Outcomes of Patients Undergoing Balloon Aortic Valvuloplasty in the TAVI Era: A Multicenter Registry

Abstract: Background. Few clinical data about indications and prognoses of patients undergoing balloon aortic valvuloplasty (BAV) in the transcatheter aortic valve implantation (TAVI) era have been reported. Methods. Data from all consecutive patients undergoing BAV in seven European centers from 2006 to 2013 were collected. Acute results and long-term outcomes were assessed. Results. A total of 811 patients aged 82 ± 9 years were included; 416 patients (51%) underwent BAV as palliative destination therapy, 320 patients (40%) as bridge to TAVI, and 75 patients (9%) as bridge to surgical aortic valve replacement (SAVR). Patients undergoing BAV as destination therapy had a higher risk profile (logistic EuroSCORE, 20 ± 17 vs 22 ± 14 vs 11 ± 8, respectively; P<.001). Post procedure, peak gradient decreased from 87 ± 22 mm Hg to 66 ± 22 mm Hg (P<.001) and aortic valve area increased from 0.61 ± 0.2 cm² to 0.8 ± 0.2 cm² (P<.001). At 30 days, the all-cause death rate (6.5% vs 6.2% vs 7.4%, respectively; P=.56) and the rate of life-threatening and major bleedings (8.0% vs 5.7% vs 6.0%, respectively) did not differ between groups. After a mean follow-up of 318 days (range, 116-500 days), rates of all-cause death were similar (30% vs 34% vs 31%, respectively; P>.99), although patients undergoing BAV as bridge to SAVR showed a lower cardiovascular death rate (11% vs 11% vs 3%, respectively; P=.04). Conclusion. In the TAVI era, BAV may represent a reasonable option for patients with severe aortic stenosis and temporary contraindications to definite therapy. Given the mortality rates at 30 days, patients should be carefully selected, while events at follow-up are deeply influenced by the decision of whether or not subsequent interventions are performed. 

J INVASIVE CARDIOL 2015;27(12):547-553

Key words: balloon aortic valvuloplasty, TAVI, SAVR

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Patients with severe symptomatic aortic stenosis (AS) are exposed to a high risk of cardiovascular death and rehospitalization for heart failure if not treated with valve replacement.¹

Over the last years, the epidemiology of aortic valve disease has shifted from rheumatic to degenerative. This change, together with progressive aging in Western countries, has led to a population with a high number of comorbidities, and with a potentially high risk of operative mortality if treated with surgical aortic valve replacement (SAVR). Consequently, up to one-quarter of patients do not undergo SAVR despite clinical indications.¹

From the percutaneous intervention point of view, balloon aortic valvuloplasty (BAV) has been described as a potentially lower-risk strategy to treat patients deemed inoperable or at prohibitive risk for surgery. Despite initially promising results, the relatively high rate of procedural complications and low clinical benefit have confined BAV to patients presenting with cardiogenic shock, due to the quick re-increase of valvular gradients.²

The introduction of transcatheter aortic valve implantation (TAVI) has changed this scenario. This technique has been shown superior to medical therapy and at least not inferior to SAVR in AS patients at high risk,^3,4 and the inclusion of more complex patients has refueled interest in BAV. In some centers, BAV is routinely performed before TAVI; in others, it is only performed in select cases to clarify the impact of AS on symptoms, or to release symptoms as a bridge to TAVI/SAVR in patients with temporary contraindications to TAVI/SAVR, or as a destination therapy for palliative reasons.^5-7    

Encouraging BAV results have been described in the TAVI era,⁷ although they were limited by small sample size. Therefore, we performed a multicenter retrospective study to analyze baseline features, procedural and mid-term outcomes, and clinical management of patients with severe AS undergoing BAV.

Methods

The present study is reported in accordance with the Strobe Statement.⁸

Inclusion criteria. All consecutive patients with severe AS undergoing BAV were enrolled from the following institutions: Città della Salute e della Scienza, Turin, Italy; San Giovanni Bosco Hospital, Turin, Italy; Ferrarotto Hospital, Catania, Italy; Hospital Universitario MarquH. Marques de Valdecilla, Santander, Spain; Chest Hospital, London, United Kingdom; University Hospital, Toulouse, France; Brighton, United Kingdom; and St. Antonius Hospital, the Netherlands. Indication to BAV was evaluated by the Heart Team according to clinical guidelines and local clinical practice.⁹

Patient stratification. For the purposes of this analysis, patients were stratified according to indications for BAV: (1) pre-TAVI; (2) pre-SAVR; or (3) destination therapy, defined as patients without indications for TAVI or SAVR, according to recent guidelines and publications and to operator judgment.⁷ A sensitivity analysis was performed according to interventions after BAV (medical therapy, SAVR, or BAV).

Procedures. BAV procedures were performed with different devices (Balt Cristal, Nucleus, Numed, Tyshak, and Zmed II). The standard retrograde technique, through right and left femoral access or right humeral access, was exploited. A low-dose unfractionated heparin bolus was administered after sheath insertion in all patients (40-50 IU/kg). Rapid ventricular pacing was always exploited. The procedure was terminated based on one of the following criteria: three dilatations with complete pulse abrogation independent from hemodynamic results; balloon rupture or exchange and evidence of average gradient reduction of >50%; or acute severe aortic regurgitation. Access-site closure was performed either with safeguard after manual compression, surgically, or with a transcutaneous approach using Proglide, Proglide 2, Angio-Seal, or Prostar.

Data collection. Baseline clinical, symptomatic, and echocardiographic features were recorded retrospectively through electronic appraisal of medical records, as interventional features. Follow-up was performed through ambulatory visits or phone interview or formal query to primary physicians, by physicians performing the BAV procedures.

Study endpoints. The primary endpoint was the incidence of all-cause death. The combined secondary endpoint was the composite of cardiovascular death and rehospitalization due to heart failure, stroke, and myocardial infarction. All events were retrospectively adjudicated according to the Valve Academic Research Consortium (VARC) statement¹⁰ by at least two dedicated physicians, and divergences were resolved through consensus.

Statistical analysis. Continuous variables are expressed as mean ± standard deviation (SD) and were compared with ANOVA. Categorical variables are presented as counts and percentages and were compared with the chi-squared test. Statistical significance was set at the two-tailed .05 level. According to the number of events for variable appraised and for differences in follow-up,¹¹ Cox proportional hazard analyses were performed for all-cause mortality at long-term follow-up, including all variables significant at univariate analysis and for patients not undergoing surgical and percutaneous replacement. Computations were performed with SPSS version 22.0 (SPSS).

Results

A total of 811 patients were included from January 2006 to December 2013. Patients undergoing BAV as destination therapy represented the largest group (n = 416; 51.0%) followed by those evaluated for bridge to TAVI (n = 320; 40.0%) or to SAVR (n = 75; 9.0%). Overall, the mean age was 82 ± 9 years, 354 patients (43.6%) were male, 151 patients (18.6%) had previous myocardial infarction, and 61 patients (7.5%) had previous stroke. Mean creatinine clearance was 53 ± 5 mL/min and mean logistic EuroSCORE was 14 ± 13. Baseline characteristics of the population are shown in Table 1.

Patients undergoing BAV as a bridge to surgery reported a lower burden of comorbidities: they were younger, with lower rates of previous myocardial infarction and a preserved renal function, as summarized by higher levels of preoperative surgical risk score (STS score of 16 ± 14% vs 10 ± 8% vs 7 ± 8% [P<.001] and logistic EuroSCORE of 20 ± 17% vs 22 ± 14% vs 11 ± 8% [P=.01] for destination therapy, bridge to TAVI, and bridge to SAVR groups, respectively; Table 1).

Mean aortic valve area was 0.6 ± 0.2 cm² and mean peak gradient was 82 ± 29 mm Hg. Echocardiographic features did not vary among the groups; median ejection fraction was 49 ± 10%, 9% presented with mild aortic  regurgitation, and 7% presented with mitral regurgitation (Table 2).

In most cases (83.7%), one balloon was exploited. The Balt Crystal (52.4%), Zmed II (8.8%), and Tyshak II (15%) were the most frequently used balloons. The mean final balloon size was 22 ± 2 mm. The Proglide system for access closure was used in the majority of patients (70%).

At 30 days, no significant differences regarding outcomes were noted among the three groups. Rates of all-cause death (6.5% vs 6.2% vs 7.4%; P=.56) and cardiovascular death (4.9% vs 4.9% vs 2.9% P=.98) for destination therapy, bridge to TAVI, and bridge to SAVR groups, respectively, did not differ as those of major vascular and renal complications (Figure 1). 

Echocardiographic data were reported in-hospital for 75% of the patients. Peak gradient decreased from 87 ± 22 to 66 ± 22 mm Hg (P<.001), as did medium gradient (54 ± 17 mm Hg vs 41 ± 14 mm Hg; P<.001) and functional area (0.61 ± 0.2 cm² vs 0.8 ± 0.2 cm²; P<.001) (Figures 2 and 3).

At a median follow-up of 318 days (interquartile range, 116-500 days), rates of all-cause death were similar (30% vs 34% vs 31% for destination therapy, bridge to TAVI, and bridge to SAVR groups, respectively; P>.99), although patients undergoing BAV as bridge to SAVR showed lower rates of CV deaths (11% vs 11% vs 3% for destination therapy, bridge to TAVI, and bridge to SAVR groups, respectively; P=.04) (Figure 4). At multivariate analysis, clinical presentation with cardiogenic shock (odds ratio [OR], 6.5; 95% confidence interval [CI], 3-11) and renal clearance <60 mL/min/m² (OR, 2.1; 95% CI, 1.4-4) were the independent predictors of all-cause death (Figure 5).

Among patients undergoing BAV as bridge to SAVR, 6.6% underwent surgical intervention, 9.2% underwent TAVI, and 68.4% remained on medical therapy. Similarly, among patients undergoing BAV as bridge to TAVI, only 29.0% underwent percutaneous replacement, while 1.9% underwent SAVR and 65.1% remained on medical therapy. Finally, among patients undergoing BAV as destination therapy, 3.9% underwent surgical intervention while 14.5% underwent TAVI (Figures 6-9).

All-cause death rate was higher among patients who underwent redo BAV when compared with those who underwent TAVI/SAVR compared with those who had no intervention despite initial indication (17% vs 58% vs 36% vs 32%, respectively; P<.001) as rehospitalizations for heart failure (2% vs 35% vs 4% vs 2%, respectively; P<.001). 

Renal clearance <60 mL/min/m² (OR, 1.9; 95% CI, 1.4-4.5) and STS score (OR, 1.1; 95% CI, 1-1.6) were the independent predictors of not undergoing reintervention (both TAVI/SAVR) despite initial indications.

Discussion

The present study represents the largest sample size of patients undergoing BAV in the TAVI era. The main findings are: (1) bridge to TAVI or destination therapy were the most frequent clinical indications; (2) in high-volume centers, an acceptable rate of periprocedural complications has been recorded; (3) a significant reduction of aortic gradients was obtained post procedure; (4) at 1 year, most of these patients died for non-cardiac reasons, due to the great burden of comorbidities; (5) at 1 year, <30% of patients underwent TAVI/SAVR.

Bridge to TAVI or destination therapy represented the most frequent clinical indications for patients with severe AS with contraindications to definitive surgical or percutaneous replacement.^7,12 In a recent paper, Saia et al⁷ reported similar indications, especially due to the large number of comorbidities of these patients. Actually, chronic obstructive pulmonary disease and renal disease, which have been shown to exert a detrimental effect on prognosis,⁷ have been reported in up to 30% of these patients.

In patients with median STS values >10 and Logistic EuroSCOREs >15,¹⁹ 6.5% all-cause and 4% cardiovascular deaths occurred. These results are similar or even lower than those reported in other contemporary series^7,12 including patients presenting with cardiogenic shock. Vascular complications and bleedings occurred less often, for example, than in TAVI patients,^13,14 while again, the critical condition of the patients explain the rates of sepsis in this population.¹⁵ Moreover, stroke, one of the most feared complications of TAVI, occurred in only 1% of BAV patients.

Non-permanent reduction in aortic gradients has been seen as one of the most important limitations in this setting. We reported a decrease of 20 mm Hg in aortic peak gradients and 10 mm Hg in medium gradients, which was similar to the findings noted by Saia et al.⁷ This result may be very important because it describes the real reduction of valvular gradients, which is not a decrease toward values of transvalvular gradients typical of mild or moderate AS, but a stable reduction. It should be remembered, however, that even a small reduction in transvalvular gradient strictly relates to a decrease in telediastolic pressure and consequently in pulmonary pressure, with a strict relationship with symptoms.^16,17

This study demonstrates a mortality rate of 30% at the median follow-up of <1 year; this can be considered acceptable given the high-risk population, and is better than results obtained by past studies. However, there are relevant rates of non-cardiac death for patients undergoing BAV. This may be related to a selection bias wherein this population is excluded from a more definite solution due to the high number of comorbidities, with a deep impact on prognosis.

After 1 year, <30% of patients who underwent BAV as a bridge to surgical or percutaneous valve replacement had the procedure initially planned. Among these patients, all-cause death was significantly higher when compared with patients undergoing TAVI/SAVR, while cardiac death did not differ. Rehospitalizations for heart failure and all-cause death were much more frequent among patients undergoing redo BAV. Reduced renal function and higher STS score reduced the chance of undergoing definite interventions. These results are probably related to selection bias toward patients with a lower burden of comorbidities, and actually, those who did not undergo reintervention died mainly froms causes unrelated to the primitive cardiovascular disease.

Study limitations. Our study has many limitations, mainly related to its retrospective design, and to the evaluation of complications according to VARC definitions, which have been described and updated specifically for TAVI patients.

Conclusion

In the TAVI era, BAV may represent a reasonable option for patients with severe aortic stenosis and temporary contraindications to definite therapy. Due to the high-risk profile at baseline, early mortality rates are not much increased, while events at follow-up are deeply influenced by the decision of whether or not to perform subsequent interventions. 

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From the ¹Division of Cardiology, University of Turin, Città della Salute e della Scienza, Turin, Italy; ²Chest Hospital, London, United Kingdom; ³Toulouse University Hospital, Toulouse, France; ⁴Ferrarotto Hospital, University of Catania, Catania, Italy; ⁵Division of Cardiology, San Giovanni Bosco Hospital, Turin, Italy; ⁶Hospital Universitario MarquH, Marques de Valdecilla, Unidad de Hemodinamica y Cardiologia Intervencionista, Avda, Valdecilla, Santander, Spain; ⁷St. Antonius Hospital, CM Nieuwegein, the Netherlands; ⁸Sussex Cardiac Centre, Brighton, and Sussex University Hospitals, Brighton, Interventional Structural and Congenital Heart Disease, Brighton, United Kingdom; ⁹Translational Research, The Heart Research Institute, Sydney, Australia; ¹⁰Azienda Ospedaliera Policlinico Vittorio Emanuele, Catania, Italy; ¹¹Cardiology Department, Assuit University, Assuit, Egypt; and ¹²Division of Cardiology, La Sapienza, Rome, Italy.

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

Manuscript submitted June 1, 2015, provisional acceptance given July 6, 2015, final version accepted July 31, 2015.

Address for correspondence: Dr Salma Taha, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy; Cardiology Department, Assuit University Hospital, Assuit, Egypt. Email: esmaeil.salma@gmail.com; Website: www.cardiogroup.or