 1.10 (0.69–1.75) 0.683

22.0 (21.2–22.9) <0.001 1.21 (1.11–1.33) <0.001

3.9 (3.6–4.3) 0.183 1.16 (0.94–1.42) 0.178

14.5 (13.8–15.2) 0.377 1.06 (0.94–1.19) 0.354

0.6 (0.5–0.8) 0.738 0.91 (0.51–1.61) 0.741

2.3 (2.0–2.6) 0.783 0.96 (0.70–1.32) 0.804

FIGURE 1 Adjusted Age Effects on Post-Discharge Outcomes

0.4 0.6 0.8 1 1.2 1.6 2

30-Day

Mortality

Stroke

Heart Failure

Aortic Valve Reintervention

MI

1-Year

Mortality

Stroke

Heart Failure

Aortic Valve Reintervention

MI

Adjusted HR(95% CI) p-value

1.46 (1.25, 1.71)

1.13 (0.88, 1.47)

1.35 (1.11, 1.65)

0.90 (0.44, 1.81)

1.15 (0.70, 1.90)

<.001

0.342

0.003

0.761

0.582

1.20 (1.09, 1.32)

1.12 (0.89, 1.39)

1.12 (0.99, 1.27)

0.96 (0.53, 1.73)

1.09 (0.78, 1.53)

<.001

0.332

0.070

0.886

0.610

Adjusted age effects on post-discharge outcomes after 30 days and 1 year. CI ¼ confidence interval; HR ¼ hazard ratio; MI ¼ myocardial

infarction.

FIGURE 2 Stroke

5

4

3

2

1

0

Cum

ulat

ive

Inci

denc

e, %

0 3 6 9 12Months Since Index Procedure

NonagenariansPatients aged < 90

No. of events / No. at riskNonagenarians

Patients aged < 9021 / 262851 / 12895

90 / 1957358 / 9815

98 / 1524408 / 7493

101 / 1225437 / 5895

108 / 999456 / 4730

Cumulative incidence of stroke in nonagenarians and patients younger than age 90 years.

J A C C V O L . 6 7 , N O . 1 2 , 2 0 1 6 Arsalan et al.M A R C H 2 9 , 2 0 1 6 : 1 3 8 7 – 9 5 TAVR in Nonagenarians

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1.46; 95% CI: 1.25 to 1.71; p < 0.001), heart failure at30 days (adjusted HR: 1.35; 95% CI: 1.11 to 1.65;p ¼ 0.003), and mortality at 1 year (adjusted HR: 1.20;95% CI: 1.09 to 1.32; p < 0.001). However, as nona-genarians had a higher STS PROM than the youngercohort, the observed to expected mortality ratioswere 0.81 (95% CI: 0.70 to 0.92) and 0.72 (95% CI: 0.67to 0.78), respectively.

QUALITY OF LIFE. Nonagenarians had a lowermedian 30-day KCCQ-os score compared withyounger patients (70.8 vs. 72.9; p ¼ 0.006) but similarKCCQ-os scores at 1 year after TAVR (79.2 vs. 81.3;p ¼ 0.539) (Table 4). After adjusting for STS PROM riskscore and baseline KCCQ, nonagenarians had, onaverage, 3.57-point lower KCCQ-os scores at 30 daysbut no significant difference at 1 year.

DISCUSSION

This is the largest study comparing short-term andmidterm outcomes of nonagenarians with youngerpatients undergoing TAVR in U.S. clinical practice.Patient demographics of nonagenarians in this studyhighlight that nonagenarians who are currentlyundergoing TAVR represent a highly selected group.Factors that cause a patient to be at higher risk forpoor outcomes after TAVR, such as reduced ejectionfraction, prior cardiac surgery, and prior stroke, areless commonly present in nonagenarians comparedwith the younger population; thus, very advancedage is the primary factor for the nonagenarian to be

classified as high risk for surgery. Although thesepatients are at increased risk for morbidity and mor-tality after TAVR simply on the basis of their age, ourfindings show that many nonagenarians have goodoutcomes after TAVR, with prolonged survival andimproved QOL, making TAVR reasonable to considerin select nonagenarians with severe AS.

Most of the existing studies report on single-centerexperiences with small patient cohorts and thus may

FIGURE 3 Heart Failure Readmission

20

15

10

5

0

Cum

ulat

ive

Inci

denc

e, %

0 3 6 9 12Months Since Index Procedure

No. of events / No. at riskNonagenarians

Patients aged < 900 / 26280 / 12895

241 / 18251054 / 9237

288 / 14001341 / 6914

324 / 11041494 / 5368

345 / 8841588 / 4277

NonagenariansPatients aged < 90

Cumulative incidence of heart failure readmission in nonagenarians and patients younger

than age 90 years.

FIGURE 4 Mortali

30

25

20

15

10

5

0

Cum

ulat

ive

Inci

denc

e, %

No. Nonagenarians

Patients aged < 9039 /

104

Cumulative incidence

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only provide limited decision-making information onthe outcomes of nonagenarians undergoing TAVR(6–9,17). In the largest previous study on TAVR in no-nagenarians (346 nonagenarians of 2,254 enrolled pa-tients; reported from the FRANCE-2 [French NationalTranscatheter Aortic Valve Implantation Registry]),Yamamoto et al. (18) demonstrated a 30-day mortalityof 11.2% in nonagenarians without any significantdifference compared with patients age 80 to 84 years

ty

0 3 6 9 12Months Since Index Procedure

of events / No. at risk 2628

/ 12895378 / 2020

1331 / 10080479 / 1586

1804 / 7765526 / 1288

2093 / 6165570 / 1054

2324 / 4989

NonagenariansPatients aged < 90

of mortality in nonagenarians and patients younger than age 90 years.

or 85 to 89 years (18). We found a lower 30-day mor-tality rate in nonagenarians (8.8%), which may reflectdifferences in patient selection and improvementsin devices and techniques. Although the mortalityrate for nonagenarians in our study remained higherthan that observed in younger patients (5.9%), thisrate may be acceptable, particularly given the QOLbenefits observed among surviving nonagenarians.This is further illustrated by the similar observed-to-expected ratios. Of note, the observed nonagenarianmortality rate is not only lower than that previouslyreported on nonagenarians, but is also comparableto published mortality rates for octogenarians (18,19).

In regard to long-term survival, the FRANCE-2 datashowed a trend toward decreased survival in olderpatients, but the study did not meet statistical signifi-cance due to the limited number of patients at risk by1 year (18). The current study confirms a higher mor-tality rate in nonagenarians at 1 year, but due to thehigh mortality rates in both groups, it is doubtful thatthemeasureddifference of 2.8% is clinically significantor simply reflects the shorter underlying life expec-tancy of nonagenarians. Some clarity on this issuecan be achieved by comparing our 1-year outcomes tothe life expectancy of an age-matched general pop-ulation. The younger patient cohort showed a 1-yearmortality of 22%, which is significantly higher com-pared with the age-matched general population (6.1%in males and 4.4% in females) (20). In nonagenarians,however, the observed difference between 1-yearmortality in TAVR patients (24.8%) and the same-age general population (male 20.5% and female16.5%) was much smaller (Central Illustration).

Thus, we confirm the promising results from otherreports about TAVR in select nonagenarians, and weadditionally show that the difference between out-comes of select nonagenarians and younger patientsmight not be of major clinical relevance.

We further describe the outcomes of a very smallcohort of patients$100 years of age undergoing TAVR.Overall, 24 centenarians were treated in the TVT reg-istry; thus, this is the largest report on TAVR in thisage group. We are aware that our patient cohort(n ¼ 15 with CMS linkage) is too small to give areliable statement, but nevertheless, the proceduraloutcomes are encouraging. There was no mortality at30 days, which is likely indicative of very carefulpatient selection. The very low 1-year mortality(6.7%) is excellent, especially considering the high1-year death probability in a 100-year-old patient(36% in males and 31% in females). Of note, Bridgeset al. (21), reviewing the STS national database, re-ported that only 5 centenarians underwent cardiacsurgery in the United States between 1997 and 2000.

TABLE 4 30-Day and 1-Year KCCQ-12 Overall Summary Scores in Nonagenarians and Others Age <90 Years

Nonagenarians (Age $90 yrs) Others (Age <90 yrs)

p Valuen Mean Median (IQR) n Mean Median (IQR)

30-day KCCQ-os score 1,571 66.25 70.83 (51.04–86.46) 8,686 68.11 72.92 (52.60–87.50) 0.006

1-year KCCQ-os score 623 74.77 79.17 (61.46–93.75) 3,089 75.20 81.25 (62.50–93.75) 0.539

IQR ¼ interquartile range; KCCQ-os ¼ overall summary score of the 12-item Kansas City Cardiomyopathy Questionnaire.

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Increased age alone may heighten the risk of partic-ular post-procedural complications. As vascular com-plications were 1 of the most common complications,assessing age-related differences is relatively straight-forward. The increasing prevalence of vascular com-plications in very old patients has been demonstratedby several studies, but, because of varying definitions,rates of vascular complications are difficult to comparebetween studies. Havakuk et al. (22) reported thatthe rate of minor vascular injuries is increased in pa-tients age $85 years (7.5% vs. 16%; p ¼ 0.02), withoutany difference in major vascular complications (4.3%vs. 2.5%; p ¼ 0.41). However, our data, similar to thoseof Yamamoto et al. (9), shows higher rates of majorvascular complications in the very elderly, but nosignificant difference inminor vascular injury rates.

Additional in-hospital complications that differedbetween nonagenarians and younger patients weremajor bleeding events, need for blood transfusion,and stroke, all of which were higher in the nonage-narian group. The in-hospital stroke rate was higherfor nonagenarians in the present study, but wedid not detect any significant effect of age on inci-dence of stroke following TAVR at 30 days or at 1 year(9,18,22). The observed 30-day stroke rate was similarto prior reports on elderly patients undergoing TAVR(6,9,19,22,23). The increased incidences of these in-hospital complications are comprehensively reflectedin the longer intensive care unit stays and higherlikelihood of discharge to extended care or rehabili-tation facilities experienced by nonagenarians.

Although our in-hospital results might suggestworse short-term outcomes for nonagenarians,30-day and, more importantly, 1-year outcomes aremore suitable to determine the appropriateness ofTAVR in the nonagenarian age group. However, it isimportant to note that survival is not the sole factordefining good outcomes in TAVR, especially in theelderly population where survival with reasonablefunctional capacity and QOL is what matters most.Improvement in QOL should also be included toevaluate whether a procedure should be reasonablyoffered to nonagenarians.

In a review of the PARTNER (Placement of AorticTranscatheter Valve) trial, Thourani et al. (24) have

previously demonstrated that QOL improves andstabilizes 6 months after TAVR in nonagenarians. Ourdata confirm these findings. We found that there wasa significant increase in KCCQ scores by 30 days, butscores were significantly lower in nonagenarianscompared with younger patients. However, therewere no differences in QOL between age groups by 1year after TAVR. These findings suggest that nona-genarians likely recover more slowly after TAVR andthus need more time until the beneficial effect of theprocedure is measurable. However, if given time torecover, older patients are able to achieve similar QOLlevels as younger patients. This information may beimportant for patients to know prior to undergoingTAVR, for post-procedure planning and setting real-istic expectations of recovery times.

STUDY LIMITATIONS. This analysis should be inter-preted in light of several important potential limita-tions. The TVT Registry only captures information onpatients receiving commercially approved devices. Asseveral newer TAVR devices are currently underinvestigation in the United States, our data thus donot represent an all-comers population or the mostrecent iterations of transcatheter devices. Further-more, a large number of patients (35%; 8,502 of 24,025)could not be included in long-term outcome analysisdue to inability to link with the CMS. Compared withpatients without CMS linkage, patients with CMSlinkage were more likely to be females; to have priortransient ischemic attack; and to have higher leftventricular ejection fraction, STS PROM, and KCCQ-12scores. They were less likely to have prior aortic valveprocedure, have diabetes, have New York Heart Asso-ciation functional class III/IV, and be currently ondialysis. Furthermore, there was a high rate of missingKCCQ data (50% at 30-day and 62% at 1-yearfollow-up). Compared with patients with nonmissingKCCQ-os scores, patients with missing KCCQ scores atfollow-up were more likely to be males, have a slower5-m walk test, have lower left ventricular ejectionfraction, have higher STS PROM, have lower baselineKCCQ score, have insulin dependent diabetes, andbe on dialysis. It is unclear how inclusion of thesepatients with missing follow-up data would have

CENTRAL ILLUSTRATION TAVR in Nonagenarians: Mortality, Stroke, and Quality of Life Compared With Patients<90 Years of Age, and Mortality Compared With an Age-Matched General Population

KCCQ-12-os ¼ overall summary score of the 12-item Kansas City Cardiomyopathy Questionnaire; TAVR ¼ transcatheter aortic valve replacement.

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PERSPECTIVES

COMPETENCY IN PATIENT CARE AND PROCEDURAL

SKILLS: Although 30-day and 1-year mortality rates are higher

in nonagenarians undergoing TAVR, the absolute and relative

differences compared with younger patients are clinically modest.

TRANSLATIONAL OUTLOOK: As the indication for TAVR

expands to encompass patients at lower risk, more research is

needed to clarify which patients, regardless of age, benefit most

from the procedure.

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altered our findings. However, our study still repre-sents the largest study of nonagenarians who haveundergone TAVR and provides much needed datato describe the outcomes of these high-risk patients.

CONCLUSIONS

Given their limited life expectancy, it has been unclearwhether to perform TAVR in the very elderly, asexisting data on outcomes of these patients havebeen limited. The primary concerns are that nonage-narians might not survive the procedure as frequently,recover from the procedure as quickly, or experiencean improved functional outcome andquality of life.Wereport in current U.S. clinical practice that approxi-mately 16% of patients undergoing TAVR are nonage-narians or older. Although 30-day and 1-year mortalityrates were higher in this age group compared withyounger TAVR patients, the absolute and relativedifferences were clinically modest. Furthermore,although nonagenarians generally take longer torecover their physical function and QOL than youngerpatients, TAVR improved long-term QOL to a similar

degree in both age groups. As such, the reported datasupport both the safety and the efficacy of TAVR inselect elderly patients, suggesting that TAVR shouldnot be denied solely on the basis of patient age.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.Michael J. Mack, Heart Hospital Baylor Plano, 1100Allied Drive, Plano, Texas 75093. E-mail: MichaeMa@baylorhealth.edu.

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KEY WORDS centenarians, elderly, qualityof life, TAVI, TAVR, transcatheter aortic valveimplantation