Abstract: Objectives. The study aim was to assess the effect of hourglass-shaped V8 and TAV8 balloons (InterValve, Inc) on aortic valve area (AVA) and other outcomes in patients with severe aortic stenosis undergoing balloon aortic valvuloplasty (BAV). BAV has re-emerged with transcatheter therapy. Cylindrical balloons have been the device of choice despite limitations. The hourglass-shaped balloons, with shorter, broader segments separated by a narrowed waist, permit enhanced fixation and better leaflet opening without annular or sinotubular compromise. Methods. We compared outcomes of InterValve balloon use in patients undergoing BAV with outcomes of cylindrical balloon use in patients from a BAV database. Patients were propensity matched by age, gender, baseline AVA, left ventricular ejection fraction, and Society of Thoracic Surgeons mortality risk score. Endpoints included change in AVA and aortic insufficiency (AI) by echocardiography, new permanent pacemaker (PPM) implantation, and major adverse events (ie, procedural death, emergency surgery, or stroke). Results. Forty InterValve balloon patients were matched with 40 cylindrical balloon patients. Postprocedure change in AVA trended strongly in favor of InterValve balloon patients (0.29 ± 0.17 cm2 vs 0.22 ± 0.15 cm2; P=.06). Maximum balloon sizes were significantly smaller for InterValve balloon patients. Worsened AI occurred less frequently with InterValve balloons. There was no difference in postprocedure PPM implantations or major adverse events. Conclusions. Use of the hourglass-shaped balloons provided larger AVA, as compared with use of cylindrical balloons. Use of the novel balloons was not associated with an increase in AI, PPM, or major adverse events.
J INVASIVE CARDIOL 2017;29(12):411-415.
Key words: new device, balloon aortic valvuloplasty
Initial experience with balloon aortic valvuloplasty (BAV) in the 1980s for the treatment of severe, calcific aortic stenosis as an alternative to surgical aortic valve replacement demonstrated technical feasibility, acceptable safety, and modest improvement in aortic valve area (AVA).1-4 Patients who underwent successful BAV experienced transient symptomatic improvement. With recognition of near-uniform restenosis in these patients, who were predominantly surgical candidates, enthusiasm for the procedure waned. Over the subsequent 10-15 years, non-surgical candidates – often elderly patients – were seldom offered the palliative benefits of this procedure.
Now that transcatheter aortic valve replacement (TAVR) has expanded the options for patients with aortic stenosis who are at high risk or are not surgical candidates, the use of BAV has undergone a resurgence. BAV is increasingly used as a bridge to TAVR. For example, “diagnostic” BAV is performed in patients with multiple causes for shortness of breath (eg, lung disease). BAV may be undertaken in patients with severe myocardial dysfunction, renal insufficiency, or other organ-system failure that may be reversible with this technique. BAV is also performed in high-risk patients for non-elective, non-cardiac surgery; in patients requiring high-risk percutaneous coronary intervention before TAVR (combined BAV and percutaneous coronary intervention); in hemodynamically unstable patients as a tool for TAVR predilation and postdilation; and for palliation in patients with limited longevity (ie, predicted survival less than 1-2 years).
Despite their limitations, cylindrical balloons have been the mainstay for BAV. However, “hourglass-shaped” valvuloplasty balloons (the V8 and its second-generation iteration, the TAV8 balloon; InterValve, Inc) have now been designed to better conform to the aortic valve anatomy, having proximal and distal bulbous segments separated by a persistently narrowed waist to permit enhanced fixation and broader leaflet opening without annular compromise. In this study of patients with severe aortic stenosis, we compare the effect of the InterValve balloons on AVA and other outcomes with those of patients who underwent BAV using traditional cylindrical balloons.
Study population and endpoints. Consecutive patients between January 2015 and December 2015 who underwent BAV with InterValve balloons for severe, symptomatic aortic stenosis at Abbott Northwestern Hospital in Minneapolis, Minnesota and United Hospital in Saint Paul, Minnesota were included in the present study. These patients were compared with a propensity-matched group on a 1:1 basis for age, gender, left ventricular ejection fraction (LVEF), baseline AVA, and Society of Thoracic Surgeons (STS) mortality risk score. The matched control group was selected from the Minneapolis Heart Institute Foundation’s prospective BAV database with 403 patients in whom cylindrical balloons were used. InterValve catheters are approved for commercial use by the United States Food and Drug Administration. All patients provided informed consent for their data to be collected for research purposes, and Institutional Review Board approval was obtained.
Endpoints included change in AVA and aortic insufficiency by echocardiography, new permanent pacemaker (PPM) implantation, and major adverse events. Intraprocedural hemodynamics were not used given the instability of acute postprocedural findings.5 Recorded major adverse events were defined as procedure-related mortality, major or minor stroke according to Valve Academic Research Consortium (VARC)-2 criteria, and the need for emergency surgery.6 Transthoracic echocardiographic images were obtained within 1 month preoperatively and within 72 hours postoperatively. Changes in AVA and degree of aortic insufficiency were documented from these echocardiographic studies. Aortic insufficiency was quantified numerically: 0 = none to trace; 1+ = mild; 2+ = moderate; 3+ = severe. For comparison, 12-lead electrocardiograms were recorded preoperatively and 24 hours postoperatively to determine the presence of new atrioventricular conduction defects.
The V8 and Second-Generation (TAV8) Balloons
The InterValve balloon is a geometrically shaped balloon that retains its hourglass shape throughout inflation (Figure 1), which permits the balloon to lock onto and conform to the unique aortic valve anatomy. The InterValve balloon proximal-bulb segment facilitates leaflet hyperextension into the aortic sinuses to yield a greater AVA post BAV. The balloon waist remains narrowed throughout the inflation-deflation cycle, which reduces the likelihood of annular dissection. The waist segment permits more aggressive incremental dilation using increased inflation volumes at more calcified or resistant leaflet bases. Compared with lengths of traditional valvuloplasty balloons (generally at least 40 mm), the shorter V8 balloon length of 32 mm and TAV8 balloon length of 24 mm reduce the likelihood of sinotubular ridge dissection or left ventricular trauma (Figure 2). The more rapid inflation-deflation times minimize the duration of systemic hypotension. Volume-driven inflations achieve predetermined precise waist and bulb segment diameters to minimize dissections.
The V8 balloon diagram and longitudinal dimensions are shown in Figure 3. The current balloon is made of Pebax, with a differential in the bulb and waist compliance characteristics. Current balloon sizes include 17, 19, 21, and 23 mm waist diameters; waist diameter was used to size the hourglass balloons given the convention of using the balloon-to-annulus ratio for selecting balloon sizes. With nominal inflations, the bulbs were 5 mm larger than the waist. Figure 3 demonstrates the different compliance characteristics of the waist and bulbous segment and precise volume-determined sizing.
Two patients underwent BAV with the second-generation (TAV8) balloon, which is also hourglass shaped. The TAV8 balloon is different from the V8 balloon only in longitudinal total and segment lengths. It has the advantage of being even shorter in total length than the V8 balloon (ie, 24 mm vs 32 mm). In addition, its distal segment is just 4 mm, limiting its potential for trauma in the left ventricular outflow tract (LVOT) and heart block, which are likely more common beyond this depth.
Procedural technique. BAV was performed using a previously described retrograde arterial technique.5 In both groups, valvuloplasty balloons were delivered and positioned across the aortic valve using Amplatz extra-stiff 0.035˝ exchange wires (Boston Scientific) delivered through 10-14 Fr femoral arterial sheaths. A broad loop was shaped in the distal guidewire for stable positioning in the left ventricle. Temporary balloon flotation, bipolar pacing leads were positioned in the right ventricular apex for rapid ventricular pacing at rates of 160-220 beats/min. Rapid ventricular pacing was performed to preserve balloon stability across the aortic valve during inflation. In the matched control group, 4 cm-long Z-Med and Z-Med II cylindrical balloons (B. Braun Interventional Systems) were used. These balloons were sized to achieve a 1.0:1.2 balloon-to-annulus ratio. Sequential inflations with larger balloons were performed if necessary in an attempt to achieve a 50% reduction in intraprocedural aortic valve mean gradient.
Recommended sizing strategy for the V8 and TAV8 balloons aimed to achieve a balloon waist-to-annulus ratio of 0.9:1.1. In the presence of moderate/severe LVOT calcification, use of the V8 balloons was avoided or markedly “under-sized.”
InterValve balloon positioning before inflation was performed by placing the mid radiopaque marker 1-2 mm distal to the annular calcium. If needed, progressively larger volumes were used to achieve greater waist diameter within the recommended limits of each balloon size. Rated burst pressure for this balloon is 3 atm. If needed, as with cylindrical balloons, a larger InterValve balloon could also be used. Approximately 80% of the V8 balloon inflations were performed with rapid ventricular pacing. Rapid ventricular pacing was left to the discretion of the operator and was often not used in the presence of marked left ventricular dysfunction. Successful balloon “locking” was achieved in more than 90% of patients not paced. The assistant operator performed rapid inflation, while the primary operator maintained a hold on the balloon catheter shaft and femoral artery sheath for “micro” adjustments in balloon position if necessary. Within the timeframe of this study, a cadaveric heart with aortic stenosis underwent ex vivo valvuloplasty with a 21 mm V8 balloon followed by macroscopic evaluation. The balloon waist diameter ratio was 1:1.5
Data analysis. Descriptive statistics are reported as mean ± standard deviation for continuous variables and as number and percentage for categorical variables. Categorical variables were analyzed with the Pearson Chi-square or Fisher’s exact tests, and continuous variables were analyzed with the Student’s t-test. A value of P<.05 was considered significant. All statistical calculations and plots were done with Stata version 11.2 (StataCorp).
Patient population and outcomes. All patients had severe calcific aortic stenosis and were either considered to be high risk for surgical aortic valve replacement or not operative candidates. TAVR was not used initially in these patients for a variety of reasons, including anticipated short longevity or hemodynamic instability in hopes of bridging. Forty consecutive patients underwent standalone BAV with the InterValve balloon for severe aortic stenosis. The first 38 patients underwent BAV with the V8 balloon, and the last 2 patients underwent BAV with the second-generation TAV8 balloon. This group was compared with 40 patients from the Minneapolis Heart Institute Foundation’s prospective BAV database of 403 patients in whom cylindrical balloons were used. The InterValve and cylindrical balloon groups were similar with respect to age, gender, LVEF, baseline AVA, and STS mortality risk score (Table 1). The echocardiographic baseline and postprocedure AVAs for the InterValve group were 0.73 ± 0.20 cm2 and 1.01 ± 0.28 cm2, respectively. The baseline and postprocedure AVAs for the cylindrical balloon group were 0.72 ± 0.09 cm2 and 0.94 ± 0.20 cm2, respectively. The echocardiographic increase in AVA from baseline to post procedure trended strongly in favor of the InterValve balloon group over the cylindrical balloon group (0.29 ± 0.17 cm2 vs 0.22 ± 0.15 cm2, respectively; P=.06) (Figure 4). The InterValve balloon waist segments were significantly smaller than the cylindrical balloon diameters because of the hourglass balloon shape. The InterValve balloon sizes ranged from 19-23 mm and the larger bulbs at the balloon ends ranged from 24-28 mm. The cylindrical balloon sizes ranged from 22-26 mm. The mean InterValve and cylindrical balloon sizes were 21.6 ± 1.4 mm vs 23.4 ± 1.67, respectively; P<.001). Worsened aortic insufficiency was more common in cylindrical balloon patients than in InterValve balloon patients (8 patients [20.0%] vs 3 patients [7.5%], respectively; P<.001) (Table 1). New, persistent, postprocedure high-grade atrioventricular block was present in 2 of the 80 patients, both with sinus rhythm and right bundle-branch block at baseline. One patient in each group thus required PPM implantation for a new high-grade atrioventricular conduction defect. No strokes or emergency surgeries were noted in either group, and procedural mortality occurred in 1 patient in the cylindrical balloon group secondary to annular rupture (Table 1).
Gross evaluation of the cadaveric heart with aortic stenosis demonstrated multiple calcified nodule fractures and splitting of one of the partially fused commissures. There were no leaflet tears or evidence of annular disruption (Figure 5).
Enhanced echocardiographically determined AVA was observed in favor of the InterValve balloon over standard cylindrical balloons (0.29 ± 0.17 cm2 vs 0.22 ± 0.15 cm2, respectively; P=.06). The more favorable improvement in predischarge echocardiographic AVA was seen in the absence of a morbidity or mortality “cost,” including comparisons for aortic insufficiency, which favored the hourglass-shaped balloon. The increase in AVA may be related to the larger balloon segment within the aortic sinus and hyperextension of the valve leaflets (Figure 6). The balloon size (waist) is smaller, resulting in a less “aggressive” balloon diameter-to-annulus ratio, possible accounting for fewer patients with worsened aortic insufficiency. The incidence of stroke, procedural mortality, PPM implantation, or emergency surgery was no different between the two groups. A previous study using Inoue balloons (Toray) via an antegrade, transseptal approach demonstrated similar benefits, albeit by intraprocedural catheterization hemodynamic comparison, and was considered to yield a greater gain in AVA, but in the absence of time for recoil to occur.7 While mechanistic conclusions drawn from gross findings of the single ex vivo heart with aortic stenosis following V8 valvuloplasty cannot be made, they are consistent with findings in previous studies.
The unique shape and compliance characteristics of the novel InterValve balloon offer enhancements gained by the larger proximal balloon segment and a narrowed waist that retains its narrow diameter throughout inflation. This design differentiates the V8 and TAV8 balloons from others, such as the Nucleus balloon (B. Braun Interventional Systems). The Nucleus balloon with full inflation is designed to ultimately take on the shape of a cylindrical balloon. However, the InterValve balloons, by preserving a narrower diameter at the waist than the larger proximal and distal ends, permit consistent locking on the aortic valve annulus both with and without rapid ventricular pacing. We believe that the shorter TAV8 balloon (24 mm), with its 4 mm-long LVOT segment, will reduce the likelihood of LVOT trauma and atrioventricular block while preserving all the functionality of the V8 balloon. In the absence of strongly moderate or severe calcification in the LVOT segment in all the study patients, we identified no morbidity or major adverse events in the 38 V8 balloon patients and 2 TAV8 balloon patients. Conclusions cannot be drawn from the 2 TAV8 patients in this series. The differential compliance of the balloon segments (waist > ends) permits a strategy of serial dilation with increasing balloon volumes (increasing waist diameter) using a single balloon to achieve targeted improvement in aortic valve flexibility at the calcified leaflet bases. If necessary, a larger balloon size can be used to achieve a greater degree of leaflet hyperextension without oversizing the balloon waist with regard to the annulus. Precise diameters in the respective balloon segments are achieved with specified inflation volumes.
Study limitations. Limitations of this study include its small size and its non-randomized nature. We attempted to minimize bias by selecting consecutive patients in the InterValve balloon group and using a 1:1 propensity-matched comparison with patients who had undergone BAV with cylindrical balloons from a 403-patient BAV database. Preoperative and postoperative echocardiography (rather than intraprocedural catheterization hemodynamics) was used given our previous findings of more consistent and stable postprocedural AVA as assessed by predischarge echocardiography.5
Use of the V8 and TAV8 InterValve hourglass-shaped valvuloplasty balloons in patients with calcific aortic stenosis was associated with decreased incidence of worsened aortic insufficiency. There were no differences between groups in new PPM or occurrence of major adverse events. Use of the hourglass-shaped balloon trended toward a larger post BAV increase in AVA when compared with the cylindrical balloon.
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From the 1Twin Cities Heart Foundation, Minneapolis, Minnesota; 2Midwest Academy for Gifted Homeschooled Students, Maryland Heights, Missouri; 3Center for Valve and Structural Heart Disease, Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota; 4VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, Texas; and 5United Heart and Vascular Clinic, Saint Paul, Minnesota.
Funding: This study was funded, in part, by InterValve, Inc. Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Pedersen and Dr Sorajja are co-founders of InterValve, Inc; they report ownership of equities, personal fees, and patents (Dr Pedersen only) from InterValve, Inc. Dr Brilakis reports personal fees from Abbott Vascular, Asahi Intecc, Elsevier, GE Healthcare, and Cardinal Health; grants from Boston Scientific and InfraRedx; spouse is an employee of Medtronic. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted April 10, 2017, provisional acceptance given April 17, 2017, final version accepted May 5, 2017.
Address for correspondence: Dr Wesley Pedersen, Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, 800 East 28th Street, Minneapolis, MN 55407. Email: Wesley.Pedersen@allina.com