Transcatheter Aortic Valve Replacement

Quality of Life Outcomes After Transcatheter Aortic Valve Replacement in Nonagenarians

Houman Khalili, MD1,2; Priya Bansal, MD3; Haider Al Taii, MD3; Ramez Morcos, MD, MBA4; Michael Kucharik, BS1; Adithya Mathews, MD, MBA3; Hamza Lodhi, MD3; Sanjay Chandrasekhar, BS1; Andrew Fahmy, BS1; Divyesh Doddapaneni, BS1; Brijeshwar Maini, MD1,2

Houman Khalili, MD1,2; Priya Bansal, MD3; Haider Al Taii, MD3; Ramez Morcos, MD, MBA4; Michael Kucharik, BS1; Adithya Mathews, MD, MBA3; Hamza Lodhi, MD3; Sanjay Chandrasekhar, BS1; Andrew Fahmy, BS1; Divyesh Doddapaneni, BS1; Brijeshwar Maini, MD1,2

Abstract: Background. Transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) is an increasingly prevalent treatment in patients who are intermediate or high risk for surgical intervention. In nonagenarian patients undergoing TAVR, symptomatic relief and quality of life (QoL) outcomes have not been well established. This study explores these outcomes in this patient population that has been underrepresented in landmark clinical trials. Methods. All patients who underwent TAVR between January 1, 2015 and December 31, 2018 at Delray Medical Center were included. The 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score was used to assess QoL prior to and 30 days following TAVR in two patient groups: the nonagenarian group (patients ≥90 years old) and the younger group (patients <90 years old). KCCQ-OS scores were compared between these two groups. Frailty assessment included grip strength, gait speed, and activities of daily living. Unadjusted and adjusted analyses (baseline KCCQ-OS score, frailty, and Society of Thoracic Surgery perioperative risk of mortality [STS-PROM] score) were performed to assess the impact of age on QoL outcomes in both groups. Results. Of the total 223 patients included in this study, a total of 46 (20.6%) were nonagenarians and 118 (52.7%) were men. KCCQ-OS scores were lower at baseline and 30-day follow-up in nonagenarians compared with the younger group (P=.70). Age was a significant predictor of 30-day KCCQ-OS in unadjusted and adjusted analyses (adjusted for baseline KCCQ-OS, frailty, and STS-PROM score). Nonagenarians had an average 6.45 points lower 30-day KCCQ-OS scores than the younger patients in adjusted analysis. However, there was a significant clinical improvement in the 30-day KCCQ-OS score in both groups (P<.001). Conclusions. Our data suggest that with appropriate patient selection, a significant clinical improvement may be expected with TAVR in nonagenarians. 

J INVASIVE CARDIOL 2020;32(10):375-379. 

Key words: age, outcomes, quality of life


Transcatheter aortic valve replacement (TAVR) is non-inferior to surgical aortic valve replacement for treatment of severe aortic stenosis (AS) in all risk cohorts.1-3 Despite the high procedural success rate and low in-hospital mortality, 25%-30% of patients in early clinical trials who were considered to be at prohibitive risk for surgery had poor outcomes at 1 year post TAVR, including a higher rate of death and worse quality of life (QoL).4-8 Considering the aging population, the prevalence of degenerative severe AS is expected to rise especially in the very elderly.9 Nonagenarians (age ≥90 years old) are an underrepresented age group in the landmark TAVR clinical trials, and only a few retrospective studies have examined outcomes in this population.10-15 Given the lack of adequate data in this patient population, as well as concerns regarding QoL and frailty, there may exist some hesitation in offering TAVR to nonagenarians. The purpose of this study is to evaluate the quality of outcomes and the impact of frailty in nonagenarians undergoing TAVR compared with the younger population.

Methods

Patient population. We conducted a retrospective cohort study of patients undergoing TAVR between January 2015 to December 2018 at Delray Medical Center. Records of all patients undergoing TAVR were screened for eligibility and a comprehensive chart review was performed (RM, MK). 

Briefly, patients eligible for TAVR are those with symptomatic severe AS, aortic valve area <1.0 cm2, aortic valve mean gradient >40 mm Hg, and life expectancy of >1 year, as well as those who are considered to be at moderate, high, or prohibitive risk for surgical aortic valve replacement. Patients were evaluated and discussed by the structural heart team in a collaborative effort between clinical cardiologists, cardiac imaging specialists, interventional cardiologists, and cardiothoracic surgeons for the appropriateness of TAVR. At our institution, general anesthesia and transfemoral access are preferred in the majority of TAVR procedures. Alternative access (transapical, subclavian, and transaortic) TAVRs were excluded from this study. Clinical information, including patient demographics, comorbid conditions, QoL, and frailty scores were collected preoperatively and at 30 days post TAVR. Nonagenarian was defined as age ≥90 years old at the time of TAVR. Only patients with 30-day Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary (OS) scores were included in the QoL analysis. The institutional review board approved the database, granted a waiver of informed consent, and authorized the study. 

Clinical follow-up. Patients were followed at the Structural Heart Clinic at 1 week and 1 month, then every 4 months post TAVR, in addition to routine follow-up exams with the referring cardiologist and primary care provider. QoL was assessed using the KCCQ at baseline and 30 days post discharge. 

The KCCQ score is a disease-specific instrument that was initially designed to describe and monitor health status in patients with heart failure post myocardial infarction.16 It has been extensively studied for reliability and validity in various heart failure populations and has been considered as a good predictor for mortality as well as healthcare costs.17 The shortened 12-item validated version (KCCQ-12) was used in this study.18 Four domain scores and one total score were generated from the KCCQ-12 questionnaire. The KCCQ-OS represented an integration of four domain scores: the patient’s physical limitation (PL), symptom frequency (SF), quality of life (QoL), and social limitation (SL). Scores are scaled from 0-100, where 0 denotes the lowest reportable health status and 100 the highest.19 For this study, we used the KCCQ-OS score.19 Changes in KCCQ-OS of 5, 10, and 20 correspond to small, moderate, and large clinical improvements.20

Study endpoints and statistical analysis. The primary outcome was QoL outcomes at 30 days as assessed by KCCQ. Continuous variables were expressed as means ± standard deviations; categorical variables were expressed as counts and percentages. A bivariate variable was created to define nonagenarians ≥90 years old and other age groups. 

Changes in KCCQ-OS from baseline were evaluated at 30 days using the Wilcoxon rank-sum test. Mean KCCQ-OS and individual KCCQ component scores at 30 days were compared between the two age groups using one-way ANCOVA (a blend of analysis of variance [ANOVA] and regression). This analysis was adjusted for baseline KCCQ scores, Society of Thoracic Surgery perioperative risk of mortality (STS-PROM) score, and frailty score. The frailty score encompasses grip strength, 5-meter gait speed, and activities of daily living (ADL), which include eating, bathing, dressing, toileting, transferring, and maintaining continence. We computed an ordinal categorical variable called “frailty total” with a 0-3 range using the following cut-off points: grip strength <30 kg for men and <20 kg for women; 5-meter gait speed >6 seconds; and ADL ≤4. A higher score corresponds to more frailty.21 Although albumin is considered a component of the ADL score, this information was unfortunately not available for our cohort. 

The unadjusted and adjusted effects of age on follow-up KCCQ-OS were also assessed using linear regression modeling, with age as a continuous variable. The adjusted model included baseline STS-PROM score, baseline KCCQ-OS score, and frailty score. All analyses were performed using SPSS software (Statistics for Mac, version 25.0, released 2017; IBM Corporation). All tests were two sided, and a P-value of ≤.05 was considered significant.

Results

Between January 1, 2015 and December 31, 2018, a total of 223 patients underwent TAVR at our center. Baseline and follow-up KCCQ data were available for 218 patients. Mean age for the overall cohort was 83.9 ± 6.4, 52.9% were men, 26.9% had diabetes, and mean STS-PROM score was 5.1 ± 2.8 (Table 1). Overall, nonagenarians had significantly lower body mass indexes, were less often diabetic, and had better handgrip strength. Rates of congestive heart failure and chronic kidney disease were numerically lower in the nonagenarians; however, this did not meet statistical significance. There was no significant difference in the frailty score between the two groups. There was one intraprocedural death in the nonagenarian group. There was no significant difference in follow-up mortality between the two groups. 

Baseline and 30-day follow-up mean KCCQ-OS of the two groups were similar (baseline, 50.07 ± 17.08 vs 51.08 ± 18.41 [P=.70]; 30-day follow-up, 73.91 ± 12.99 vs 81.24 ± 15.20 [P=.70] in the nonagenarian group vs the younger group, respectively) (Figure 1). Although there was a significant increase in the 30-day KCCQ-OS score in both age groups (P<.001), there was a significant effect of age on 30-day KCCQ-OS after controlling for baseline KCCQ-OS, frailty, and STS-PROM (F[1-217]=7.412; P<.01). Nonagenarians had an average of 6.45 points lower in their 30-day KCCQ-OS scores than younger patients in the adjusted analysis (Figure 2).

Similar findings of more improvement in the younger group were noted in adjusted analysis with most of the KCCQ subscales: PL component, which describes limitations on routine activities (KCCQ-PL, F[1]=8.42; P<.01); SL component, which describes participation in daily activities and chores (KCCQ-SL, F[1]=4.08; P=.04), and SF component, which quantifies the frequency of heart failure symptoms, such as shortness of breath, fatigue, and lower-extremity edema (KCCQ-SF, F[1]=4.61; P=.03). No statistically significant difference, however, was noted in the QoL component (KCCQ-QL, F[1]=2.52; P=.11) (Table 2). 

Discussion

There has been an increase in TAVR therapy over the past decade, with pivotal trials demonstrating non-inferiority of this therapy compared with surgical aortic valve replacement.4,22,23 Although nonagenarians did not constitute a large part of the pivotal TAVR trials, they do constitute a growing population of patients (16%) undergoing TAVR commercially.14 It is thus important to not only understand major clinical outcomes in this population, but also the health status benefits of this procedure in nonagenarians.

In this single-center adjusted analysis of patients undergoing TAVR, we demonstrated that nonagenarians had a significant improvement in QoL. Nonagenarians represent a more select group of patients compared with their younger counterparts. They were more likely to be female, less likely to have comorbid conditions, such as obesity, diabetes, hypertension, congestive heart failure, and chronic kidney disease, and had an overall higher ejection fraction. These findings are in line with previous studies.14 Unique to this study, we also examined frailty variables in our population. Similar findings were noted; nonagenarians had a higher grip strength, and were on par with their counterparts in terms of walking and activities of daily living.

However, despite the more favorable baseline characteristics, the younger group (<90 years old) had greater improvement in the measured QoL outcomes compared with the nonagenarians in the adjusted analysis that accounted for both STS score and frailty. This finding only demonstrates that there is a reduction in the attainable QoL with advancing age, as shown with the linear regression analysis. Nonetheless, the improvement noted in the KCCQ-OS  score in the nonagenarians (23.8 ± 15.64 points) corresponds to a large and substantial clinical improvement in QoL in these patients.20 Furthermore, improvement was noted across all the domains, demonstrating significant improvements in both physical and social limitations. Overall improvement in KCCQ was similar to previous studies.14,24,25

No significant difference was noted in the perioperative and 30-day mortality rates, which was likely due to better patient selection and safer procedural techniques. Similar to findings from previous studies,14,15,26 however, the low number of patients in this study limits our interpretation of this finding. 

Despite approval of TAVR across all risk strata, there remains hesitation to refer patients of “extreme” age. Referral rates remain low, even in areas with TAVR availability.27 Our findings indicate that with careful patient selection, TAVR may provide a substantial clinical improvement in QoL regardless of age. 

Study limitations. There are several limitations to this study. The small sample study limits generalizability, and also limits interpretation of the mortality data. No data were available on stroke, vascular/bleeding complications, or other procedural complications. The retrospective nature of the analysis also has inherent limitations. 

Conclusion

Our data suggest a significant clinical improvement with TAVR in nonagenarians.


From 1Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida; 2Tenet Healthcare Corporation, Boca Raton, Florida; 3 Department of Cardiovascular Diseases, Florida Atlantic University, Boca Raton, Florida; and 4Department of Internal Medicine, Florida Atlantic University, Boca Raton, Florida.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript accepted February 4, 2020.

Address for correspondence: Brijeshwar Maini, MD, Tenet Florida, Boca Raton, FL 33431. Email: brijmaini1@gmail.com

References
  1. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374:1609-1620.
  2. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380:1695-1705.
  3. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70:252-289.
  4. Leon MB, Smith CR, Mack MJ, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597-1607.
  5. Reynolds MR, Magnuson EA, Lei Y, et al. Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis. Circulation. 2011;124:1964-1972.
  6. Moat NE, Ludman P, de Belder MA, et al. Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry. J Am Coll Cardiol. 2011;58:2130-2138.
  7. Thomas M, Schymik G, Walther T, et al. One-year outcomes of cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry: the European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve. Circulation. 2011;124:425-433.
  8. Gilard M, Eltchaninoff H, lung B, et al. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med. 2012;366:1705-1715.
  9. Bonow RO, Greenland P. Population-wide trends in aortic stenosis incidence and outcomes. Circulation. 2015;131:969-971.
  10. Noble S, Frangos E, Samaras N, et al. Transcatheter aortic valve implantation in nonagenarians: effective and safe. Eur J Intern Med. 2013;24:750-755.
  11. Mack MC, Szerlip M, Herbert MA, et al. Outcomes of treatment of nonagenarians with severe aortic stenosis. Ann Thorac Surg. 2015;100:74-80.
  12. Akin I, Kische S, Paranskaya L, et al. Morbidity and mortality of nonagenarians undergoing CoreValve implantation. BMC Cardiovasc Disord. 2012;12:80.
  13. Yamamoto M, Meguro K, Mouillet G, et al. Comparison of effectiveness and safety of transcatheter aortic valve implantation in patients aged ≥90 years versus <90 years. Am J Cardiol. 2012;110:1156-1163.
  14. Arsalan M, Szerlip M, Vemulapalli S, et al. Should transcatheter aortic valve replacement be performed in nonagenarians?: insights from the STS/ACC TVT registry. J Am Coll Cardiol. 2016;67:1387-1395.
  15. Thourani VH, Jensen HA, Babaliaros V, et al. Outcomes in nonagenarians undergoing transcatheter aortic valve replacement in the PARTNER-I Trial. Ann Thorac Surg. 2015;100:785-792.
  16. Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000;35:1245-1255.
  17. Pettersen KI, Reikvam A, Rollag A, Stavem K. Reliability and validity of the Kansas City Cardiomyopathy Questionnaire in patients with previous myocardial infarction. Eur J Heart Fail. 2005;7:235-242.
  18. Spertus JA, Jones PG. Development and validation of a short version of the Kansas City Cardiomyopathy Questionnaire. Circ Cardiovasc Qual Outcomes. 2015;8:469-476.
  19. Spertus JA. The Kansas City Cardiomyopathy Questionnaire (KCCQ). 2004.
  20. Spertus JA, Peterson E, Conard MW, et al. Monitoring clinical changes in patients with heart failure: a comparison of methods. Am Heart J. 2005;50:707-715.
  21. Afilalo J, Alexander KP, Mack MJ, et al. Frailty assessment in the cardiovascular care of older adults. J Am Coll Cardiol. 2014;63:747-762.
  22. Chen S, Redfors B, Ben-Yehuda O, et al. Transcatheter versus surgical aortic valve replacement in patients with prior cardiac surgery in the randomized PARTNER 2A trial. JACC Cardiovasc Interv. 2018;11:2207-2216.
  23. Frerker C, Baldus S, Nitschmann S. Transcatheter aortic valve replacement: PARTNER 3 trial and Evolut low risk trial. Internist (Berl). 2019;60:1221-1224.
  24. Arnold SV, Afilalo J, Spertus JA, et al. Prediction of poor outcome after transcatheter aortic valve replacement. J Am Coll Cardiol. 2016;68:1868-1877.
  25. Thourani VH, Suri RM, Gunter RL, et al. Contemporary real-world outcomes of surgical aortic valve replacement in 141,905 low-risk, intermediate-risk, and high-risk patients. Ann Thorac Surg. 2015;99:55-61.
  26. Vlastra W, Chandrasekhar J, Vendrik J, et al. Transfemoral TAVR in nonagenarians: from the CENTER Collaboration. JACC Cardiovasc Interv. 2019;12:911-920.
  27. Ielasi A, Latib A, Tespili M, Donatelli F. Current results and remaining challenges of transcatheter aortic valve replacement expansion in intermediate and low risk patients. Int J Cardiol Heart Vasc. 2019;23:100375.
/sites/invasivecardiology.com/files/articles/images/375-379%20Khalili%20JIC%202020%20Oct%20wm.pdf