Short-Term Efficacy of Palliative Balloon Aortic Valvuloplasty in Selected Patients with High Operative Risk

Abstract: With the introduction of transcatheter aortic valve implantation (TAVI), the precise role of balloon aortic valvuloplasty (BAV) remains to be established. Methods. Between August 2008 and November 2010, consecutive patients undergoing BAV for severe aortic stenosis (AS) in our center were enrolled. The primary endpoint was survival to hospital discharge. Secondary endpoints were 30-day survival and progression to aortic valve replacement (AVR). Results. Enrolled were 64 patients (age, 82 ± 8 years; 45% male). Treatment objectives were: symptom palliation (69%); potential AVR (23%); and facilitation of withdrawal of ventilation or non-cardiac surgery (8%). At baseline, patients had logistic EuroSCORE of 35.7 ± 19.5, NT-proBNP of 11,195 ± 11,694 ng/L, aortic valve area of 0.53 ± 0.17 cm², and peak transaortic gradient (PG) of 75.2 ± 25.3 mm Hg. The primary endpoint of survival to hospital discharge was reached by 97% patients. The secondary endpoint of 30-day mortality occurred in 8 patients (13%). Overall, 12 patients showed clinical improvement within 1 month of BAV. Of these, 8 patients underwent AVR (TAVI in 3/8 [38%]). After multivariate adjustment, the strongest correlates for 30-day survival and progression to AVR pre-BAV were: New York Heart Association ≤II, SBP ≥90 mm Hg, estimated glomular filtration rate ≥45 mL min-1, left ventricular ejection fraction ≥45% and transaortic PG <80 mm Hg. Conclusion. In patients with severe AS and high operative risk, BAV has the potential to facilitate progression to TAVI in those who are technically suitable.

J INVASIVE CARDIOL 2012;24:58-62

Key words: aortic stenosis, balloon aortic valvuloplasty, transcatheter aortic valve implantation

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Aortic stenosis (AS) is the most common valvular lesion in the ageing population, with a prevalence of 4.6% in adults ≥75 years of age.^1-3 Following an often prolonged latency period, AS is rapidly progressive once symptoms occur, with a high mortality rate among untreated patients.^3-5 Surgical aortic valve replacement (SAVR) is the recommended treatment for symptomatic patients or those with left ventricular (LV) systolic dysfunction,^6-9 and is associated with low operative mortality in those without significant co-morbidity.¹⁰ However, in clinical practice, approximately 30% of patients with severe AS do not undergo AVR,^3,8,11 in part due to advancing age and the presence of multiple coexisting conditions.^3,8 As a consequence, transcatheter aortic valve implantation (TAVI), a less invasive procedure where a bioprosthetic valve is implanted within the diseased native aortic valve, has emerged as a viable treatment option in this high-risk patient group.

Percutaneous balloon aortic valvuloplasty (BAV) is an established though limited treatment for symptomatic AS in elderly patients in whom SAVR is not an option.^12,13 While BAV does not confer any long-term survival benefit, some studies have shown a mortality benefit at 1 year.^12,14 BAV has the potential to: (1) palliate symptoms in those patients considered too high risk or clinically inappropriate for AVR; (2) evaluate the contribution of AS to symptoms in patients with multiple co-morbidities, especially concomitant respiratory disease; (3) unmask recoverable LV function in those with poor ejection fraction but contractile reserve; and (4) act as a bridge to definitive valve replacement, whether SAVR or TAVI. However, the prospective identification of patients most likely to benefit from BAV and progress to definitive therapy remains a challenge. Hence, the precise role of BAV in the current TAVI era remains ill-defined.

In this study, we aim to evaluate the role of BAV in treating patients with severe symptomatic AS in a TAVI-active tertiary referral center and identify preprocedural characteristics that may aid clinical management decisions in these patients.

Methods

Patient population. In this study, consecutive patients undergoing isolated BAV for severe AS between 01 August 2008 and 30 November 2010 were enrolled. Patients receiving BAV as part of a TAVI procedure (Table 1) were excluded. The study cohort included patients with symptomatic severe AS at high surgical risk, those considered non-operable, and those referred for consideration of TAVI. All cases were reviewed at the Heart Valve Team/Cardiac Surgical conference.

Screening assessment. Prior to BAV, all patients underwent interview, clinical assessment, electrocardiogram (ECG), and standard echocardiogram including calculation of transaortic flow gradient and valve area according to the recommendations of the American Society of Echocardiography.¹⁵ In addition, all patients had blood sampled for preprocedural hemoglobin (Hb) concentration, estimated glomerular filtration rate (eGFR) and N-terminal pro-brain natriuretic peptide (NT-proBNP) titre. Society of Thoracic Surgeons (STS) score and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) were calculated using the Web-based systems (https://www.euroscore.org and https://209.220.160.181/STSWebRiskCalc261/de.aspx). All patient data, including demographics, were prospectively entered into a dedicated database.

BAV procedure. BAV was performed retrogradely using a standard technique.¹⁸ The LV-aortic pressure gradient was measured with dual transducers. Coronary angiography was performed pre-BAV, with percutaneous coronary intervention performed if indicated. The diameter of the balloon catheter was selected after measurement of the aortic annulus diameter using two-dimensional echocardiography. The balloon was manually inflated for 5-10 seconds. In most patients, rapid pacing was used (typically at a rate of 180-200 beats/min) to produce a decrease in systolic blood pressure ≤50 mm Hg during balloon inflation. The transaortic valve gradient was reassessed after successful balloon inflation and compared with that pre-procedure.

Indications, postprocedural assessment, and endpoints. The principal indication for BAV in each patient was recorded. The primary endpoint of the study was survival to hospital discharge. Secondary endpoints were: (1) 30-day survival; and (2) progression to AVR. After BAV, all patients had postprocedural echocardiography, assessment for vascular complications including retroperitoneal hemorrhage, pseudoaneurysm formation, arterial dissection, and access-site major bleeding (Hb decrease ≥5 g/dL or bleeding requiring transfusion),¹⁶ and blood sampled for Hb concentration and eGFR. Periprocedural complications were recorded, including: (1) intraprocedural hypotension requiring intravenous vasopressors or intra-aortic balloon pump (IABP) insertion; (2) postprocedural bleeding requiring transfusion; (3) vascular complication associated with a reduction in Hb ≥5 g/dL and/or requiring surgery; (4) acute kidney injury, ie, decrease in eGFR ≥15% over baseline at 48 hours;¹⁷ and (5) cerebrovascular accident (CVA)/transient ischemic attack (TIA). Of those surviving to 30 days, blood was sampled for NT-proBNP.

Statistical analysis. Normally distributed data are reported as mean ± standard deviation and categorical variables as n (%). Student’s t-test was used to compare mean values for the continuous variables. The Chi-square or Fischer’s exact test was used to find significant associations between categorical variables. All tests were 2-tailed and P<.05 was considered statistically significant. The correlates with clinical, echocardiographic, and hemodynamic variables on both mortality and progression to AVR were studied with Cox proportional regression analysis. To determine independent correlates of 30-day mortality and progression to AVR, a stepwise multivariable Cox regression analysis was performed using those variables recorded in the clinical, echocardiographic, and hemodynamic categories with P<.05 on univariate analysis. Statistical analysis was performed using SPSS version 17.0 for Windows (SPSS Inc.).

Results

Between 01 August 2008 and 30 November 2010, 64 patients underwent isolated BAV at our institution. Baseline characteristics are summarized in Table 2. The study population was elderly (mean age, 82 ± 8 years) and predominantly female (55%), with symptomatic heart failure (56% NYHA class >II; NT-proBNP 11,195 ± 11,694 ng/L) and high operative risk (STS score, 13.7 ± 7.7; logistic EuroSCORE, 35.7 ± 19.5). At baseline, patients had LV ejection fraction (LVEF) of 42.9 ± 18.1%, aortic valve area (AVA) by continuity equation of 0.53 ± 0.17 cm², and transaortic peak gradient (PG) of 75.2 ± 25.3 mm Hg (Table 2). BAV was performed urgently or as an emergency in 22 patients (34%), with 9 of these having cardiogenic shock.

Indications for BAV are summarized in Figure 1. Initially, 44 patients (69%) had a treatment objective of symptom palliation (including those with cardiogenic shock) and 15 patients (23%) had a treatment objective of potential bridge to AVR. In addition, 5 patients (8%) received BAV to facilitate withdrawal of ventilation or non-cardiac surgery. At clinical reassessment within 1 month of BAV, 12 patients showed clinical improvement and underwent technical assessment for TAVI.  Following technical assessment, 5 patients were considered suitable for possible bridge to TAVI.

All patients had a retrograde transfemoral approach. Rapid pacing was used in 61 patients (95%). Catheterization laboratory door-to-balloon time was 31.1 ± 12.6 min. There was significant reduction in transaortic PG and significant increase in AVA on echocardiography (P<.001), with significant reduction in peak-to-peak gradient on catheterization (67.4 ± 19.5 mm Hg pre-BAV and 36.0 ± 16.5 mm Hg post-BAV; P<.001), following 1.3 ± 0.8 balloon inflations per patient. After the procedure, manual compression of the access site was applied in 53 patients (83%), with suture-mediated pre-closure in 11 patients (17%). Three patients (5%) required IABP insertion; however, these patients had severe concomitant coronary artery disease and had concurrent coronary PCI. No other forms of LV assist devices were used. Other clinical outcomes are summarized in Table 3. Of particular note, 1 patient (2%) suffered acute ischemic CVA, 4 patients (6%) had acute kidney injury though no patients required renal replacement therapy, and 5 patients (8%) had postprocedural bleeding requiring transfusion. All patients with postprocedural bleeding received manual compression of the access site.

Overall, 62 patients (97%) survived to hospital discharge (median duration of hospital admission, 4 days [2, 11 days]). Of those that did not survive to hospital discharge, both had cardiogenic shock, ie, systolic blood pressure (SBP) <90 mm Hg pre-BAV. In our study, the 30-day mortality rate was 13%. Patients who survived greater than 30-days postprocedure were more likely to be female, NYHA class ≤II, and have no greater than mild renal impairment at baseline. NT-proBNP had significantly improved at 30 days post-BAV (11,195 ± 11,694 ng/L pre-BAV vs 5,386 ± 11,554 ng/L 30 days post-BAV; P<.001). Preprocedure echocardiogram revealed higher LVEF (45.0 ± 17.7% vs 33.6 ± 17.3%; P<.001), higher transaortic PG (79.0 ± 26.2 mm Hg vs 62.4 ± 19.1 mm Hg; P<.05) and a lower proportion with greater than grade 2 aortic regurgitation [AR] (11% vs 37%; P<.001) in those who survived more than 30 days (n = 56). Of those who did not survive greater than 30 days post-BAV (n = 8), postprocedure echocardiography showed a significantly higher incidence of AR greater than grade 2 when compared to those who survived more than 30 days post-BAV (100% vs 37%; P<.001). Unsurprisingly, mortality was increased in those patients scheduled as either an urgent or emergency procedure and in those with higher rates of postprocedural complication, ie, AR greater than grade 2, acute kidney injury, and/or bleeding requiring transfusion. 

After multivariate adjustment, the strongest correlates for mortality pre-BAV were NYHA class >II (odds ratio [OR], 6.92; 95% confidence interval [CI], 0.723-54.48), SBP <90 mm Hg (OR, 19.04; 95% CI, 3.67-123.05), LVEF <45% (OR, 4.74; 95% CI, 1.26-34.29), transaortic PG <80 mm Hg (OR, 4.03; 95% CI, 1.27-13.43), and eGFR <45 mL min-1 (OR, 7.42; 95% CI, 2.79-30.89).

Overall, 8 patients (13%) receiving BAV progressed to AVR at median of 36 (33, 41) days. Of these, 3 patients received TAVI. In considering patients who bridged to SAVR (n = 5), 1 patient had an initial treatment objective of symptom palliation only, but showed clinical improvement within 1 month of BAV. The remaining 4 patients had an initial treatment objective of potential bridge to AVR, but were not technically suitable for TAVI following clinical improvement post BAV. Of those bridging to SAVR, 3 patients received coronary artery bypass grafting and 1 patient underwent mitral valve repair during the same procedure.

Patients who showed clinical improvement within 1 month of BAV (n =12) tended to be male, NHYA class ≤II, have lower transaortic PG as assessed by echocardiography both pre-BAV (71.4 ± 19.7 mm Hg vs 79.7 ± 24.3 mm Hg, respectively; P<.05) and post-BAV (61.8 ± 17.0 mm Hg vs 69.3 ± 18.9 mm Hg, respectively; P<.05) and have lower rates of significant comorbidity, irrespective of initial indication. No significant difference was detected in pre-BAV LVEF between those improving and those not improving post-BAV (44.1 ± 16.4% vs 45.5 ± 15.8%). Importantly, following clinical reassessment at 1 month, 12 patients declined further consideration for AVR due to personal reasons, including frailty, comorbidity, and satisfaction with the improvement achieved by BAV alone.

In patients showing clinical improvement, 5 patients were suitable for TAVI following technical assessment. Of these, 3 patients showed sufficient recovery of LV function and reduction in mitral regurgitation after BAV and bridged to TAVI (Figure 1). Interestingly, 1/3 (33%) of those receiving TAVI had an initial treatment objective of symptom palliation only. This patient successfully bridged to TAVI unexpectedly following resolution of heart failure and improved frailty after BAV.

After multivariate adjustment, the strongest correlates for AVR pre-BAV were NYHA ≤II (OR, 6.43; 95% CI, 1.11-42.87), eGFR ≥45 mL min-1 (OR, 4.78; 95% CI, 0.97-17.83) and transaortic PG <80 mm Hg (OR, 5.96; 95% CI, 1.72-35.43). Neither age nor gender were associated with 30-day mortality or progression to AVR in either the univariate or multivariate analyses.

Discussion

This study of our patients referred for BAV following the initiation of our TAVI program has found that: (1) in an elderly population with high operative risk, BAV has low 30-day mortality; (2) BAV improves echocardiographic and hemodynamic parameters of aortic obstruction favorably, which translates to a reduction in NT-proBNP at 30 days; (3) there exists a small cohort of patients who, although initially considered only suitable for symptom palliation, can proceed to AVR after BAV (Figure 1); (4) patients with high-risk clinical features can bridge to TAVI following BAV if they are technically suitable and show clinical improvement; and (5) clinical variables associated with mortality at 30 days post-BAV have been identified and may facilitate management decisions in these complex patients.

Despite initial enthusiasm for BAV in adults with calcific AS in the late 1980s, subsequent studies demonstrated that although there was initial symptomatic improvement,¹⁹ the procedure was associated with high complication and recurrence rates²⁰ and had little impact on long-term survival.²¹ In patients with severe symptomatic AS not eligible for SAVR, 1-year mortality is ≥44% despite maximal medical management and BAV.^3,8,22 AVR using TAVI has emerged as a viable treatment option in high-risk or inoperable patients.³ In our study, the STS scores and logistic EuroSCOREs were high (13.7 ± 7.7 and 35.7 ± 19.5, respectively), consistent with the clinical judgement that these were high-risk or inoperable patients.

Functional and hemodynamic statuses are generally accepted determinants of prognosis in patients with severe AS treated medically.^23,24 In the largest series of patients undergoing BAV, multivariate analysis demonstrated baseline functional status, baseline cardiac output, renal function, female gender, LV systolic function, and mitral regurgitation as predictors of mortality.²⁵ In addition, renal insufficiency correlates significantly with poor prognosis in patients undergoing SAVR.^8,26 Our results are congruent with these observations, ie, NYHA class >II, SBP < 90 mm Hg, LVEF <45%, and eGFR <45 mL min-1 were independent correlates of 30-day mortality. In this study, transaortic PG <80 mm Hg on echocardiography pre-BAV was also associated with adverse outcome at 30 days; however, this was due to poor LVEF in these patients. Moreover, these same variables with the exception of SBP <90 mm Hg were independent correlates of progression to AVR, whether TAVI or SAVR.

Some have interpreted the PARTNER trial as providing evidence that BAV as part of standard medical therapy for patients with severe AS does not alter the natural history of the disease, ie, 44.6% 1-year mortality from cardiovascular causes in those treated with conventional therapy including BAV.³ In this landmark study by Leon et al, a 20% improvement in 1-year survival was observed for patients treated with TAVI compared with patients who were treated with conventional therapy including BAV. These results herald a new era for the treatment of patients who otherwise would have been palliated. Over 1 year, only 5 patients would need to be treated with TAVI to prevent 1 death, and only 3 patients treated to prevent 1 death or repeat hospitalization.³

We believe our study demonstrates that there remains a role for BAV in the treatment algorithm for elderly high-risk patients with severe AS even in the TAVI era by improving symptoms, reducing aortic obstruction, and facilitating recovery of LV function in those with reduced LVEF but contractile reserve. In our study, of those with a treatment objective of either symptom palliation or potential bridge to AVR (n = 59), 12 patients showed clinical improvement within 30 days of BAV. Of these, 8 patients progressed to AVR (5 SAVR, 3 TAVI) (Figure 1) at a median 36 (33, 41) days after BAV and 4 patients refused AVR following satisfaction with the clinical improvement achieved by BAV only. Of particular note, 60% of those who showed clinical improvement following BAV and were technically suitable successfully bridged to TAVI, including 1 patient initially considered only suitable for symptom palliation. In addition, clinical and echocardiographic variables have emerged in this study that identify patients most likely to survive to 30 days and progress to AVR. Use of these variables may aid selection of those patients most likely to benefit from BAV.

Conclusion

BAV in isolation can improve symptoms;¹⁹ however, it has little impact on long-term survival in patients with severe symptomatic AS.²¹ TAVI has been shown to increase 1-year survival in patients with severe AS when compared to conventional therapy including BAV.³ In this study, BAV has shown potential in patients with symptomatic AS and high operative risk when utilized as a treatment option by a heart team that has an integrated approach including TAVI.

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From the Heart Centre, Royal Victoria Hospital, Grosvenor Road, Belfast, United Kingdom.
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. Financial support: Dr Michael J. Daly is supported by The Heart Trust Fund (Royal Victoria Hospital).
Manuscript submitted August 8, 2011, provisional acceptance given September 7, 2011, final version accepted November 22, 2011.
Address for correspondence: Dr M.J. Daly, Cardiology Research, West Wing, Royal Victoria Hospital, Grosvenor Road, Belfast United Kingdom. Email: michaeljdaly@hotmail.com