Author + information
- Received April 26, 2010
- Revision received June 21, 2010
- Accepted August 5, 2010
- Published online November 1, 2010.
- Itsik Ben-Dor, MD,
- Augusto D. Pichard, MD,
- Lowell F. Satler, MD,
- Steven A. Goldstein, MD,
- Asmir I. Syed, MD,
- Michael A. Gaglia Jr, MD, MSc,
- Gaby Weissman, MD,
- Gabriel Maluenda, MD,
- Manuel A. Gonzalez, MD, MPH,
- Kohei Wakabayashi, MD,
- Sara D. Collins, MD,
- Rebecca Torguson, MPH,
- Petros Okubagzi, MD,
- Zhenyi Xue, MS,
- Kenneth M. Kent, MD, PhD,
- Joseph Lindsay, MD and
- Ron Waksman, MD⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Ron Waksman, Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010
Objectives This study aimed to determine the success, complications, and survival of patients after balloon aortic valvuloplasty (BAV).
Background The introduction of transcatheter aortic valve implantation (TAVI) BAV has led to a revival in the treatment of patients with severe aortic stenosis.
Methods A cohort of 262 patients with severe aortic stenosis underwent 301 BAV procedures. Of these, 39 (14.8%) patients had ≥2 BAV procedures. Clinical, hemodynamic, and follow-up mortality data were collected.
Results The cohort mean age was 81.7 ± 9.8 years, and the mean Society of Thoracic Surgeons and logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 13.3 ± 6.7 and 45.6 ± 21.6, respectively. BAV was performed as a bridge to TAVI or to surgical aortic valve replacement in 28 patients (10.6%) and for symptom relief in 234 (89.4%). The mean aortic valve area (AVA) increased from 0.58 ± 0.3 cm2 to 0.96 ± 0.3 cm2 (p < 0.001). Of these, 111 (45.0%) had final AVA >1 cm2, and in 195 patients (79%), AVA increased by >40%. De novo BAV resulted in a higher mean increase in AVA 0.41 ± 0.24 cm2 versus 0.28 ± 0.24 cm2 in redo BAV (p = 0.003). Serious adverse events occurred in 47 patients (15.6%), intraprocedural death in 5 (1.6%), stroke in 6 (1.99%), coronary occlusion in 2 (0.66%), severe aortic regurgitation in 4 (1.3%), resuscitation/cardioversion in 5 (1.6%), tamponade in 1 (0.33%), and permanent pacemaker in 3 (0.99%). A vascular complication occurred in 21 patients (6.9%); 34 (11.3%) had a post-procedure rise in creatinine >50%; and 3 (0.99%) required hemodialysis. During median follow-up of 181 days, the mortality rate was 50% (n = 131). The mortality rate in the group with final AVA >1 cm2 was significantly lower than in the group with final AVA of <1 cm2 (36.4% vs. 57.9%, p < 0.001). Final AVA was associated with lower mortality (hazard ratio: 0.46, p = 0.03). BAV as a bridge to TAVI or surgical aortic valve replacement had a better outcome compared with BAV alone: mortality rate 7 (25%) versus 124 (52.9%), respectively (p < 0.0001).
Conclusions Long-term survival is poor after BAV alone. BAV as a bridge to percutaneous or surgical aortic valve replacement is feasible, safe, and associated with better outcome than BAV alone.
Critical aortic stenosis (AS) affects an estimated 4.6% of individuals over 75 years of age (1). Aortic valve replacement surgery is the treatment of choice for symptomatic calcific AS. The prognosis is poor for patients with severe symptomatic AS without surgical treatment, with an average survival of only 1 to 3 years after symptom onset (2). Despite these facts, many symptomatic patients do not undergo operation due to high operative risk owing to their multiple comorbidities. In the Euro Heart Survey (3), 31.8% of patients received no surgical valve replacement despite indication. Transcatheter aortic valve implantation (TAVI) is under study as an alternative treatment modality for high-risk, severe, symptomatic AS.
Many patients with severe, symptomatic AS who are screened for TAVI trials and are found not eligible based on strict inclusion/exclusion criteria are referred for balloon aortic valvuloplasty (BAV). BAV, introduced by Cribier et al. (4) in 1986, is a useful, palliative treatment for symptomatic relief and can be used as a bridge to more definitive surgical replacement or TAVI in hemodynamically unstable patients (5). The aim of this study was to determine the success, complication rates, and survival of patients after BAV and to define the clinical, invasive, and echocardiographic variables related to long-term outcome after this procedure.
From January 2000 to December 2009, the data from 301 BAV procedures in 262 consecutive patients with severe symptomatic AS were prospectively entered into a dedicated database. The cohort consisted of 31 patients (11.8%) from the pre-TAVI era, 29 (11.0%) were included in the BAV arm of the TAVI trial, and 28 (10.6%) had BAV as a bridge for surgical valve replacement or TAVI. Of the remaining 174 patients excluded from the TAVI trial, 49 (28.1%) had >1 exclusion criteria. The main exclusion criteria were peripheral vascular or aorta disease in 40 patients (17.9%), significant coronary artery disease requiring revascularization in 37 (16.5%), renal failure in 23 (10.3%), ejection fraction <20% in 22 (9.8%), low Society of Thoracic Surgeons (STS) score <10% in 16 (7.1%), other significant valvular disease in 15 (6.7%), aortic valve area >0.8 cm2 in 13 (5.8%), and others (e.g., neurological disease, unstable, refuse, bleeding diathesis, large-size annulus) in 57 (25.5%). All patients had severe, symptomatic AS confirmed by transthoracic echocardiography and hemodynamic evaluation. Patients were referred for BAV for palliation of heart failure symptoms, treatment of cardiogenic shock, and, as a bridge for TAVI, surgical aortic valve replacement or noncardiac surgery. The STS score and the logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) were calculated for all patients. In-hospital clinical events were determined from the review of medical records. Follow-up was obtained by trained medical personnel using direct telephone interviews and review of medical records both in-hospital and during follow-up outpatient physician visits.
Echocardiography was performed with commercially available ultrasound systems. All patients underwent a comprehensive examination that included M-mode, 2-dimensional echocardiography, and conventional and color Doppler by an experienced echocardiographer before and after BAV. Multiple transducer positions were used to record peak aortic jet velocities, and aortic valve area (AVA) was calculated with the continuity equation.
Diagnostic right and left heart catheterization was performed on all patients. Heparin was administrated in all patients 10 to 70 U/kg after 9- to 13-F sheath insertion in the femoral artery. BAV was performed according to standard techniques via the retrograde femoral approach in all patients except 1. In that individual, axillary artery access was employed because of severe peripheral vascular disease. Equalization of pressures was documented before entering the left ventricle. The gradient was confirmed with pullback gradient measurements. Peak and mean gradients were measured, and AVA was calculated with the Gorlin formula.
The sinotubular junction is the site prone to rupture during a BAV procedure. We analyzed the minimal diameter of the sinotubular junction by aortogram in the left anterior oblique with a marker pigtail and by echocardiography. The chosen balloon size was 3 to 5 mm under this measurement. To stabilize the balloon position across the valve, the heart was paced at a high rate (180 to 200 beats/min) until the blood pressure fell to <50 mm Hg before inflation. Pacing was continued until the balloon was fully deflated. Additional BAV procedures were performed subsequently in cases in which the mean gradients did not decrease significantly (∼30% to 40%), and a larger balloon was employed in selected cases in which the initial balloon size failed to significantly decrease gradients (∼30% to 40%). At the end of the procedure, measurements of cardiac output and pressure gradients and calculations were repeated. After BAV, an aortogram was performed to assess aortic regurgitation. Arterial puncture sites were closed with closure devices (6-F Perclose [Abbott Laboratories, Abbott Park, Illinois] or 12-F Prostar [Abbott] or 8-F Angio-Seal [St. Jude Medical, St. Paul, Minnesota]). If the device failed, manual compression was applied. Serious adverse events were defined as intraprocedural death, stroke, coronary occlusion or dissection, moderate-to-severe aortic regurgitation, profound hypotension requiring resuscitation and intubation or cardioversion, tamponade, permanent pacemaker requirement, and vascular complication requiring intervention.
Continuous variables are presented as mean ± SD and categorical variables are presented as percentages. Days of follow-up are presented as median (25th, 75th percentiles). Differences between continuous variables were assessed by Student t test. Paired tests were analyzed by paired Student t test. Categorical variables were compared using the chi-square test or Fisher exact test as indicated. Significance was set at p < 0.05. Cumulative survival curves were constructed using the Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazard regression method was used to examine the univariable association of clinical, catheterization, and echocardiographic variables with event-free survival. Multivariable associations within these same groups were also evaluated. All continuous variables were measured in their original scale.
The cohort included 262 patients who underwent 301 BAV procedures. Among these patients, 29 underwent 2 BAV, 8 underwent 3 BAV, and 2 underwent 4 BAV procedures. Of the 301 BAV procedures, 114 (37.8%) were done with concomitant diagnostic coronary angiography and 52 (17.2%) were done with concomitant percutaneous coronary intervention. After the introduction of TAVI, there was a steep increase in the number of procedures performed each year; most of the patients were screened for the trial but were not eligible based on the inclusion/exclusion criteria (Fig. 1). Indications for the BAV procedures included symptom relief in 210 (80.2%), cardiogenic shock in 24 (9.1%), bridge for TAVI in 13 (4.9%), and bridge for surgical aortic valve replacement in 15 (5.7%) (Fig. 2).
Baseline characteristics are displayed in Table 1. The patients were at high risk with a mean age of 81.7 ± 9.8 years and mean STS and a logistic EuroSCORE of 13.3 ± 6.7 and 45.6 ± 21.6, respectively. Laboratory values, echocardiographic data, and right heart catheterization data before and after BAV are presented in Table 2.
The mean AVA by invasive hemodynamic data increased from 0.58 ± 0.3 cm2 to 0.96 ± 0.3 cm2 (p < 0.001). Of these, 111 (45.0%) had final AVA >1 cm2. In 195 patients (79.0%), the AVA increased by >40%. After the initial BAV, the mean increase in valve area was 0.41 ± 0.24 cm2 higher compared with the group who had redo BAV, with a mean increase in AVA of only 0.28 ± 0.24 cm2 (p = 0.003).
The median hospital duration was 4 days (interquartile range [IQR]: 2.8 days). Fifty-three patients (17.6%) required blood transfusion. A rise in creatinine >50% was observed in 34 patients (11.3%). Three (0.99%) required hemodialysis. The mean rise in troponin was 1.1 ± 2.5 ng/dl and in creatine kinase-myocardial band was 2.94 ± 5.0 U/l. Serious adverse events occurred in 47 patients (15.6%) (Table 3).
During a median follow-up of 181 days (IQR: 56, 436 days) the mortality rate was 50% (n = 131). The median time from BAV to death was 95.5 days (IQR: 24.5, 252.75 days) (Fig. 3). Final valve area was associated with lower mortality (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.22 to 0.95, p = 0.03). However, the absolute increase in AVA and the percentage increase in valve area were not associated with lower mortality (HR: 0.48, 95% CI: 0.19 to 1.22, p = 0.12) and (HR: 1.00, 95% CI: 0.99 to 1.01, p = 0.22), respectively. The mortality of the group with final AVA >1 cm2 was significantly lower than the group with final AVA of <1 cm2 (36.4% vs. 57.9%, p < 0.001); however, there was no significant difference between the 2 groups with increased valve areas of >40% vs. <40% (49.7% vs. 50.9%, respectively, p = 0.7). Balloon aortic valvuloplasty as a bridge to TAVI or surgical aortic valve replacement, when compared with BAV alone, had a better outcome: mortality rate 7 (25%) versus 124 (52.9%), respectively (p < 0.0001) (Fig. 4).
Clinical and laboratory values, echocardiographic data, right heart catheterization data, and procedural factors associated with mortality are presented in Table 4. After multivariable adjustment, the strongest predictors for mortality were New York Heart Association functional class IV (HR: 4.91, 95% CI: 1.88 to 12.8, p = 0.01), baseline renal failure (HR: 2.23, 95% CI: 1.46 to 2.98, p = 0.01), pulmonary systolic pressure (HR: 1.03, 95% CI: 1.01 to 1.06, p = 0.01), hematocrit drop (HR: 1.16, 95% CI: 1.04 to 1.3, p = 0.01). Balloon aortic valvuloplasty as a bridge for definitive therapy was independently associated with lower mortality failure (HR: 0.10, 95% CI: 0.01 to 0.93, p = 0.04).
Our study confirms an exceedingly poor prognosis for patients with symptomatic severe AS undergoing BAV–with mortality rates of up to 50% at a median follow-up period of 6 months. This observation is in accordance with rates previously reported. Liberman et al. (6) found survival rates of 52%, 31%, and 18% at 1, 2, and 3 years after BAV, respectively. Otto et al. (7) reported 55% survival at 1 year, 35% at 2 years, and 23% at 3 years. Initial enthusiasm in the late 1980s for BAV in adults with calcific AS was subsequently tempered by studies demonstrating that although there was initial symptomatic improvement (8), it was associated with high complication and recurrence rates (9), and little impact on long-term survival, therefore, the procedure was rarely undertaken (7). With the introduction of TAVI, there has been a resurgence in BAV. At our center, the number of BAV procedures performed increased from 4.4 annually to 88.6 after the introduction of TAVI.
Multiple modifications have been made in the BAV technique over the years. Rapid ventricular pacing during BAV enables precise and stable balloon positioning. This technique was reported recently to result in a lesser increase in AVA when compared with performing the procedure without rapid ventricular pacing (0.24 ± 0.2 vs. 0.38 ± 0.3, p < 0.01) (10). The mean increase in AVA in our study was 0.4 ± 0.25 cm2 when >90% of the procedures were done with rapid ventricular pacing. Vascular complications have been lowered from the previously reported 13.5% (11) to 6.9%. This improvement may be attributed to the newer balloon catheter that allows the use of a 10-F sheath instead of a 13-F sheath, as well as the availability of closure devices. Moreover, most of our patients had an assessment of the peripheral vascular tree by contrast computer tomography as a part of screening for TAVI, thereby allowing us to choose the better side for a safer vascular approach. These changes and others have led to overall lower complication rates. In our series, we experienced a 16.2% severe complication rate compared with 31% reported previously (8). The duration of hospitalization after the procedure was shorter, with a mean length of stay of 4 days compared with the previously reported 7.6 days (8).
The overall change in AVA in our study from 0.58 ± 0.3 cm2 to 0.96 ± 0.3 cm2 is higher than was previously reported in other large series (n = >100). In the National Heart Lung and Blood Institute Balloon Valvuloplasty Registry, the AVA increased from 0.5 to 0.8 cm2 (7). In the Mansfield registry, the AVA increased from 0.5 to 0.82 cm2 (12), whereas Liberman et al. (6) reported an increase in AVA from 0.5 to 0.7 cm2. Agarwal et al. (11) reported an increase from 0.61 to 1.2 cm2. Patients subjected to redo BAV had significantly lower AVA post-procedure when compared with patients with de novo BAV (0.28 ± 0.24 cm2 vs. 0.41 ± 0.24 cm2, p < 0.001). These data are in concordance with Kuntz et al. (13), who reported a lower post-valvuloplasty AVA in patients after repeat BAV compared with the first procedure. Feldman et al. (14) found in a series of 85 patients less improvement in AVA after the second BAV compared with the first BAV (0.2 ± 0.13 cm2 vs. 0.45 ± 0.17 cm2, p < 0.01).
Restenosis is evident as early as a few days after BAV. Young scar tissue gradually fills up splits between commissures, small tears or lacerations in the collagenous valve stroma, and fractures in calcifications (15,16). Histologic changes in restenosed valves differ from those seen initially in calcific AS, with granulation tissue, fibrosis, and ossification being present (13). This process may lead to limited results of second dilations.
Predictors of mortality
Predictors of mortality in patients undergoing BAV have been previously reported (7,17). In the largest series of patients undergoing BAV, multivariate analysis demonstrated baseline functional status, baseline cardiac output, renal function, cachexia, female sex, left ventricular systolic function, and mitral regurgitation as independent predictors of mortality (7). The present study detected New York Heart Association functional class IV as a predictor for mortality. This is not surprising because functional status is a well-known determinant of prognosis in patients with severe AS treated medically (18,19). Renal insufficiency was an independent predictor for mortality; in previous studies (20–22), renal failure was reported to be associated with worse outcomes in high-risk patients undergoing aortic valve replacement surgery. High pulmonary artery pressure in our cohort and in other series was associated with poor outcome as well (23). As opposed to other cardiovascular disease, we found women to have higher survival rates than men (Table 4).
BAV as a bridge to TAVI/surgical aortic valve replacement
In our study, the outcome of patients who had the BAV procedure as a bridge to TAVI or surgical aortic valve replacement was much better when compared with patients who had the BAV procedure only. Kuntz et al. (24) reported better actuarial event-free survival of octogenarians after surgical aortic valve replacement compared with 205 patients treated by BAV. Some patients who initially had BAV as an alternative to surgical aortic valve replacement or TAVI because of prohibitive perioperative risks may later become candidates at the time of restenosis (25). Balloon aortic valvuloplasty should be followed by more definitive treatment in all suitable cases. Other studies reported bridging to TAVI with BAV as a feasible and reasonably safe approach to offer temporary relief in selected high-risk patients with symptomatic severe AS and a high chance of periprocedural complications (26,27).
This retrospective, observational report has several limitations. Among them are the long time period, which included change in technique and the lack of a control group. However, this is among the largest series of patients reported in the literature. The definition of successful BAV as final AVA >1 cm2 associated with a lower mortality rate should be viewed with caution due to the lack of a control group, which was treated medically only. A prospective, randomized study comparing valvuloplasty to medical therapy is necessary to define the true potential survival benefit from BAV. The high mortality/morbidity rates in this group of patients may have been influenced by the number of patients with very severe comorbidities evaluated for the TAVI trial.
Long-term survival is dismal after BAV alone. Transcatheter or surgical aortic valve replacement should be pursued because BAV as a bridge to transcatheter or surgical aortic valve replacement is feasible, safe, and associated with better outcome than BAV alone. This may be especially true in patients who develop restenosis after the first BAV because the second BAV is associated with a lesser increase in AVA.
The authors have reported that they have no relationships to disclose.
- Abbreviations and Acronyms
- aortic stenosis
- aortic valve area
- balloon aortic valvuloplasty
- Society of Thoracic Surgeons
- transcatheter aortic valve implantation
- Received April 26, 2010.
- Revision received June 21, 2010.
- Accepted August 5, 2010.
- American College of Cardiology Foundation
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