Abstract: Background. The introduction of transcatheter aortic valve replacement (TAVR) has renewed interest in balloon aortic valvuloplasty (BAV) for severe aortic stenosis (AS). It is unclear whether technical advances and increased operator experience associated with TAVR development have resulted in improved BAV outcomes. We performed a systematic review encompassing all published BAV studies and examined the evolution in indications, outcomes, and complications of BAV procedures since its inception. Methods. A literature search from 1986 through June 2013 was conducted for all studies reporting BAV outcomes. Studies with <50 BAV procedures were excluded. BAV outcomes and complications were compared in studies enrolling patients in the early/pre-TAVR and contemporary/TAVR periods (before vs after 2005). Results. Twenty-seven studies representing 4123 patients were included. In the contemporary era, BAV was performed as a bridge to TAVR in 23.4% of patients. Significant and comparable improvement in transaortic valvular gradients, aortic valve area, and cardiac output following BAV were observed in both time periods. There was, however, a significant reduction in procedural death (1.5% vs 2.9%; P<.01), in-hospital mortality (4.6% vs 8.5%; P<.001), and major vascular complications (4.0% vs 10.2%; P<.001) associated with BAV procedures in the contemporary/TAVR era. Conclusion. BAV is increasingly used as a bridge to TAVR, continues to impart significant hemodynamic improvement in patients with severe AS, and has an improved safety profile in the contemporary era.
J INVASIVE CARDIOL 2016;28(8):341-348.
Key words: aortic stenosis, balloon aortic valvuloplasty, meta-analysis, transaortic valve replacement, outcomes
Aortic stenosis (AS) is currently the most common valvular heart disease in the elderly, with a prevalence of moderate to severe AS in 2.8% of adults 75 years or older.1 Without treatment, AS is rapidly progressive with an average survival as low as 1-3 years after symptom onset.2-5 In the United States, only ~40% of patients with severe AS will undergo either surgical or transcatheter aortic valve replacement (TAVR).1 Surgical aortic valve replacement (SAVR) has been the gold-standard treatment for symptomatic patients for decades and is associated with low operative mortality in patients without significant comorbidities.6-10 In current clinical practice, many patients present with numerous medical comorbidities and advanced age, which make them prohibitive or high risk for SAVR.3 With an aging population, the prevalence of degenerative AS will continue to impose an increasing burden on the health-care system, requiring alternative forms of treatment for high-risk patients.11
Percutaneous balloon aortic valvuloplasty (BAV), first clinically introduced by Cribier in 1986, was initially proposed as a therapeutic option for non-operative patients with severe AS.12 Although immediate postprocedural hemodynamic parameters demonstrated modest but consistent improvement, high procedural mortality rate, high complication rate, and limited impact on long-term survival driven by temporary relief of the stenosis tempered the initial enthusiasm for the procedure.13-15 As a result, previous American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommended BAV as a possibly-reasonable therapy (class IIb) to be used as a bridge to surgery in hemodynamically unstable AS patients who are at high risk for SAVR, or for palliation in AS patients in whom AVR cannot be performed because of serious comorbidities.16
TAVR has emerged as a definitive therapy for patients with severe AS who are at prohibitive or high surgical risk.3,17-18 With the advent of TAVR, the development of novel devices, and technical improvements, a resurgence in the use of BAV has been observed. In the current report, we have performed a systematic literature review and pooled analyses of all published BAV studies aiming to examine changes in the indications, outcomes, and complications of BAV in the early/pre-TAVR and contemporary/TAVR eras.
Search strategy. Meta-analysis of observational studies in epidemiology (MOOSE) guidelines were largely followed.19 We searched Pubmed and the Cochrane Database of Systematic Reviews to identify all studies reporting stand-alone BAV outcomes published from the inception of BAV (1986) to June 20, 2013. Key words included “balloon aortic valvuloplasty,” “aortic balloon valvuloplasty,” “aortic valvuloplasty,” “aortic valvotomy,” “balloon aortic valvotomy,” and “aortic balloon valvotomy.” References from identified publications were additionally reviewed for inclusion. We excluded studies with <50 described BAV procedures, studies including data published in multiple reports (ie, double counting; in these cases, the most updated registry was incorporated in our analysis), studies performed in the pediatric population (age <18 years) or in animal models, studies describing the use of BAV exclusively in patients with rheumatic or bicuspid AS, studies describing the outcomes associated with BAV performed as part of another procedure (eg, TAVR), and studies published in non-English journals when translations were not available. After carefully screening all citations produced from the literature search and the aforementioned exclusions, a total of 27 published reports were identified. Access to 4 studies could not be obtained despite due diligence.
Data abstraction. Clinical and procedural data, including patients’ baseline characteristics, procedure indications (palliative, bridge to SAVR, bridge to TAVR, patient preference), procedure characteristics, hemodynamic outcomes (mean and peak transaortic valvular gradient [TAVG], aortic valve area [AVA], cardiac output [CO], systolic blood pressure [SBP]), procedural complications (death, major vascular complications as defined by the operator, myocardial infarction [MI], stroke, severe aortic insufficiency [AI], cardiac tamponade that occurred within 24 hours of procedure), and in-hospital mortality, were abstracted manually from the body texts, tables, and figures of the available published reports.
Statistical analyses. Descriptive analyses using cumulative weighted averages were computed and percentages and means ± standard deviations were reported for all variables and outcomes. These variables and outcomes were then compared between studies enrolling patients in the early/pre-TAVR and contemporary/TAVR periods, defined as before vs after January 2005, respectively. For studies that had enrollment periods in both the pre-TAVR and TAVR eras, they were categorized in the era in which the enrollment period was longer. Categorical variables were compared using the Chi-square test or Fisher’s exact tests, when appropriate, while continuous variables were analyzed using the Student’s t-test. Measures of heterogeneity, including Cochran’s Q-statistic and the I2 index tests, were computed using the random-effects model. A P-value ≤.05 was considered statistically significant. Statistical analyses were performed using STATA version 12 (STATA Corp).
The process of study selection and exclusion is outlined in Figure 1, with study characteristics and enrollment periods of each individual study described in Table 1 and Figure 2, respectively. In total, there were 27 published reports that met the inclusion and exclusion criteria for our analysis, of which 19 were case series and 8 were cohort studies. There were 24 single-center studies and 3 multicenter studies; 16 studies were performed in North America and 11 were performed in Europe.
The published reports included 4304 procedures performed in 4123 patients (Table 2). Baseline characteristics of patients in the systemic review reveal an elderly patient population (79.8 ± 9.5 years) with significant comorbidities (Table 2). The most common indications for BAV were excessive surgical risk (palliative; 76.7%), followed by bridge to TAVR (11.2%), bridge to SAVR (7.1%), and patient preference (5.0%). BAV was performed primarily through the retrograde approach (95.1%) using a single-balloon technique (92.6%) with rapid pacing predominantly a feature of the contemporary/TAVR era (84.9% vs 0.1%; P<.001).
Procedural hemodynamic measures demonstrated modest but consistent and statistically significant improvements in mean and peak TAVG, AVA, CO, and SBP (Table 3; Figure 4). Overall, procedural death was 2.2%, in-hospital mortality was 7.1%, and major vascular complications occurred in 7.0% of patients; small rates of severe AI, stroke, MI, and cardiac tamponade were observed (Table 3).
In the contemporary/TAVR era, patients undergoing BAV are more likely to be men (47.1% vs 43.0%; P=.01) and have a significantly higher risk profile, including a higher proportion of patients with congestive heart failure, hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, peripheral vascular disease, and chronic obstructive pulmonary disease, compared with patients undergoing BAV in the early/pre-TAVR era (Table 2). At the time of intervention, patients undergoing BAV in the contemporary/TAVR era were less likely to describe angina (10.5% vs 30.9%; P<.001) or syncope (12.9% vs 20.5%; P<.001); there was no significant difference in the presence of cardiogenic shock or New York Heart Association functional class IV congestive heart failure at time of intervention between the two groups. BAV continues to be used as a palliative measure in the contemporary era (65.6%), but is increasingly utilized as a bridge therapy to either TAVR or SAVR (23.4% and 11.0%, respectively) (Figure 3). Compared with outcomes in the early/pre-TAVR era, BAV outcomes improved markedly in the contemporary/TAVR era, with decreased procedural mortality (1.5% vs 2.9%; P<.01), in-hospital mortality (4.6% vs 8.5%; P<.001), and major vascular complications (4.0% vs 10.2%; P<.001) (Figures 5 and 6). For procedural mortality, there was significant heterogeneity among studies included in the early/pre-TAVR era (I2=52.1%; P=.01) and a non-significant trend for heterogeneity among studies included in the contemporary/TAVR era (I2=16.2%; P=.30). Similar rates of MI, stroke, severe AI, and cardiac tamponade were observed between the time periods.
To our knowledge, this is the first comprehensive report from the literature detailing the temporal trends in indications, outcomes, and complications of BAV. There has been a resurgence in the use of BAV with the advent and increased availability of TAVR that has markedly increased the number of patients with severe calcific AS who would ultimately benefit from valve replacement/implantation but who by virtue of various ongoing comorbidities, such as active decompensated heart failure or acute renal failure, are not immediately suitable candidates. As the utility of BAV expands to encompass more than a palliative role, particularly as a bridge therapy, it is important to further elucidate the safety profile of BAV in the contemporary/TAVR era.
Despite the expansion of BAV to patients who are overall sicker with more medical comorbidities in the contemporary era, BAV has lower procedural and in-hospital mortality and vascular complication rates, in spite of a greater incidence of peripheral vascular disease, compared with the previous decade. The reasons for this are likely multifactorial. In the early/pre-TAVR era, BAV was performed with the intent to cure and provide definitive treatment. Aggressive strategies, including multiple inflations and large-size balloons, were implemented. Once it became apparent that stand-alone BAV served predominantly as a palliative or bridge therapy, it was utilized instead as a temporizing measure and strategies became less aggressive. As the use of TAVR has progressively increased, operators have become more experienced with BAV given that it is incorporated as a component of the TAVR procedure (especially in transfemoral balloon-expandable TAVR procedures). This may be reflected by the demonstration of heterogeneity among trials included in the early/pre-TAVR era, possibly due to lack of operator experience and procedure standardization (eg, use of single-balloon vs double balloon techniques, retrograde vs antegrade approaches) prior to the advancement of TAVR. Interventional techniques and equipment have progressively improved since the inception of BAV both in terms of sheath sizes, balloon types (eg, the True Dilatation balloon valvuloplasty catheters by Bard Peripheral Vascular), and other procedural variables.20 Notably, the use of single-balloon as opposed to double-balloon techniques, and particularly the widespread adoption of the rapid burst-pacing technique (which allows for stable balloon positioning and reduces the risk of calcium embolization or aortic root damage) has become more prevalent in the contemporary/TAVR era.21-22 In addition, the use of suture-based vascular closure devices (eg, the preclosure technique) may have contributed to decreased access complications.23,24
Despite these improvements, however, BAV is still not considered a definitive therapy and is recognized to impart only modest improvements in hemodynamic measures. As noted in our report, BAV is increasingly used as a bridge procedure for patients undergoing TAVR or SAVR. Such patients may be acutely ill and need optimization with a temporizing BAV procedure before proceeding to definite valve replacement. Indeed, the 2014 ACC/AHA valvular guidelines note that percutaneous BAV may be considered as a bridge to SAVR or TAVR in patients with severe symptomatic AS (level of evidence C).24 Likely as a reflection of this evolving change in indication, BAV appears to be deployed earlier in the disease course in the contemporary/TAVR era, with fewer patients experiencing angina and syncope at the time of intervention compared with patients in the early/pre-TAVR era, who were more likely to undergo BAV as a palliative measure.
The goal of BAV as a bridge therapy is to transition the patient safely to undergo the procedure or surgery. Thus, operators should avoid overzealous BAV with large sizes and repetitive inflations, strive to avoid severe complications (eg, severe aortic insufficiency, aortic annulus rupture, major vascular complications), and be content with achieving modest reductions in the TAVG. Notably, the average time to SAVR/TAVR depends on competing factors. On the one hand, operators should allow enough time for patients to recover from the presenting clinical illness and its associated organ damage and regain, as much as possible, their functional capacity following the transient hemodynamic improvement imparted by BAV. On the other hand, the delay should be kept to a minimum to avoid valve restenosis. Overall, we prefer the average delay to SAVR/TAVR not to exceed 1-3 months following the BAV procedure.
Alternatively, some patients may have advanced comorbidities that may confound their clinical presentation and make it difficult to assess whether they would derive quality of life benefit from TAVR (eg, a patient with advanced chronic obstructive pulmonary disease and severe calcific aortic stenosis who presents with progressive dyspnea on exertion). In this instance, short-term improvement in symptoms following BAV helps ascertain the suitability of the patient for TAVR and rules out the “cohort C” patient with severe AS who is unlikely to derive much benefit from TAVR.
It is notable that our study excluded, due to double counting, the two largest studies of the early/pre-TAVR era describing BAV outcomes and complications.13,26 Immediate and long-term outcomes from these studies, among others, were paramount in demonstrating that patients have a very high mortality if they do not undergo post-BAV definitive therapies, such as TAVR or SAVR.13,26-27 For this reason, our report does not examine the long-term outcomes of BAV.
In summary, the current report provides a comprehensive review of the BAV literature and analyzes the hemodynamic, procedural, and clinical variables and outcomes of BAV, as well as the evolution of the procedure and its indications over time. The report therefore helps inform clinical practice about the improved safety of BAV in the contemporary era, and thus encourages its wider implementation in the proper clinical scenario.
Study limitations. This study is an aggregate analysis of retrospective data that is available via literature search. As such, it is limited by publication and reporting biases and lacks standardization of measures and outcome data. Additionally, outcomes were not risk adjusted given that we had no access to individual patient data.
BAV has become increasingly utilized in the contemporary/TAVR era. It is offered to patients with significantly more comorbidities and is more frequently adopted as a bridge to definitive AVR in patients considered too high risk or in whom the benefit of TAVR is uncertain. Modest but significant hemodynamic improvements following BAV are consistently observed; however, mortality and complication rates have significantly improved in the contemporary/TAVR era.
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From the 1Baylor College of Medicine, Houston, Texas; 2Michael E. DeBakey Veterans Affairs Hospital, Houston, Texas; 3Division of Cardiology, Duke University Medical Center, Durham, North Carolina; and 4Division of Cardiology, University of Washington, Seattle, Washington.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Paniagua is a founder and stockholder of the Colibri Heart Valve, LLC. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted December 30, 2015, provisional acceptance given February 16, 2016, final version accepted May 16, 2016.
Address for correspondence: Hani Jneid, MD, FACC, FAHA, FSCAI, The Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd, Cardiology 3C-320C, Houston TX 77030. Email: email@example.com