- Email: [email protected]
Usefulness of Balloon Aortic Valvuloplasty in the Management of Patients With Aortic Stenosis
Usefulness of Balloon Aortic Valvuloplasty in the Management of Patients With Aortic Stenosis Molly Szerlip, MDa, Mani Arsalan, MDb,c, Molly C. Mack, BAb, Giovanni Filardo, PhD, MPHb, Christina Worley, RNb, Rebeca J. Kim, BAb, Teresa Phan, MSb, Benjamin Pollock, MSb, Cynthia Rangel, BAb, David L. Brown, MDa, Michael Mack, MDd, and Elizabeth M. Holper, MD, MPHa,* We aim to evaluate the contemporary role and outcomes of balloon aortic valvuloplasty (BAV), based on physician intent, for the management of severe aortic stenosis. This is a prospective, 2-center study of 100 consecutive high-risk patients with severe aortic stenosis who underwent BAV. Before BAV, physicians assigned intent as (1) bridge to decision (BTD); (2) therapeutic bridge to planned therapy; or (3) palliation. Patients in the BTD arm underwent clinical assessment at 30 days to determine eligibility for definitive valve therapy. All patients were followed up to 1 year, with outcomes measured including procedural complications, Kansas City Cardiomyopathy Questionnaires scores, 30-day and 1-year mortality, and definitive valve therapy. Enrolled patients had a mean age of 80.6 (±9.6) years, Society of Thoracic Surgeons predicted risk of mortality of 11.4% (±7.1%), and 91 (91.0%) patients had class III or IV New York Heart Association congestive heart failure. Intent in the 100 study patients was 76 BTD; 20 therapeutic bridge to planned therapy; and 4 palliation. Thirty-day mortality for all patients was 6 of 100 (6.0%), and 1-year mortality for all patients who received definitive valve therapy was 6 of 54 (11.1%). For patients surviving to 30 days, adjusted (by Society of Thoracic Surgeons predicted risk of mortality) Kansas City Cardiomyopathy Questionnaires scores were significantly improved from baseline for all patients and BTD patients. In conclusion, as a bridge to decision and treatment tool, BAV appears to have a valuable role in properly selecting and improving patients to undergo definitive valve replacement. © 2017 Elsevier Inc. All rights reserved. (Am J Cardiol 2017;120:1366–1372) Balloon aortic valvuloplasty (BAV) for the management of patients with severe aortic stenosis (AS), first reported in 1986 by Cribier, was proposed as an “alternative treatment whenever surgical valve replacement proved impracticable.”1 The initial enthusiasm for BAV was attenuated by studies demonstrating high complication rates leading to increased morbidity and mortality.2 Furthermore, with a high recurrence rate of AS, long-term survival rate was not improved by BAV, but it remained the only management option for symptomatic inoperable patients.3,4 BAV has also been performed in patients before urgent noncardiac surgery and as a therapeutic bridge to surgical aortic valve replacement (SAVR). In recent decades, the complication rate of BAV has been reduced by careful patient selection and technical improvements.5 Interest in the role of BAV has been renewed a Interventional Cardiology, The Heart Hospital Baylor Plano, Plano, Texas; b Cardiovascular Research, Baylor Research Institute, Dallas, Texas; cCardiothoracic Surgery, Kerckhoff-Klinik, Bad-Nauheim, Germany; and dCardiac Surgery, The Heart Hospital Baylor Plano, Plano, Texas. Manuscript received March 12, 2017; revised manuscript received and accepted July 3, 2017. MM serves as an uncompensated member of the Executive Committee of the PARTNER Trial; the remaining authors have no disclosures relevant to this manuscript. See page 1372 for disclosure information. *Corresponding author: Tel: (469) 814-4720; fax: (469) 814-3999. E-mail address: [email protected] (E.M. Holper).
0002-9149/© 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2017.07.024
with the introduction of transcatheter aortic valve implantation (TAVI). Since the first clinical use in 2002, TAVI has emerged to be the preferred treatment in inoperable and high surgical risk patients, and has become a component of some TAVI procedures to facilitate successful valve implantation.6,7 Due to the introduction of TAVI, the role of BAV in the management of patients with severe AS has changed. This is the first prospective study to investigate the contemporary role and outcomes of BAV in the TAVI era. Methods This is a prospective, 2-center study of 100 high-risk patients undergoing BAV for management of severe AS. Patients were enrolled in the study from July 2013 through June 2014. Before the procedure, physicians assigned the intent of performing BAV as (1) a bridge to decision whether to treat (BTD); (2) therapeutic bridge to planned therapy (BTX) to improve candidacy; or (3) palliation only (PAL). This designation was derived by consideration of patient demographics, current clinical status, as well as frailty parameters. All patients underwent clinical assessment at 30 days to determine eligibility for definitive valve therapy and functional outcomes. Baseline demographics were recorded as per the Society of Thoracic Surgeons (STS) definitions. Frailty was assessed using serum albumin, gait speed, Katz activities of daily living score, and grip strength.8 All patients were followed up to 1 year, with outcomes measured including www.ajconline.org
Valvular Heart Disease/Prospective Study of BAV
procedural complications, 30-day and 1-year mortality, and definitive valve therapy by SAVR or TAVI. Quality of life (QoL) was measured by the Kansas City Cardiomyopathy Questionnaires (KCCQ), using the 12-question short form.9 All patients underwent individual informed consent for the study, and the study was approved by the Institutional Review Board at both hospitals. Patient demographic data were tabulated according to the indication for BAV: (1) BTD; (2) BTX; or (3) Palliation (PAL). Unadjusted chi-square tests for categorical variables and Wilcoxon rank-sum tests for continuous variables were used to compare baseline demographics between BTD versus BTX. The PAL group (n = 4) was not considered in the statistical comparisons due to the low sample size. A Bonferroni correction was used to correct for multiplicity in baseline comparisons. The mean differences in aortic valve area (AVA) pre- and post-BAV were compared within each BAV indication using unadjusted paired t tests. Kaplan-Meier curves were generated to depict unadjusted 1-year survival rate for the BTD and BTX groups. Additionally, a Cox model adjusted for the STS predicted risk of mortality10 (modeled with a 5-knot restricted cubic spline),11,12 and valve therapy (yes/no) was used to estimate survival rate for BTD and BTX patients. Unadjusted means and standard deviations for patient KCCQ summary scores were reported by study period (baseline, 30 days, 3 months, 6 months, and 1 year). To assess the impact of BAV on QoL 30 days after procedure, a general linear model accounting for patients’ repeated measures was developed. The KCCQ summary score (baseline and 30day) was the model outcome, and the STS predicted risk of mortality and an indicator variable for the baseline KCCQ score (vs 30-day) were the independent variables. This analysis was repeated for the subgroups of BTD and BTX patients. Two of the patients in the BTD and BTX cohorts were missing baseline KCCQ scores and were thus not included in the analysis. Due to the small sample, the impact of BAV on 30-day QoL for the PAL group was assessed using the general linear model with 1 independent variable only: the indicator variable for the baseline KCCQ score (vs 30 days). BAV was performed by a standard technique using Tyshak II, Z-Med, and Z-Med X balloons (B. Braun Medical Inc., Bethlehem, Pennsylvania) ranging from 22 to 30 mm in diameter based on aortic annular size by transthoracic echocardiogram or computed tomography. Peak and mean aortic valve gradients and thermodilution cardiac outputs were recorded. The AVA was calculated using the continuity equation. Serial inflations were performed during rapid ventricular pacing (180 to 200 beats/min), which continued until the balloon was deflated. Valvuloplasty was considered complete when the largest diameter balloon appropriate for the patient’s annular size was utilized and/or a 50% decrease in mean aortic valve gradient was measured. At the end of the procedure, peak and mean gradients were recorded and AVA calculated.
1367
York Heart Association (NYHA) congestive heart failure (Table 1). No significant differences in baseline demographics were observed in the study population when comparing the BTD and BTX groups, except peripheral vascular disease was more common in the BTX group (60.0% vs 25.0%, p = 0.05). A 4-point frailty evaluation was performed in all patients, with 37% and 5% of patients in the BTD and BTX groups, respectively, failing 2 out of 4 of these tests. The types of transcatheter valves used in the 47 patients who underwent TAVI included the following: Sapien (n = 13), Sapien XT (n = 9), Sapien 3 (n = 14), unknown Sapien valve (placed out of state, n = 1); and CoreValve (n = 10). Intention and treatment outcomes in the 100 patients enrolled are shown in Figure 1: 76 BTD; 20 BTX; and 4 PAL. At 30 days, all 3 study groups obtained significant increases in AVA measured by echocardiogram compared with baseline (Table 2). A 30-day mortality for all patients was 6 of 100 (6.0%). One of these patients was in the PAL cohort and 5 were in the BTD cohort and not referred for definitive valve therapy. There was no procedural mortality in patients who underwent TAVI or SAVR. Other complications after BAV included cerebrovascular event in 2 of 100 (2.0%) and acute kidney injury in 2 of 100 (2.0%). The majority of patients in the BTD and BTX groups were discharged to home after BAV (71.1% and 80.0%, respectively). Overall 1-year mortality for the study was 41 of 100 patients (41.0%). In BTD patients, mortality at 1 year was 33 of 76 (43.4%), whereas in BTX patients 1-year mortality was 5 of 20 (25.0%). One-year mortality in the PAL group was 3 of 4 (75.0%). When all patients who received definitive valve therapy are considered, the 1-year mortality was 6 of 54 (11.1%). In the BTD group, 5 of the patients died within 1 year (4 TAVI and 1 SAVR), and these deaths occurred at 33, 54, 206, 282, and 302 days after procedure. In the BTX group, 1 patient who underwent SAVR died within 1 year, and this death occurred at 105 days after procedure. Patients who did not receive definitive valve therapy (excluding the PAL patients) experienced 1-year mortality in 32 of 42 cases (76.2%) (Figure 2). Patients in the BTD arm who received definitive valve therapy had a 1-year mortality of 13.2% (5 of 38) and in the BTX arm had a 1-year mortality of 6.3% (1 of 16). The majority of patients in this study who underwent definitive valve therapy were referred for TAVI (33 of 38 in BTD and 14 of 16 in BTX); with the remainder receiving SAVR. The adjusted analysis of KCCQ summary scores showed that overall 30-day KCCQ scores were significantly improved from baseline (Figure 3), although only the BTD patients showed significant KCCQ summary scores at 30 days in the subgroup analysis. An evaluation of the unadjusted KCCQ scores at each time point demonstrates the largest increase from 30 days to 3 months, likely related to referral for definitive valve therapy with similar values at 6 months and 1 year (Table 3). Further statistical analysis was not done with the later KCCQ values given the primary influence of definitive valve therapy on the change and not effects of the BAV procedure.
Results The patients had a mean (±standard deviation) age of 80.6 (±9.6) years, mean STS predicted risk of mortality of 11.4% (±7.1%), and 91 (91.0%) patients were class III or IV New
Discussion Early studies reported BAV procedural success rates between 80% and 90%; however, the procedure was associated
1368
The American Journal of Cardiology (www.ajconline.org)
Table 1 Patient demographic characteristic by balloon aortic valvuloplasty indication Preoperative Characteristic: Age (years) Women White Black Other Body mass index (kg/m2) Diabetes mellitus End Stage Renal Disease Hypertension Failed 2/4 Frailty Tests Hand Grip Strength Katz Activities of Daily Living 5 meter walk time (minutes) Serum albumin Severe Liver Disease Coronary artery disease Peripheral vascular disease Cerebrovascular disease Cerebrovascular accident Myocardial infarction Ejection fraction NYHA Class I II III IV Prior coronary bypass Prior valve surgery STS predicted risk of mortality
Bridge to Decision (BTD) (n = 76)
Bridge to Therapy (BTX) (n = 20)
p-Value*
Palliation (n = 4)
80.0 ± 9.9 48.7%
82.2 ± 6.1 40.0%
>0.99 >0.99 >0.99
83.5 ± 19.4 50.0%
85.5% 5.3% 9.2% 28.6 ± 10.5 39.5% 5.5% 86.8% 37.0% 17.9 ± 9.7 4.7 ± 1.6 8.7 ± 7.0 3.2 ± 0.4 2.7% 63.2% 25.0% 26.3% 15.8% 21.1% 42.1 ± 16.8%
95.0% 0.0% 5.0% 28.2 ± 6.2 40.0% 5.0% 85.0% 5.0% 18.6 ± 10.6 5.2 ± 1.1 8.2 ± 5.8 3.4 ± 0.5 0.0% 50.0% 60.0% 40.0% 10.0% 20.0% 50.3 ± 10.9%
0.0% 5.3% 17.1% 77.6% 32.9% 0.0% 11.6 ± 6.9
5.0% 5.0% 20.0% 70.0% 20.0% 5.0% 10.3 ± 6.1
>0.99 >0.99 >0.99 >0.99 0.10 >0.99 >0.99 >0.99 >0.99 >0.99 >0.99 0.05 >0.99 >0.99 >0.99 0.25 >0.99
>0.99 0.85 >0.99
100.0% 0.0% 0.0% 27.2 ± 12.5 50.0% 0.0% 100.0% — 16.0 ± 2.8 6.0 ± 0.0 6.5 ± 1.1 3.5 ± 0.5 — 25.0% 25.0% 25.0% 25.0% 0.0% 55.0 ± 21.6% 0.0% 25.0% 25.0% 75.0% 25.0% 0.0% 16.6 ± 10.0
NYHA = New York Heart Association; STS = Society of Thoracic Surgery. * Un-adjusted p-value comparing BTD versus BTX with Bonferroni correction for multiplicity.
with complication rates up to 30% and mortality up to 14%.2,13 More recent data from Eltchaninoff and colleagues reported a major complication rate of 6.8% and an in-hospital mortality rate of 2.5%, with a procedural success rate of 81%.14 These studies, however, are limited by lack of knowledge regarding intent or clinical goals of the BAV procedure. We, therefore, performed this prospective study to evaluate contemporary indications and outcomes by assigned intent before the BAV procedure. In our study, we report significantly increased AVA with low complication rates in a high-risk population of AS patients undergoing BAV. Next, we discuss the role of BAV for PAL, BTD, and BTX in the treatment of AS. In our study we employed BAV for palliation in only 4 patients, with a 75% mortality rate at 1 year. Data from the outcome of patients in the Placement of AoRtic TraNscathetER valves (PARTNER) trial who were unsuitable for SAVR and TAVI and underwent BAV demonstrated, like our study, a high mortality rate of BAV, if AVR is not performed at a later time.15 Although, Kapadia et al did detect an increased survival rate at 3 months in patients undergoing BAV, this difference was not sustained after 6 months. Due to the small sample size of PAL patients in our study, we cannot make any specific conclusions, with larger trials needed to prove that BAV still has a place in the armamentarium of PAL care.
The 2017 American College of Cardiology/American Heart Association guidelines recommend BAV as a bridge to SAVR or TAVI in patients with severe symptomatic AS (class IIB, level of evidence C).16 In our study, BAV as a BTX therapy was performed in 20 patients already considered candidates for definitive valve therapy and in 76 patients, BAV was performed as a bridge to decision. Other studies have demonstrated the clinical benefit of BAV in this bridging role. Doguet and colleagues showed that BAV could reduce the operative risk score in inoperable patients.17 Kefer and colleagues18 reported BAV resulted in an improved ejection fraction (EF) and decreased brain natriuretic peptide (BNP) plasma level in 22 of 59 (37%) patients with reduced EF (EF <40), with symptomatic improvement and increased 1-year survival rate. Kapadia et al demonstrated that bridging to SAVR with BAV (median time between procedures of 78 days) resulted in acceptable 1-year survival rate (78%).19 TAVI increases the spectrum of patients who are suitable for valve therapy, but outcomes of definitive valve therapy after BAV are not well described. We report a 1-year survival rate of 48 of 54 (88.9%) in patients undergoing definitive valve therapy after BAV as a bridge. There are several ways to explain this high survival rate in our study patients compared with previous reports. One is that BAV is able to successfully bridge patients to definitive valve therapy by optimizing clinical status,
Valvular Heart Disease/Prospective Study of BAV
1369
Figure 1. Assigned intent for BAV and treatment outcomes. BAV = balloon aortic valvuloplasty; SAVR = surgical aortic valve replacement; TAVR = transcatheter aortic valve replacement.
Figure 2. STS risk-adjusted survival curves for BTX and BTD patients by definitive valve therapy adjusted for STS predicted risk of mortality. BTD = bridge to decision; BTX = bridge to therapy; STS = Society of Thoracic Surgeons.
1370
The American Journal of Cardiology (www.ajconline.org)
Table 2 Patient outcomes by balloon aortic valvuloplasty indication
Intraprocedural Outcomes: Mean relative decrease in mean gradient post BAV >50% relative decrease in gradient post BAV Received definitive valve therapy No definitive valve therapy 30-day outcomes: Mean change (cm2) in Aortic Valve Area 30-day mortality Acute Kidney Injury Vascular complications Major Minor Neurological complication Stroke TIA Bleeding Minor Major Length of stay (days) Discharge location Home Long-term Care/Nursing Home/Rehab Other hospital/death Other outcomes: Received definitive valve therapy Days from BAV to valve therapy mean ± SD median (min, max) 1-year mortality
Bridge to Decision (BTD) (n = 73)
Bridge to Therapy (BTX) (n = 19)
Palliation (n = 3)
45.7% (41.2%–50.2%)† 29/73 (39.7%) 14/29 (48.3%) 15/29 (51.7%) (n = 76) +0.31 (0.17–0.45)* 5 (6.6%) 1 (1.3%)
38.0% (30.7%–45.4%)† 5/19 (26.3%) 4/5 (80.0%) 1/5 (20.0%) (n = 20) +0.20 (0.16–0.25)* 0 (0.0%) 1 (5.0%)
50.1% (36.9%–63.2%) 2/3 (66.7%) 0/2 (0%) 2/2 (100.0%) (n = 4) +0.22 (0.03–0.41)* 1 (25.0%) 0 (0.0%)
2 (2.6%) 0 (0.0%)
1 (5.0%) 0 (0.0%)
0 (0.0%) 1 (25.0%)
1 (1.3%) 1 (1.3%)
0 (0.0%) 0 (0.0%)
0 (0.0%) 0 (0.0%)
3 (3.9%) 3 (3.9%) 4.0 ± 4.9
1 (5.0%) 0 (0.0%) 4.1 ± 5.4
0 (0.0%) 0 (0.0%) 3.0 ± 6.0
54 (71.1%) 16 (21.1%) 6 (7.8%)
16 (80.0%) 4 (20.0%) 0 (0.0%)
2 (50.0%) 1 (25.0%) 1 (25.0%)
38 (50.0%)
16 (80.0%)
0 (0.0%)
93 ± 77 64 (19, 307) 33 (43.4%)
48 ± 27 36 (11, 106) 5 (25.0%)
— — 3 (75.0%)
BAV = balloon aortic valvuloplasty; TIA = transient ischemic attack. * Unadjusted paired t-test comparing post-BAV Aortic Valve Area versus pre-BAV Aortic Valve Area (with 95% Confidence Intervals). † Unadjusted paired t-test comparing post-BAV mean gradient versus pre-BAV mean gradient (with 95% Confidence Intervals).
often the presence of congestive heart failure. Secondly, BAV may allow the ability to differentiate those patients with clinical improvement to optimally select appropriate patients for valve therapy. Lastly, this finding may be explained by patient survival rate bias, as the patients undergoing definitive treatment must initially benefit from BAV and survive long enough to receive further therapy. The reevaluation of patients after BAV in the BTX group resulted in 4 patients initially referred for definitive therapy to subsequently not undergo the planned therapy. One patient had severe peripheral arterial disease and underwent below the knee arterial revascularization at the time of BAV due to a nonhealing ulcer. While waiting for wound healing, the patient died 109 days after the BAV. The second patient had significant clinical improvement after BAV and did not wish to pursue TAVI, but was admitted with congestive heart failure (CHF) and died 198 days post-BAV. The third patient had chronic renal insufficiency and was admitted with acute onchronic renal insufficiency and hypotension 11 days after BAV, which progressed, and led to death 35 days later. The fourth patient was admitted 22 days after BAV with a non-ST segment elevation myocardial infarction and underwent coronary stenting, complicated by postprocedure cardiogenic shock, multisystem organ failure, cardiac arrest, and death 33 days after BAV. Of these 4 patients, the third patient’s course appears
directly related to BAV complications, the fourth patient is possibly related, and the first 2 are not related to BAV complications. For patients in the BTD group who were not felt to be TAVI or SAVR candidates after BAV, the 1-year mortality of 28 of 38 (73.7%) was even higher than historical mortality rates of medically treated patients with AS.20,21 This is likely due not only to the high-risk level of our study patients, but also points to the importance of withholding invasive and costly technology in patients who may not meet clinical criteria to realize long-term benefit. It is important to note that this study was not designed to compare the outcomes of the BTD and BTX groups, given the different populations of patients at baseline. Additionally, comparison regarding the outcomes of no definitive valve therapy versus definitive valve therapy after BAV was not the outcome of interest in this study. Lastly, in the BTD and BTX groups; only approximately 40% and 26%, respectively, had postprocedure reduction of at least 50% in the aortic valve gradient. However, the protocol required either maximum size BAV balloon as measured by preprocedure imaging or >50% gradient reduction, which are the common clinical criteria utilized. This report demonstrates the ability of BAV to improve short-term QoL in high-risk patients with AS. Especially in
Valvular Heart Disease/Prospective Study of BAV
1371
Figure 3. Unadjusted and STS risk-adjusted baseline and 40-day KCCQ summary scores by BAV indication with 95% confidence intervals. Adjusted for baseline KCCQ score and STS predicted risk of mortality and accounting for patients’ repeated measures. BAV = balloon aortic valvuloplasty; BTD = bridge to decision; BTX = bridge to therapy; KCCQ = Kansas City Cardiomyopathy Questionnaire; STS = Society of Thoracic Surgeons.
Table 3 Patient Kansas City Cardiomyopathy Questionnaire scores throughout study period Study Period: Unadjusted: Baseline KCCQ summary score 30-day KCCQ summary score 3-month KCCQ summary score 6-month KCCQ summary score 1-year KCCQ summary score Adjusted: All patients Baseline KCCQ summary score 30-day KCCQ summary score Bridge to decision patients Baseline KCCQ summary score 30-day KCCQ summary score‡ Bridge to therapy patients Baseline KCCQ summary score 30-day KCCQ summary score§ Palliative patients Baseline KCCQ summary score 30-day KCCQ summary score
n*
Mean ± SD
n = 94 n = 76 n = 35 n = 22 n=7
34.9 ± 22.0 45.2 ± 27.7 59.3 ± 30.2 60.4 ± 28.8 68.6 ± 37.5 Mean (95% CI)
n = 94 n = 76
33.1 (28.4–37.8) 43.5 (38.3–48.6)
<0.0001
n = 73 n = 57
33.3 (28.3–38.2) 45.1 (39.0–51.1)
0.001
n = 17 n = 12
38.8 (29.5–48.2) 44.6 (12.5–95.1)
0.224
n=4 n=3
49.4 (25.1–73.7) 56.0 (26.4–100)
0.825‖
BAV = balloon aortic valvuloplasty; KCCQ = Kansas City Cardiomyopathy Questionnaire. * n represents number of fully completed KCCQ summary scores at each study period. † Adjusted for baseline KCCQ score and STS predicted risk of mortality and accounting for patients’ repeated measures. ‡ n = 2 bridge to decision patients with 30-day KCCQ were missing baseline KCCQ. § n = 2 bridge to therapy patients with 30-day KCCQ were missing baseline KCCQ. ‖ Unadjusted due to sample size.
p-Value† Not estimated given the primary influence of definitive valve therapy on the change and not effects of the BAV procedure.
1372
The American Journal of Cardiology (www.ajconline.org)
an elderly population, survival rate with a meaningful functional outcome and QoL is paramount. Several studies have shown an improvement of QoL after BAV and TAVI with a stabilization of KCCQ after 6 months.15,22,23 Similar to our findings, Kapadia and colleagues showed an improvement of more than 10 points in the KCCQ overall summary scale at 30 days in patients undergoing BAV in the PARTNER trial.24 We confirm the beneficial impact of BAV on QoL in clinical practice. Even in patients who are not eligible for TAVI, a discussion of the procedural risks versus benefits in terms of QoL may be warranted. The contemporary role of BAV is as an effective tool to optimize the clinical status of selected patients for definitive therapy as well as an effective decision-making tool. We demonstrate in this study a high success rate and low complication rate of BAV in such a role. Additionally, QoL is improved at 30 days with BAV. In summary, BAV is shown to be an effective decision-making tool for patient selection, leading to excellent 1-year survival rate if TAVI or SAVR are performed subsequently.
9. 10.
11. 12. 13. 14.
15.
Acknowledgment: We would like to thank John J. Squiers, BSE, for his editorial support during preparation of this report. Disclosures The authors have no conflicts of interest to disclose. 1. Cribier A, Savin T, Saoudi N, Rocha P, Berland J, Letac B. Percutaneous transluminal valvuloplasty of acquired aortic stenosis in elderly patients: an alternative to valve replacement? Lancet 1986;1:63–67. 2. Percutaneous balloon aortic valvuloplasty. Acute and 30-day followup results in 674 patients from the NHLBI Balloon Valvuloplasty Registry. Circulation 1991;84:2383–2397. 3. Lieberman EB, Bashore TM, Hermiller JB, Wilson JS, Pieper KS, Keeler GP, Pierce CH, Kisslo KB, Harrison JK, Davidson CJ. Balloon aortic valvuloplasty in adults: failure of procedure to improve long-term survival. J Am Coll Cardiol 1995;26:1522–1528. 4. Letac B, Cribier A, Koning R, Bellefleur JP. Results of percutaneous transluminal valvuloplasty in 218 adults with valvular aortic stenosis. Am J Cardiol 1988;62:598–605. 5. Ben-Dor I, Pichard AD, Satler LF, Goldstein SA, Syed AI, Gaglia MA Jr, Weissman G, Maluenda G, Gonzalez MA, Wakabayashi K, Collins SD, Torguson R, Okubagzi P, Xue Z, Kent KM, Lindsay J, Waksman R. Complications and outcome of balloon aortic valvuloplasty in high-risk or inoperable patients. JACC Cardiovasc Interv 2010;3:1150–1156. 6. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Lung B, Lancellotti P, Pierard L, Price S, Schafers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M, ESC Committee for Practice Guidelines (CPG), Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42:S1–S44. 7. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD, American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438–2488. 8. Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA, Popma JJ, Ferrucci L, Forman DE. Frailty assessment in the cardio-
16.
17.
18.
19.
20. 21. 22.
23.
24.
vascular care of older adults. J Am Coll Cardiol 2014;63:747– 762. 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. O’Brien SM, Shahian DM, Filardo G, Ferraris VA, Haan CK, Rich JB, Normand SL, DeLong ER, Shewan CM, Dokholyan RS, Peterson ED, Edwards FH, Anderson RP, Society of Thoracic Surgeons Quality Measurement Task Force. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2—isolated valve surgery. Ann Thorac Surg 2009;88:S23–S42. Filardo G, Hamilton C, Hamman B, Ng HK, Grayburn P. Categorizing BMI may lead to biased results in studies investigating in-hospital mortality after isolated CABG. J Clin Epidemiol 2007;60:1132–1139. Harrell F Jr. Regression modeling strategies: with application to linear models, logistic regression, and survival analysis. New York: SpringerVerlag; 2001. McKay RG. The Mansfield Scientific Aortic Valvuloplasty Registry: overview of acute hemodynamic results and procedural complications. J Am Coll Cardiol 1991;17:485–491. Eltchaninoff H, Durand E, Borz B, Furuta A, Bejar K, Canville A, Farhat A, Fraccaro C, Godin M, Tron C, Sakhuja R, Cribier A. Balloon aortic valvuloplasty in the era of transcatheter aortic valve replacement: acute and long-term outcomes. Am Heart J 2014;167:235–240. Kapadia S, Stewart WJ, Anderson WN, Babaliaros V, Feldman T, Cohen DJ, Douglas PS, Makkar RR, Svensson LG, Webb JG, Wong SC, Brown DL, Miller DC, Moses JW, Smith CR, Leon MB, Tuzcu EM. Outcomes of inoperable symptomatic aortic stenosis patients not undergoing aortic valve replacement: insight into the impact of balloon aortic valvuloplasty from the PARTNER trial (Placement of AoRtic TraNscathetER Valve trial). JACC Cardiovasc Interv 2015;8:324–333. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O’Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A. 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. doi:10.1016/j.jacc.2017.03.011. Doguet F, Godin M, Lebreton G, Eltchaninoff H, Cribier A, Bessou JP, Litzler PY. Aortic valve replacement after percutaneous valvuloplasty— an approach in otherwise inoperable patients. Eur J Cardiothorac Surg 2010;38:394–399. Kefer J, Gapira JM, Pierrard S, DeMeester C, Gurne O, Chenu P, Renkin J. Recovery after balloon aortic valvuloplasty in patients with aortic stenosis and impaired left ventricular function: predictors and prognostic implications. J Invasive Cardiol 2013;25:235–241. Kapadia SR, Goel SS, Yuksel U, Agarwal S, Pettersson G, Svensson LG, Smedira NG, Whitlow PL, Lytle BW, Tuzcu EM. Lessons learned from balloon aortic valvuloplasty experience from the pre-transcatheter aortic valve implantation era. J Interv Cardiol 2010;23:499–508. Schwarz F, Baumann P, Manthey J, Hoffmann M, Schuler G, Mehmel HC, Schmitz W, Kubler W. The effect of aortic valve replacement on survival. Circulation 1982;66:1105–1110. Ross J Jr, Braunwald E. Aortic stenosis. Circulation 1968;38:61–67. Arnold SV, Reynolds MR, Wang K, Magnuson EA, Baron SJ, Chinnakondepalli KM, Reardon MJ, Tadros PN, Zorn GL, Maini B, Mumtaz MA, Brown JM, Kipperman RM, Adams DH, Popma JJ, Cohen DJ, CoreValve US Pivotal Trial Investigators. Health status after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis at increased surgical risk: results from the CoreValve US Pivotal Trial. JACC Cardiovasc Interv 2015;8:1207–1217. Reynolds MR, Magnuson EA, Wang K, Thourani VH, Williams M, Zajarias A, Rihal CS, Brown DL, Smith CR, Leon MB, Cohen DJ, Investigators PT. Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results from the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial (Cohort A). J Am Coll Cardiol 2012;60:548–558. Thourani VH, Jensen HA, Babaliaros V, Kodali SK, Rajeswaran J, Ehrlinger J, Blackstone EH, Suri RM, Don CW, Aldea G, Williams MR, Makkar R, Svensson LG, McCabe JM, Dean LS, Kapadia S, Cohen DJ, Pichard AD, Szeto WY, Herrmann HC, Devireddy C, Leshnower BG, Ailawadi G, Maniar HS, Hahn RT, Leon MB, Mack M. Outcomes in nonagenarians undergoing transcatheter aortic valve replacement in the PARTNER-I Trial. Ann Thorac Surg 2015;100:785–792, discussion 793.
0002-9149/© 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2017.07.024
with the introduction of transcatheter aortic valve implantation (TAVI). Since the first clinical use in 2002, TAVI has emerged to be the preferred treatment in inoperable and high surgical risk patients, and has become a component of some TAVI procedures to facilitate successful valve implantation.6,7 Due to the introduction of TAVI, the role of BAV in the management of patients with severe AS has changed. This is the first prospective study to investigate the contemporary role and outcomes of BAV in the TAVI era. Methods This is a prospective, 2-center study of 100 high-risk patients undergoing BAV for management of severe AS. Patients were enrolled in the study from July 2013 through June 2014. Before the procedure, physicians assigned the intent of performing BAV as (1) a bridge to decision whether to treat (BTD); (2) therapeutic bridge to planned therapy (BTX) to improve candidacy; or (3) palliation only (PAL). This designation was derived by consideration of patient demographics, current clinical status, as well as frailty parameters. All patients underwent clinical assessment at 30 days to determine eligibility for definitive valve therapy and functional outcomes. Baseline demographics were recorded as per the Society of Thoracic Surgeons (STS) definitions. Frailty was assessed using serum albumin, gait speed, Katz activities of daily living score, and grip strength.8 All patients were followed up to 1 year, with outcomes measured including www.ajconline.org
Valvular Heart Disease/Prospective Study of BAV
procedural complications, 30-day and 1-year mortality, and definitive valve therapy by SAVR or TAVI. Quality of life (QoL) was measured by the Kansas City Cardiomyopathy Questionnaires (KCCQ), using the 12-question short form.9 All patients underwent individual informed consent for the study, and the study was approved by the Institutional Review Board at both hospitals. Patient demographic data were tabulated according to the indication for BAV: (1) BTD; (2) BTX; or (3) Palliation (PAL). Unadjusted chi-square tests for categorical variables and Wilcoxon rank-sum tests for continuous variables were used to compare baseline demographics between BTD versus BTX. The PAL group (n = 4) was not considered in the statistical comparisons due to the low sample size. A Bonferroni correction was used to correct for multiplicity in baseline comparisons. The mean differences in aortic valve area (AVA) pre- and post-BAV were compared within each BAV indication using unadjusted paired t tests. Kaplan-Meier curves were generated to depict unadjusted 1-year survival rate for the BTD and BTX groups. Additionally, a Cox model adjusted for the STS predicted risk of mortality10 (modeled with a 5-knot restricted cubic spline),11,12 and valve therapy (yes/no) was used to estimate survival rate for BTD and BTX patients. Unadjusted means and standard deviations for patient KCCQ summary scores were reported by study period (baseline, 30 days, 3 months, 6 months, and 1 year). To assess the impact of BAV on QoL 30 days after procedure, a general linear model accounting for patients’ repeated measures was developed. The KCCQ summary score (baseline and 30day) was the model outcome, and the STS predicted risk of mortality and an indicator variable for the baseline KCCQ score (vs 30-day) were the independent variables. This analysis was repeated for the subgroups of BTD and BTX patients. Two of the patients in the BTD and BTX cohorts were missing baseline KCCQ scores and were thus not included in the analysis. Due to the small sample, the impact of BAV on 30-day QoL for the PAL group was assessed using the general linear model with 1 independent variable only: the indicator variable for the baseline KCCQ score (vs 30 days). BAV was performed by a standard technique using Tyshak II, Z-Med, and Z-Med X balloons (B. Braun Medical Inc., Bethlehem, Pennsylvania) ranging from 22 to 30 mm in diameter based on aortic annular size by transthoracic echocardiogram or computed tomography. Peak and mean aortic valve gradients and thermodilution cardiac outputs were recorded. The AVA was calculated using the continuity equation. Serial inflations were performed during rapid ventricular pacing (180 to 200 beats/min), which continued until the balloon was deflated. Valvuloplasty was considered complete when the largest diameter balloon appropriate for the patient’s annular size was utilized and/or a 50% decrease in mean aortic valve gradient was measured. At the end of the procedure, peak and mean gradients were recorded and AVA calculated.
1367
York Heart Association (NYHA) congestive heart failure (Table 1). No significant differences in baseline demographics were observed in the study population when comparing the BTD and BTX groups, except peripheral vascular disease was more common in the BTX group (60.0% vs 25.0%, p = 0.05). A 4-point frailty evaluation was performed in all patients, with 37% and 5% of patients in the BTD and BTX groups, respectively, failing 2 out of 4 of these tests. The types of transcatheter valves used in the 47 patients who underwent TAVI included the following: Sapien (n = 13), Sapien XT (n = 9), Sapien 3 (n = 14), unknown Sapien valve (placed out of state, n = 1); and CoreValve (n = 10). Intention and treatment outcomes in the 100 patients enrolled are shown in Figure 1: 76 BTD; 20 BTX; and 4 PAL. At 30 days, all 3 study groups obtained significant increases in AVA measured by echocardiogram compared with baseline (Table 2). A 30-day mortality for all patients was 6 of 100 (6.0%). One of these patients was in the PAL cohort and 5 were in the BTD cohort and not referred for definitive valve therapy. There was no procedural mortality in patients who underwent TAVI or SAVR. Other complications after BAV included cerebrovascular event in 2 of 100 (2.0%) and acute kidney injury in 2 of 100 (2.0%). The majority of patients in the BTD and BTX groups were discharged to home after BAV (71.1% and 80.0%, respectively). Overall 1-year mortality for the study was 41 of 100 patients (41.0%). In BTD patients, mortality at 1 year was 33 of 76 (43.4%), whereas in BTX patients 1-year mortality was 5 of 20 (25.0%). One-year mortality in the PAL group was 3 of 4 (75.0%). When all patients who received definitive valve therapy are considered, the 1-year mortality was 6 of 54 (11.1%). In the BTD group, 5 of the patients died within 1 year (4 TAVI and 1 SAVR), and these deaths occurred at 33, 54, 206, 282, and 302 days after procedure. In the BTX group, 1 patient who underwent SAVR died within 1 year, and this death occurred at 105 days after procedure. Patients who did not receive definitive valve therapy (excluding the PAL patients) experienced 1-year mortality in 32 of 42 cases (76.2%) (Figure 2). Patients in the BTD arm who received definitive valve therapy had a 1-year mortality of 13.2% (5 of 38) and in the BTX arm had a 1-year mortality of 6.3% (1 of 16). The majority of patients in this study who underwent definitive valve therapy were referred for TAVI (33 of 38 in BTD and 14 of 16 in BTX); with the remainder receiving SAVR. The adjusted analysis of KCCQ summary scores showed that overall 30-day KCCQ scores were significantly improved from baseline (Figure 3), although only the BTD patients showed significant KCCQ summary scores at 30 days in the subgroup analysis. An evaluation of the unadjusted KCCQ scores at each time point demonstrates the largest increase from 30 days to 3 months, likely related to referral for definitive valve therapy with similar values at 6 months and 1 year (Table 3). Further statistical analysis was not done with the later KCCQ values given the primary influence of definitive valve therapy on the change and not effects of the BAV procedure.
Results The patients had a mean (±standard deviation) age of 80.6 (±9.6) years, mean STS predicted risk of mortality of 11.4% (±7.1%), and 91 (91.0%) patients were class III or IV New
Discussion Early studies reported BAV procedural success rates between 80% and 90%; however, the procedure was associated
1368
The American Journal of Cardiology (www.ajconline.org)
Table 1 Patient demographic characteristic by balloon aortic valvuloplasty indication Preoperative Characteristic: Age (years) Women White Black Other Body mass index (kg/m2) Diabetes mellitus End Stage Renal Disease Hypertension Failed 2/4 Frailty Tests Hand Grip Strength Katz Activities of Daily Living 5 meter walk time (minutes) Serum albumin Severe Liver Disease Coronary artery disease Peripheral vascular disease Cerebrovascular disease Cerebrovascular accident Myocardial infarction Ejection fraction NYHA Class I II III IV Prior coronary bypass Prior valve surgery STS predicted risk of mortality
Bridge to Decision (BTD) (n = 76)
Bridge to Therapy (BTX) (n = 20)
p-Value*
Palliation (n = 4)
80.0 ± 9.9 48.7%
82.2 ± 6.1 40.0%
>0.99 >0.99 >0.99
83.5 ± 19.4 50.0%
85.5% 5.3% 9.2% 28.6 ± 10.5 39.5% 5.5% 86.8% 37.0% 17.9 ± 9.7 4.7 ± 1.6 8.7 ± 7.0 3.2 ± 0.4 2.7% 63.2% 25.0% 26.3% 15.8% 21.1% 42.1 ± 16.8%
95.0% 0.0% 5.0% 28.2 ± 6.2 40.0% 5.0% 85.0% 5.0% 18.6 ± 10.6 5.2 ± 1.1 8.2 ± 5.8 3.4 ± 0.5 0.0% 50.0% 60.0% 40.0% 10.0% 20.0% 50.3 ± 10.9%
0.0% 5.3% 17.1% 77.6% 32.9% 0.0% 11.6 ± 6.9
5.0% 5.0% 20.0% 70.0% 20.0% 5.0% 10.3 ± 6.1
>0.99 >0.99 >0.99 >0.99 0.10 >0.99 >0.99 >0.99 >0.99 >0.99 >0.99 0.05 >0.99 >0.99 >0.99 0.25 >0.99
>0.99 0.85 >0.99
100.0% 0.0% 0.0% 27.2 ± 12.5 50.0% 0.0% 100.0% — 16.0 ± 2.8 6.0 ± 0.0 6.5 ± 1.1 3.5 ± 0.5 — 25.0% 25.0% 25.0% 25.0% 0.0% 55.0 ± 21.6% 0.0% 25.0% 25.0% 75.0% 25.0% 0.0% 16.6 ± 10.0
NYHA = New York Heart Association; STS = Society of Thoracic Surgery. * Un-adjusted p-value comparing BTD versus BTX with Bonferroni correction for multiplicity.
with complication rates up to 30% and mortality up to 14%.2,13 More recent data from Eltchaninoff and colleagues reported a major complication rate of 6.8% and an in-hospital mortality rate of 2.5%, with a procedural success rate of 81%.14 These studies, however, are limited by lack of knowledge regarding intent or clinical goals of the BAV procedure. We, therefore, performed this prospective study to evaluate contemporary indications and outcomes by assigned intent before the BAV procedure. In our study, we report significantly increased AVA with low complication rates in a high-risk population of AS patients undergoing BAV. Next, we discuss the role of BAV for PAL, BTD, and BTX in the treatment of AS. In our study we employed BAV for palliation in only 4 patients, with a 75% mortality rate at 1 year. Data from the outcome of patients in the Placement of AoRtic TraNscathetER valves (PARTNER) trial who were unsuitable for SAVR and TAVI and underwent BAV demonstrated, like our study, a high mortality rate of BAV, if AVR is not performed at a later time.15 Although, Kapadia et al did detect an increased survival rate at 3 months in patients undergoing BAV, this difference was not sustained after 6 months. Due to the small sample size of PAL patients in our study, we cannot make any specific conclusions, with larger trials needed to prove that BAV still has a place in the armamentarium of PAL care.
The 2017 American College of Cardiology/American Heart Association guidelines recommend BAV as a bridge to SAVR or TAVI in patients with severe symptomatic AS (class IIB, level of evidence C).16 In our study, BAV as a BTX therapy was performed in 20 patients already considered candidates for definitive valve therapy and in 76 patients, BAV was performed as a bridge to decision. Other studies have demonstrated the clinical benefit of BAV in this bridging role. Doguet and colleagues showed that BAV could reduce the operative risk score in inoperable patients.17 Kefer and colleagues18 reported BAV resulted in an improved ejection fraction (EF) and decreased brain natriuretic peptide (BNP) plasma level in 22 of 59 (37%) patients with reduced EF (EF <40), with symptomatic improvement and increased 1-year survival rate. Kapadia et al demonstrated that bridging to SAVR with BAV (median time between procedures of 78 days) resulted in acceptable 1-year survival rate (78%).19 TAVI increases the spectrum of patients who are suitable for valve therapy, but outcomes of definitive valve therapy after BAV are not well described. We report a 1-year survival rate of 48 of 54 (88.9%) in patients undergoing definitive valve therapy after BAV as a bridge. There are several ways to explain this high survival rate in our study patients compared with previous reports. One is that BAV is able to successfully bridge patients to definitive valve therapy by optimizing clinical status,
Valvular Heart Disease/Prospective Study of BAV
1369
Figure 1. Assigned intent for BAV and treatment outcomes. BAV = balloon aortic valvuloplasty; SAVR = surgical aortic valve replacement; TAVR = transcatheter aortic valve replacement.
Figure 2. STS risk-adjusted survival curves for BTX and BTD patients by definitive valve therapy adjusted for STS predicted risk of mortality. BTD = bridge to decision; BTX = bridge to therapy; STS = Society of Thoracic Surgeons.
1370
The American Journal of Cardiology (www.ajconline.org)
Table 2 Patient outcomes by balloon aortic valvuloplasty indication
Intraprocedural Outcomes: Mean relative decrease in mean gradient post BAV >50% relative decrease in gradient post BAV Received definitive valve therapy No definitive valve therapy 30-day outcomes: Mean change (cm2) in Aortic Valve Area 30-day mortality Acute Kidney Injury Vascular complications Major Minor Neurological complication Stroke TIA Bleeding Minor Major Length of stay (days) Discharge location Home Long-term Care/Nursing Home/Rehab Other hospital/death Other outcomes: Received definitive valve therapy Days from BAV to valve therapy mean ± SD median (min, max) 1-year mortality
Bridge to Decision (BTD) (n = 73)
Bridge to Therapy (BTX) (n = 19)
Palliation (n = 3)
45.7% (41.2%–50.2%)† 29/73 (39.7%) 14/29 (48.3%) 15/29 (51.7%) (n = 76) +0.31 (0.17–0.45)* 5 (6.6%) 1 (1.3%)
38.0% (30.7%–45.4%)† 5/19 (26.3%) 4/5 (80.0%) 1/5 (20.0%) (n = 20) +0.20 (0.16–0.25)* 0 (0.0%) 1 (5.0%)
50.1% (36.9%–63.2%) 2/3 (66.7%) 0/2 (0%) 2/2 (100.0%) (n = 4) +0.22 (0.03–0.41)* 1 (25.0%) 0 (0.0%)
2 (2.6%) 0 (0.0%)
1 (5.0%) 0 (0.0%)
0 (0.0%) 1 (25.0%)
1 (1.3%) 1 (1.3%)
0 (0.0%) 0 (0.0%)
0 (0.0%) 0 (0.0%)
3 (3.9%) 3 (3.9%) 4.0 ± 4.9
1 (5.0%) 0 (0.0%) 4.1 ± 5.4
0 (0.0%) 0 (0.0%) 3.0 ± 6.0
54 (71.1%) 16 (21.1%) 6 (7.8%)
16 (80.0%) 4 (20.0%) 0 (0.0%)
2 (50.0%) 1 (25.0%) 1 (25.0%)
38 (50.0%)
16 (80.0%)
0 (0.0%)
93 ± 77 64 (19, 307) 33 (43.4%)
48 ± 27 36 (11, 106) 5 (25.0%)
— — 3 (75.0%)
BAV = balloon aortic valvuloplasty; TIA = transient ischemic attack. * Unadjusted paired t-test comparing post-BAV Aortic Valve Area versus pre-BAV Aortic Valve Area (with 95% Confidence Intervals). † Unadjusted paired t-test comparing post-BAV mean gradient versus pre-BAV mean gradient (with 95% Confidence Intervals).
often the presence of congestive heart failure. Secondly, BAV may allow the ability to differentiate those patients with clinical improvement to optimally select appropriate patients for valve therapy. Lastly, this finding may be explained by patient survival rate bias, as the patients undergoing definitive treatment must initially benefit from BAV and survive long enough to receive further therapy. The reevaluation of patients after BAV in the BTX group resulted in 4 patients initially referred for definitive therapy to subsequently not undergo the planned therapy. One patient had severe peripheral arterial disease and underwent below the knee arterial revascularization at the time of BAV due to a nonhealing ulcer. While waiting for wound healing, the patient died 109 days after the BAV. The second patient had significant clinical improvement after BAV and did not wish to pursue TAVI, but was admitted with congestive heart failure (CHF) and died 198 days post-BAV. The third patient had chronic renal insufficiency and was admitted with acute onchronic renal insufficiency and hypotension 11 days after BAV, which progressed, and led to death 35 days later. The fourth patient was admitted 22 days after BAV with a non-ST segment elevation myocardial infarction and underwent coronary stenting, complicated by postprocedure cardiogenic shock, multisystem organ failure, cardiac arrest, and death 33 days after BAV. Of these 4 patients, the third patient’s course appears
directly related to BAV complications, the fourth patient is possibly related, and the first 2 are not related to BAV complications. For patients in the BTD group who were not felt to be TAVI or SAVR candidates after BAV, the 1-year mortality of 28 of 38 (73.7%) was even higher than historical mortality rates of medically treated patients with AS.20,21 This is likely due not only to the high-risk level of our study patients, but also points to the importance of withholding invasive and costly technology in patients who may not meet clinical criteria to realize long-term benefit. It is important to note that this study was not designed to compare the outcomes of the BTD and BTX groups, given the different populations of patients at baseline. Additionally, comparison regarding the outcomes of no definitive valve therapy versus definitive valve therapy after BAV was not the outcome of interest in this study. Lastly, in the BTD and BTX groups; only approximately 40% and 26%, respectively, had postprocedure reduction of at least 50% in the aortic valve gradient. However, the protocol required either maximum size BAV balloon as measured by preprocedure imaging or >50% gradient reduction, which are the common clinical criteria utilized. This report demonstrates the ability of BAV to improve short-term QoL in high-risk patients with AS. Especially in
Valvular Heart Disease/Prospective Study of BAV
1371
Figure 3. Unadjusted and STS risk-adjusted baseline and 40-day KCCQ summary scores by BAV indication with 95% confidence intervals. Adjusted for baseline KCCQ score and STS predicted risk of mortality and accounting for patients’ repeated measures. BAV = balloon aortic valvuloplasty; BTD = bridge to decision; BTX = bridge to therapy; KCCQ = Kansas City Cardiomyopathy Questionnaire; STS = Society of Thoracic Surgeons.
Table 3 Patient Kansas City Cardiomyopathy Questionnaire scores throughout study period Study Period: Unadjusted: Baseline KCCQ summary score 30-day KCCQ summary score 3-month KCCQ summary score 6-month KCCQ summary score 1-year KCCQ summary score Adjusted: All patients Baseline KCCQ summary score 30-day KCCQ summary score Bridge to decision patients Baseline KCCQ summary score 30-day KCCQ summary score‡ Bridge to therapy patients Baseline KCCQ summary score 30-day KCCQ summary score§ Palliative patients Baseline KCCQ summary score 30-day KCCQ summary score
n*
Mean ± SD
n = 94 n = 76 n = 35 n = 22 n=7
34.9 ± 22.0 45.2 ± 27.7 59.3 ± 30.2 60.4 ± 28.8 68.6 ± 37.5 Mean (95% CI)
n = 94 n = 76
33.1 (28.4–37.8) 43.5 (38.3–48.6)
<0.0001
n = 73 n = 57
33.3 (28.3–38.2) 45.1 (39.0–51.1)
0.001
n = 17 n = 12
38.8 (29.5–48.2) 44.6 (12.5–95.1)
0.224
n=4 n=3
49.4 (25.1–73.7) 56.0 (26.4–100)
0.825‖
BAV = balloon aortic valvuloplasty; KCCQ = Kansas City Cardiomyopathy Questionnaire. * n represents number of fully completed KCCQ summary scores at each study period. † Adjusted for baseline KCCQ score and STS predicted risk of mortality and accounting for patients’ repeated measures. ‡ n = 2 bridge to decision patients with 30-day KCCQ were missing baseline KCCQ. § n = 2 bridge to therapy patients with 30-day KCCQ were missing baseline KCCQ. ‖ Unadjusted due to sample size.
p-Value† Not estimated given the primary influence of definitive valve therapy on the change and not effects of the BAV procedure.
1372
The American Journal of Cardiology (www.ajconline.org)
an elderly population, survival rate with a meaningful functional outcome and QoL is paramount. Several studies have shown an improvement of QoL after BAV and TAVI with a stabilization of KCCQ after 6 months.15,22,23 Similar to our findings, Kapadia and colleagues showed an improvement of more than 10 points in the KCCQ overall summary scale at 30 days in patients undergoing BAV in the PARTNER trial.24 We confirm the beneficial impact of BAV on QoL in clinical practice. Even in patients who are not eligible for TAVI, a discussion of the procedural risks versus benefits in terms of QoL may be warranted. The contemporary role of BAV is as an effective tool to optimize the clinical status of selected patients for definitive therapy as well as an effective decision-making tool. We demonstrate in this study a high success rate and low complication rate of BAV in such a role. Additionally, QoL is improved at 30 days with BAV. In summary, BAV is shown to be an effective decision-making tool for patient selection, leading to excellent 1-year survival rate if TAVI or SAVR are performed subsequently.
9. 10.
11. 12. 13. 14.
15.
Acknowledgment: We would like to thank John J. Squiers, BSE, for his editorial support during preparation of this report. Disclosures The authors have no conflicts of interest to disclose. 1. Cribier A, Savin T, Saoudi N, Rocha P, Berland J, Letac B. Percutaneous transluminal valvuloplasty of acquired aortic stenosis in elderly patients: an alternative to valve replacement? Lancet 1986;1:63–67. 2. Percutaneous balloon aortic valvuloplasty. Acute and 30-day followup results in 674 patients from the NHLBI Balloon Valvuloplasty Registry. Circulation 1991;84:2383–2397. 3. Lieberman EB, Bashore TM, Hermiller JB, Wilson JS, Pieper KS, Keeler GP, Pierce CH, Kisslo KB, Harrison JK, Davidson CJ. Balloon aortic valvuloplasty in adults: failure of procedure to improve long-term survival. J Am Coll Cardiol 1995;26:1522–1528. 4. Letac B, Cribier A, Koning R, Bellefleur JP. Results of percutaneous transluminal valvuloplasty in 218 adults with valvular aortic stenosis. Am J Cardiol 1988;62:598–605. 5. Ben-Dor I, Pichard AD, Satler LF, Goldstein SA, Syed AI, Gaglia MA Jr, Weissman G, Maluenda G, Gonzalez MA, Wakabayashi K, Collins SD, Torguson R, Okubagzi P, Xue Z, Kent KM, Lindsay J, Waksman R. Complications and outcome of balloon aortic valvuloplasty in high-risk or inoperable patients. JACC Cardiovasc Interv 2010;3:1150–1156. 6. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Lung B, Lancellotti P, Pierard L, Price S, Schafers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M, ESC Committee for Practice Guidelines (CPG), Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42:S1–S44. 7. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD, American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438–2488. 8. Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA, Popma JJ, Ferrucci L, Forman DE. Frailty assessment in the cardio-
16.
17.
18.
19.
20. 21. 22.
23.
24.
vascular care of older adults. J Am Coll Cardiol 2014;63:747– 762. 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. O’Brien SM, Shahian DM, Filardo G, Ferraris VA, Haan CK, Rich JB, Normand SL, DeLong ER, Shewan CM, Dokholyan RS, Peterson ED, Edwards FH, Anderson RP, Society of Thoracic Surgeons Quality Measurement Task Force. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2—isolated valve surgery. Ann Thorac Surg 2009;88:S23–S42. Filardo G, Hamilton C, Hamman B, Ng HK, Grayburn P. Categorizing BMI may lead to biased results in studies investigating in-hospital mortality after isolated CABG. J Clin Epidemiol 2007;60:1132–1139. Harrell F Jr. Regression modeling strategies: with application to linear models, logistic regression, and survival analysis. New York: SpringerVerlag; 2001. McKay RG. The Mansfield Scientific Aortic Valvuloplasty Registry: overview of acute hemodynamic results and procedural complications. J Am Coll Cardiol 1991;17:485–491. Eltchaninoff H, Durand E, Borz B, Furuta A, Bejar K, Canville A, Farhat A, Fraccaro C, Godin M, Tron C, Sakhuja R, Cribier A. Balloon aortic valvuloplasty in the era of transcatheter aortic valve replacement: acute and long-term outcomes. Am Heart J 2014;167:235–240. Kapadia S, Stewart WJ, Anderson WN, Babaliaros V, Feldman T, Cohen DJ, Douglas PS, Makkar RR, Svensson LG, Webb JG, Wong SC, Brown DL, Miller DC, Moses JW, Smith CR, Leon MB, Tuzcu EM. Outcomes of inoperable symptomatic aortic stenosis patients not undergoing aortic valve replacement: insight into the impact of balloon aortic valvuloplasty from the PARTNER trial (Placement of AoRtic TraNscathetER Valve trial). JACC Cardiovasc Interv 2015;8:324–333. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O’Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A. 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. doi:10.1016/j.jacc.2017.03.011. Doguet F, Godin M, Lebreton G, Eltchaninoff H, Cribier A, Bessou JP, Litzler PY. Aortic valve replacement after percutaneous valvuloplasty— an approach in otherwise inoperable patients. Eur J Cardiothorac Surg 2010;38:394–399. Kefer J, Gapira JM, Pierrard S, DeMeester C, Gurne O, Chenu P, Renkin J. Recovery after balloon aortic valvuloplasty in patients with aortic stenosis and impaired left ventricular function: predictors and prognostic implications. J Invasive Cardiol 2013;25:235–241. Kapadia SR, Goel SS, Yuksel U, Agarwal S, Pettersson G, Svensson LG, Smedira NG, Whitlow PL, Lytle BW, Tuzcu EM. Lessons learned from balloon aortic valvuloplasty experience from the pre-transcatheter aortic valve implantation era. J Interv Cardiol 2010;23:499–508. Schwarz F, Baumann P, Manthey J, Hoffmann M, Schuler G, Mehmel HC, Schmitz W, Kubler W. The effect of aortic valve replacement on survival. Circulation 1982;66:1105–1110. Ross J Jr, Braunwald E. Aortic stenosis. Circulation 1968;38:61–67. Arnold SV, Reynolds MR, Wang K, Magnuson EA, Baron SJ, Chinnakondepalli KM, Reardon MJ, Tadros PN, Zorn GL, Maini B, Mumtaz MA, Brown JM, Kipperman RM, Adams DH, Popma JJ, Cohen DJ, CoreValve US Pivotal Trial Investigators. Health status after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis at increased surgical risk: results from the CoreValve US Pivotal Trial. JACC Cardiovasc Interv 2015;8:1207–1217. Reynolds MR, Magnuson EA, Wang K, Thourani VH, Williams M, Zajarias A, Rihal CS, Brown DL, Smith CR, Leon MB, Cohen DJ, Investigators PT. Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results from the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial (Cohort A). J Am Coll Cardiol 2012;60:548–558. Thourani VH, Jensen HA, Babaliaros V, Kodali SK, Rajeswaran J, Ehrlinger J, Blackstone EH, Suri RM, Don CW, Aldea G, Williams MR, Makkar R, Svensson LG, McCabe JM, Dean LS, Kapadia S, Cohen DJ, Pichard AD, Szeto WY, Herrmann HC, Devireddy C, Leshnower BG, Ailawadi G, Maniar HS, Hahn RT, Leon MB, Mack M. Outcomes in nonagenarians undergoing transcatheter aortic valve replacement in the PARTNER-I Trial. Ann Thorac Surg 2015;100:785–792, discussion 793.