1188
`
`JACC Vol. 17, No.5
`April 1991:1188-95
`
`SEMINAR ON BALLOON AORTIC VALVULOPLASTY-V
`
`William W. O'Neill, MD, FACC, Guest Editor
`
`Follow-Up Recatheterization After Balloon Aortic Valvuloplasty
`
`THOMAS M. BASHORE, MD, FACC, CHARLES J. DAVIDSON, MD, FACC AND THE MANSFIELD
`SCIENTIFIC AORTIC VALVULOPLASTY REGISTRY INVESTIGATORS
`
`Durham, North Carolina
`
`The results of recatheterization were assessed in a select group of
`95 patients enrolled in the Mansfield Scientific Aortic Valvulo(cid:173)
`plasty Registry to determine whether any procedural or patient(cid:173)
`related variables at baseline predicted either initial immediate or
`follow-up (6.2 ± 3.3 months) results. At the follow-up catheter(cid:173)
`ization, 39 (41 %) of the patients were in improved condition and
`56 patients (59%) had recurrence of symptoms, allowing for
`analysis of the effect of the procedure in two symptomatic patient
`subsets.
`In the total group the aortic valve area increased initially from
`0.56 ± 0.16 to 0.87 ± 0.27 cm2 but partial return to the baseline
`
`valve area was evident at follow-up (0.63 ± 0.25 cm2). Similarly,
`the mean aortic gradient initially decreased from 72 ± 30 to 35 ±
`16 mm Hg but then increased to 55 ± 25 mm Hg at follow-up.
`Neither the initial nor the late hemodynamic results appeared
`affected by any definable procedural variable at the time of
`valvuloplasty, including the maximal diameter of balloons, num(cid:173)
`ber of balloons simultaneously used, mean inflation time or total
`number of inflations.
`
`Such technical concerns also did not seem to affect short- or
`long-term outcome. Similarly, no baseline hemodynamic variable
`clearly separated those who became increasingly symptomatic
`from those whose condition was improved at the 6 month interval.
`At recatheterization, a reduction in the aortic valve area toward
`baseline was observed in 24 (62 % ) of the 39 improved patients and
`in 45 (80%) of the 56 who were symptomatic. At follow-up the less
`symptomatic group did have a greater aortic valve area
`; p = 0.02) and a slightly
`(0.70 ± 0.32 versus 0.58 ± 0.18 cm2
`higher ejection fraction (59 ± 19% versus 48 ± 20%; P = 0.07)
`than the symptomatic group.
`Thus, in this select group of patients, differences in procedural
`techniques at the time of aortic valvuloplasty did not appear to
`influence the return toward the baseline aortic valve gradient at
`follow-up. Fewer symptoms at follow-up were observed in those
`patients achieving the greatest aortic valve area after the proce(cid:173)
`dure and in those with maintenance of left ventricular contractile
`performance.
`
`(J Am Coli CardioI1991;17:1188-95)
`
`Percutaneous balloon aortic valvuloplasty has emerged as a
`therapeutic option in selected patients with severe aortic
`stenosis who are poor candidates for surgery (1-5). How(cid:173)
`ever, clinical studies (2,6,7) have revealed that evidence for
`restenosis, with or without return of clinical symptoms,
`occurs frequently. The acute relief of aortic obstruction
`observed using balloon catheter techniques appears to result
`from fracture of valvular calcium, tearing of commissural
`scar and perhaps stretching of the cusps or the aortic anulus
`(8-13). In the early days after the procedure, partial return of
`a pressure gradient occurs because of both remodeling of the
`aortic valve and an improvement in stroke volume (14,15).
`Restenosis may be an inevitable consequence at some point,
`
`Manuscript received September 10, 1990; revised manuscript received
`October 6, 1990, accepted October 24, 1990. Parts I through IV of this
`Seminar appeared in the January, February, March 1 and March 15, 1991
`issues of the Journal (Vol 17, pages 187-98.485-91. 828-33 and 909-13).
`Address for reprints: Thomas M. Bashore. MD, Cardiovascular Labora(cid:173)
`tory, Box 3012, Duke Medical Center. Durham. North Carolina 27710.
`
`after the procedure, although the mechanism of restenosis
`has yet to be well defined and its definition is controversial
`especially in light of the vagaries in the measurement of
`aortic valve area. It remains unclear, for example, which
`factors, such as valve architecture (12), underlying ventric(cid:173)
`ular function (16-18) or variations in the procedure itself
`(19-23), might be most important in delaying restenosis or
`the return of symptoms. Preliminary studies (3) have sug(cid:173)
`gested that the final aortic valve area probably best predicts
`early restenosis, and it has been advocated that a final aortic
`valve area> 1.0 cm2 after valvuloplasty should always be
`sought.
`To date, follow-up data in patients after aortic valvulo(cid:173)
`plasty have primarily used noninvasive methods, such as
`Doppler echocardiography, to estimate the severity of the
`valvular gradient or to measure aortic valve area. Although
`Doppler gradients correlate reasonably well with invasive
`measures, substantial standard errors for the measurement
`of the mean aortic gradient and of the aortic valve area using
`the continuity equation have been described (24). For these
`
`©1991 by the American College of Cardiology
`
`0735-1097/91/$3.50
`
`Downloaded From: http://content.onlinejacc.org/ on 12/07/2015
`
`Edwards Exhibit 1030, pg. 1
`
`

`
`JACC Vol. 17, No, 5
`April 1991:1188-95
`
`BASHORE ET AL.
`RECATHETERIZA TION AFTER AORTIC VALVULOPLASTY
`
`1189
`
`reasons, follow-up invasive data are important to allow for
`comparison of serial hemodynamic changes with use of
`similar techniques.
`Analysis of data in the Mansfield Scientific Aortic Valvu(cid:173)
`loplasty Registry from December I, 1986 to September I,
`1988 reveals that 95 patients underwent repeat catheteriza(cid:173)
`tion after aortic valvuloplasty. This time interval is greater
`than that reported elsewhere in this seminar. Both patient
`characteristics and details of the technique at the time of the
`initial procedure were available for review. This presenta(cid:173)
`tion is an assessment of the effect of these variables on the
`subsequent follow-up invasive hemodynamic outcome In
`these patients.
`
`Methods
`The Mansfield Scientific Aortic Valvuloplasty Registry.
`The Registry is a corporate-sponsored data base established
`through Mansfield Scientific and conducted under Food and
`Drug Administration-approved investigation device exemp(cid:173)
`tion. Clinical sites were required to complete a questionnaire
`regarding a series of procedural events, hemodynamic re(cid:173)
`sults and complications in all patients undergoing aortic
`valvuloplasty using balloon valvuloplasty catheters designed
`by the parent company. In addition to clinical follow-up,
`data from repeat catheterization were also sought.
`During this time, 785 patients were enrolled in the Reg(cid:173)
`istry. At the time of this report, 525 patients were both alive
`and eligible for a 6 month follow-up catheterization. Fol(cid:173)
`low-up catheterization was not a routine requirement; there(cid:173)
`fore, many patients underwent recatheterization because of
`recurrence of symptoms. In some centers recatheterization
`was incorporated into an institutionally approved protocol
`for the evaluation of the aortic valvuloplasty procedure.
`Therefore, the Registry included a mixed group of patients
`who had undergone repeat catheterization. Of the 525 eligi(cid:173)
`ble patients, 95 (18%) underwent recatheterization and these
`patients form the basis of this report.
`An aortic valvuloplasty data base form allowed recording
`of information regarding the valvuloplasty procedure, as
`well as pertinent hemodynamic data and clinical symptoms.
`The procedural data base included the number of balloons
`used, the maximal diameter of each balloon, the balloon
`length, the number of inflations, the duration of each infla(cid:173)
`tion and information on whether balloon rupture occurred
`and whether any complications ensued.
`A baseline data base was also derived regarding the
`symptomatic status of each patient. This included documen(cid:173)
`tation of fatigue, shortness of breath, angina, syncope,
`congestive heart failure class (New York Heart Association)
`and angina class (Canadian Cardiovascular Society). The
`overall clinical status was also recorded as stable, improving
`or worsening.
`Recatheterization data were tabulated in a manner sim(cid:173)
`ilar to that recorded at baseline. Recatheterization was
`performed at an average of 6.2 ± 3.3 months after the
`
`baseline procedure. At recatheterization 42 patients (44%)
`underwent repeat aortic valvuloplasty. Another five patients
`had repeat valvuloplasty during the same readmission. Thir(cid:173)
`teen patients (14%) underwent aortic valve replacement
`during the follow-up hospital admission and seven patients
`(7%) died during that hospital stay.
`Patient characteristics. Table 1 outlines pertinent base(cid:173)
`line clinical descriptors before valvuloplasty in the 95 pa(cid:173)
`tients who underwent recatheterization and contrasts them
`with descriptors in the subgroup of patients who did not
`undergo repeat catheterization. The two groups had similar
`baseline characteristics except for slightly more coronary
`artery disease and slightly less congestive heart failure in the
`study cohort. At 6 months more symptoms were present in
`the recatheterization group. Because 30% of patients died
`before they were eligible for recatheterization, the signifi(cid:173)
`cance of this observation is unclear except that it confirms
`the view that many patients were restudied because symp(cid:173)
`toms were present. Because all descriptors were not re(cid:173)
`corded for all data items, Table 1 includes the actual number
`of patients from whom the data were derived for each
`variable. Overall, the patient group is elderly with mild to
`moderate coronary artery disease, moderately well pre(cid:173)
`served ventricular function and a modest degree of aortic
`regurgitation.
`Table 2 outlines the symptomatic status of the 95 patients
`at baseline and at the time of the repeat study. Symptomatic
`improvement at recatheterization was evident in regard to
`heart failure classification, syncope and angina. However,
`the overall number of patients with any symptom of fatigue
`or dyspnea was unchanged. At the time of recatheterization,
`the condition of 39 (41 %) was considered improved, whereas
`56 (59%) had either similar or worse symptoms compared
`with baseline.
`Statistical analysis. Data were expressed as the mean
`values ± SD or as mean values and the 95% confidence
`limits for the mean. Statistical analysis between groups was
`performed using either a paired or unpaired t test for
`continuous data and Fisher's exact test for dichotomous
`variables. A p value < 0.05 was considered significant.
`
`Results
`Initial and follow-up hemodynamic changes observed.
`Table 3 outlines the initial hemodynamic changes observed
`in the patients at the time of their original aortic valvulo(cid:173)
`plasty procedure and contrasts the data with data observed
`at follow-up catheterization. Ejection fraction values ob(cid:173)
`tained immediately after the procedure were not recorded on
`the data sheets and were not available for review.
`Figure 1 displays the immediate effects of aortic valvulo(cid:173)
`plasty on the aortic valve area and contrasts these initial
`measurements with values observed at follow-up catheter(cid:173)
`ization. It is obvious that a return toward the baseline
`gradient and aortic valve area was common. When patients
`with fewer symptoms were compared with those whose
`
`Downloaded From: http://content.onlinejacc.org/ on 12/07/2015
`
`Edwards Exhibit 1030, pg. 2
`
`

`
`1190
`
`BASHORE ET AL.
`RECA THETERIZA TION AFTER AORTIC VALVULOPLASTY
`
`JACC Vol. 17, No.5
`April 1991: 1188-95
`
`Table 1. Comparison of Patients Undergoing Recatheterization With Patients Who Had No Recatheterization Performed
`
`Recatheterization
`
`No Recatheterization
`
`Baseline characteristic
`Male(%)
`Age (yr)
`CHF
`NYHA I or II
`NYHA III or IV
`Fatigue
`Dyspnea
`Angina
`Syncope
`Aortic regurgitation
`o to mild
`Moderate to severe
`CAD
`None or IVD
`2VD or 3VD
`Prevalvuloplasty Hemodynamics
`AVA (cm2)
`Peak to peak aortic gradient (mm Hg)
`L VEDP (mm Hg)
`LVEF(%)
`Postvalvuloplasty Hemodynamics
`AVA (cm2)
`Mean aortic pressure gradient (mm Hg)
`Follow-up symptoms
`Mean FlU time (mo.)
`CHF
`NYHA I or II
`NYHA III or IV
`Fatigue
`Dyspnea
`Angina
`Syncope
`Improved (%)
`
`No.(%)
`
`47 (49%)
`75 ± 10
`51 (54%)
`23 (24%)
`68 (71%)
`56 (59%)
`83 (87%)
`53 (56%)
`22 (23%)
`
`57 (85%)
`10 (15%)
`
`70 (74%)
`19 (26%)
`
`0.56 ± 0.16
`72 ± 30
`19 ± 11
`49 ± 20
`
`0.87 ± 0.27
`35 ± 16
`
`6.2
`47 (49%)
`35 (37%)
`54 (57%)
`58 (61%)
`68 (71%)
`31 (33%)
`II (12%)
`39 (41%)
`
`n
`
`95
`95
`95
`91
`91
`95
`95
`95
`95
`
`67
`67
`
`89
`89
`
`95
`95
`95
`65
`
`95
`95
`
`95
`95
`95
`95
`95
`95
`95
`95
`95
`
`No(%)
`
`310 (45%)
`78 ± 5
`296 (68%)
`84 (19%)
`360 (81%)
`317 (71%)
`431 (91%)
`239 (51%)
`113 (25%)
`
`380 (88%)
`53 (12%)
`
`424 (76%)
`136 (24%)
`
`0.50 ± 0.18
`60 ± 23
`19 ± 14
`49 ± 19
`
`0.82 ± OJI
`30 ± 13
`
`6.7
`102 (34%)
`241 (62%)
`145 (38%)
`147 (49%)
`185 (60%)
`63 (21%)
`20 (7%)
`21\ (65%)
`
`n
`
`690
`690
`435
`444
`444
`445
`472
`469
`455
`
`433
`433
`
`560
`560
`
`684
`690
`670
`316
`
`673
`678
`
`443
`298
`386
`386
`303
`307
`303
`293
`325
`
`p Value
`
`NS
`<0.001
`<0.01
`NS
`NS
`<0.05
`NS
`NS
`NS
`
`NS
`NS
`
`NS
`NS
`
`<0.01
`<0.001
`NS
`NS
`
`NS
`<0.001
`
`NS
`<0.01
`<0.0005
`<0.005
`<0.05
`<0.05
`<0.025
`NS
`<0.0005
`
`The baseline characteristics, hemodynamic values before and immediately after valvuloplasty and the symptoms at the follow-up (FlU) interval are displayed
`for those who had, compared with those who had not, undergone recatheterization. There are no differences noted in any baseline characteristic except for a slight
`increase in fatigue and congestive heart failure (CHF) in the subsets not undergoing recatheterization. No hemodynamic measurement differed between the two
`groups. At follow-up the recatheterization group of patients had more symptoms in all categories and were generally less improved. This suggests that in the
`majority of patients recatheterization was performed because of symptoms. AVA = aortic valve area; CAD = coronary artery disease; LVEDP = left ventricular
`end-diastolic pressure; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; VD = vessel disease.
`
`symptoms had returned to baseline severity, there was no
`difference in any measurable baseline hemodynamic varia(cid:173)
`bles. Similarly, when the immediate results of the valvulo(cid:173)
`plasty were assessed, there was no acute postprocedural
`hemodynamic variable seen more commonly in the patients
`with improved status than in those with recurrent symptoms
`(Table 4).
`At follow-up catheterization, many patients with im(cid:173)
`provement demonstrated evidence for a return of the valve
`gradient. The follow-up aortic valve area was larger in
`patients who were clinically improved at 6 months. These
`patients also had a higher ejection fraction and had experi(cid:173)
`enced a greater change in the ejection fraction from baseline
`(from 50 ± 21% to 59 ± 19%) compared with that in patients
`whose symptoms had worsened or returned to baseline
`
`Table 2. Symptomatic Status of Patients
`Undergoing Recatheterization
`
`Congestive heart failure
`Fatigue
`Dyspnea
`NYHA I or II
`NYHA III or IV
`Angina
`Syncope
`
`At
`Baseline
`
`51 (54%)
`56 (59%)
`83 (87%)
`23 (24%)
`68 (71%)
`53 (53%)
`22 (23%)
`
`At 6 Month
`Recatheterization
`
`p Value
`
`47 (49%)
`58 (61%)
`68 (71%)
`35 (37%)
`54 (57%)
`31 (33%)
`II (12%)
`
`NS
`NS
`NS
`<0.05
`<0.05
`<0.05
`<0.05
`
`The change in symptomatic status in patients undergoing recatheterization
`is redisplayed from Table I. At recatheterization a reduction in anginal and
`syncopal symptoms was noted but there was no change in overall symptoms
`of heart failure in this select subset. More patients reported functional class I
`or II symptoms at follow-up than at baseline.
`
`Downloaded From: http://content.onlinejacc.org/ on 12/07/2015
`
`Edwards Exhibit 1030, pg. 3
`
`

`
`JACC Vol. 17, No.5
`April 1991:1188-95
`
`Table 3. Hemodynamic Data
`
`Aortic valve area (cm2)
`Mean aortic gradient (mm Hg)
`Peak to peak aortic gradient (mm Hg)
`LVEF(%)
`L VEDP (mm Hg)
`
`BASHORE ET AL.
`RECATHETERIZATION AFTER AORTIC VALVULOPLASTY
`
`1191
`
`Baseline
`Before BAV
`
`0.56 :!: 0.18
`72 :!: 30
`59:!: 21
`49 :!: 20
`19:!: 11
`
`n
`
`95
`95
`95
`65
`95
`
`Immediately
`After BAV
`
`0.87:!: 0.27
`35 :!: 16
`32:!: 12
`NA
`16:!: 9
`
`n
`
`95
`95
`95
`
`94
`
`At Follow-Up
`Catheterization
`
`0.63 :!: 0.25
`55:!: 25
`51 :!: 21
`53 :!: 21
`19:!: \0
`
`n
`
`92
`94
`94
`48
`95
`
`Baseline, immediate postvalvuloplasty and follow-up catheterization hemodynamic data in 95 patients. The initially improved hemodynamic values observed
`after balloon aortic valvuloplasty (BAV) have returned toward baseline in many patients. Abbreviations as in Table 1.
`
`levels. This finding may have clinical relevance because it
`appears symptoms may not recur despite evidence for a
`return toward baseline of the aortic valve area and gradient
`in some patients.
`Analysis of the procedural events and their impact on
`outcome. Several valvuloplasty technique variables were
`assessed to determine their relation to either the immediate
`or at 6 month follow-up catheterization outcome. Figure 2
`displays the effect of maximal balloon size (diameter) on the
`change in aorta valve area observed, the aortic valve area
`after the valvuloplasty procedure and the aortic valve area at
`recatheterization. Although there is a slight trend toward a
`larger resultant aortic valve area at recatheterization when
`larger balloons were used initially, in general the use of a larger
`balloon size did not seem to correlate with a better valve area
`at restudy. The number of patients for whom each balloon size
`
`Figure 1. Aortic valve area data in 95 patients. Left panel, the effect
`of balloon aortic valvuloplasty on the aortic valve area (A V A)
`immediately after the procedure. Note the upward shift in data
`points. Right panel, at recatheterization the aortic valve area has
`returned to baseline in many patients, although there are still more
`patients above the line of identity than below it. Individual dots often
`represent more than one patient.
`
`was used is recorded at the bottom of the figure and it is
`important to note that the overwhelming majority of patients
`had either a single 20 mm balloon (63%) or a combination of
`balloons with a total summed diameter of 30 mm 01%).
`Because of the small number of patients with balloons of other
`sizes, it is difficult to discern the true effect of balloon size,
`other than that of the two most commonly used.
`The effect of the total number of balloon inflations on aortic
`valve area either immediately after the procedure or at recath(cid:173)
`eterization is shown in Figure 3. Again, the number of inflations
`appears to be unrelated to outcome; from two to six inflations
`were performed in most instances. On the assumption that the
`duration of each inflation may playa role, the hemodynamic
`status immediately after the procedure was assessed relative to
`inflation time. However, Figure 4 reveals no obvious relation
`between inflation time and aortic valve area. Similar findings
`were obtained for all hemodynamic variables. The majority of
`inflations lasted :0:;30 s.
`When these same technical variables were reassessed in
`the symptomatic subsets at 6 month follow-up study, no
`relation between any technical event and symptomatic out(cid:173)
`come was found. For instance, the largest diameter balloon
`or balloons in the patients with symptomatic improvement
`
`2.0
`
`1.8
`
`1.6
`
`1.0
`
`N
`E 1.4
`U
`......
`< 1.2
`> <
`f-
`en
`0 0.8
`0-
`W
`f- 0.6
`::::l
`()
`< 0.4
`
`2.0
`
`1.8
`
`1.6
`
`1.0
`
`1.4
`N
`E
`...... 1.2
`U
`:c
`I-
`< ()
`I
`W 0.8
`c:
`< 0.6
`> <
`
`0.4
`
`0.2
`
`0 0
`
`n = 95
`
`0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
`AVA BASELINE (cm 2 )
`
`•
`
`• •
`
`n = 95
`
`• • •
`•
`
`•
`
`•
`
`0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
`AVA BASELINE (cm 2 )
`
`Downloaded From: http://content.onlinejacc.org/ on 12/07/2015
`
`Edwards Exhibit 1030, pg. 4
`
`

`
`1192
`
`BASHORE ET AL.
`RECATHETERIZA TION AFTER AORTIC VALVULOPLASTY
`
`lACC Vol. 17, No.5
`April 1991:1188-95
`
`Table 4. Comparative Analysis of 39 Patients Symptomatically Improved Versus Those 56 With
`Similar or Worse Symptoms at the 6 Month Follow-up Catheterization
`Improved Compared
`Similar or Worse
`With Baseline
`Compared With Baseline
`(n = 39)
`(n = 56)
`
`P
`
`AVA (cm2
`)
`Baseline
`Acute post
`Follow-up
`Mean aortic gradient (mm Hg)
`Baseline
`Acute post
`Follow-up
`Ejection fraction (%)
`Baseline
`Follow-up
`L VEDP (mm Hg)
`Baseline
`Acute post
`Follow-up
`
`0.57 ± 0.19
`0.91 ± 0.29
`0.70 ± 0.32
`
`62 ± 21
`32 ± II
`50 ± 20
`
`50 ± 21
`59 ± 19
`
`21 ± 14
`16 ± 9
`20 ± 11
`
`0.56 ± 0.18
`0.85 ± 0.24
`0.58 ± 0.18
`
`57 ± 20
`31 ± 18
`52 ± 22
`
`47 ± 20
`48 ± 20
`
`19 ± 12
`17 ± 8
`18 ± 9
`
`0.71
`0.32
`0.02
`
`0.20
`0.47
`0.72
`
`0.58
`0.07
`
`0.42
`0.76
`0.44
`
`At follow-up catheterization, the aortic valve area (A V A) was greater and the ejection fraction marginally higher
`in the group of patients with clinical improvement. No other identifiable variable was found that was more common
`in the improved subset. Abbreviations as in Table I.
`
`was 23 ± 6 mm versus 23 ± 6 mm in those with recurrent
`symptoms. Likewise, the average inflation time in the im(cid:173)
`proved group was 32 ± 19 s versus 29 ± 27 s in the group
`with recurrent symptoms (p = 0.56).
`Seventy patients (74%) had a single balloon procedure;
`the double balloon technique was used in 25 (26%). After the
`use of two balloons, the postvalvuloplasty area was 0.85 ±
`0.09 cm2 and the mean gradient was 38.5 ± 4.7 mm Hg. With
`use of a single balloon, the postprocedure aortic valve
`area was 0.88 ± 0.06 cm2 and the mean gradient was 29.6 ±
`2.7 mm Hg. However, this study was not designed to
`determine if the final aortic valve area is improved by the use
`of two balloons rather than one. Most patients underwent
`double balloon valvuloplasty when a single balloon proce(cid:173)
`dure was deemed inadequate.
`
`Discussion
`Aortic valvuloplasty results in initial improvement in the
`measured outflow gradient in most patients. However, the
`final aortic valve area that results is frequently less than that
`observed after aortic valve replacement (24). A return of the
`aortic valve area toward baseline is probably a certainty at
`some time after the procedure.
`
`Mechanisms of Restenosis
`Why restenosis occurs has not been completely eluci(cid:173)
`dated. Our study suggests that there is no measurable
`technique-related variable that predicts a rapid return of the
`aortic gradient by 6 months. It is more likely that restenosis
`is an inherent property of the architecture of the stenotic
`aortic valve itself. It may also be a function of the status of
`
`Figure 2. Effect of maximal balloon sizes. Maximal balloon diame(cid:173)
`ter was determined by using maximal balloon size derived from the
`maximal diameter of a single inflated balloon or the simple summation
`of the maximal diameter of two balloons. The relation between this
`diameter and the acute change (t;) in the aortic valve area (top panel),
`the acute post valvuloplasty aortic valve area (middle panel) and the
`aortic valve area at recatheterization (RECATH) (bottom panel) is
`shown. The number of patients at each maximal balloon diameter size
`is shown at the bottom of the figure. No clear pattern is evident,
`although most patients had either a 20 or 30 mm maximal diameter
`used. Data are expressed as mean ± 95% confidence interval.
`
`95 PERCENT CONFIDENCE INTERVALS
`FOR FACTOR MEANS
`0.83
`
`-0. 17L-:,75 "",78 -;;2';;-0 -=2';;-2 -=2';;-3 -=2=-7 -:!30;;--;!3-::-2 -::33;:--;:'35;--.!:38;-'
`MAX. BALLOON DIAMETER(s)
`
`0~L-L-L-L-L-~~~~~~
`,5
`'8 20 22 23 27 30 32 33 35 38
`MAX. BALLOON DIAMETER(s)
`
`1.3
`
`1 I Itt tIl 1 1 I
`
`1.0
`
`:I:
`~
`o
`~~ 0.7
`~ E
`<~ 0.4
`~ 0.1
`<
`-0.2
`
`15 18 20 22 23 27 30 32 33 36 38
`MAX. BALLOON DIAMETER(s)
`n = 3 2 60 1 5 1 10 3 3 3 4
`
`Downloaded From: http://content.onlinejacc.org/ on 12/07/2015
`
`Edwards Exhibit 1030, pg. 5
`
`

`
`JACC Vol. 17, No.5
`April 1991:1188-95
`
`BASHORE ET AL.
`RECATHETERIZA TION AFTER AORTIC VALVULOPLASTY
`
`1193
`
`> I I I ! f I I I I I I I I I I I
`
`N
`
`1.6
`.....
`e .3 1.2
`
`f-
`~ 0.8
`11.
`0( 0.4
`
`0(
`
`n - 1 11 12 8 1413 7 7 3
`1 2
`O~-L~~~~-L~~~~~
`5
`7
`9
`11 13 15 17
`3
`NO. OF INFLATIONS
`
`.....
`
`lNe 1.4 ! ~U,~,~ I ,~,I, : I ! f I ! j I f I
`
`::: O. 1 L....J..-'-~-'---'--L-L.-'-.l-.L-'---'--''-'--'---'
`-.
`3
`5
`7
`9
`11 13 15 17
`TOTAL NO. OF INFLATIONS
`
`Figure 3. Effect of number of inflations on aortic valve area. In the
`top panel the total number of inflations is displayed relative to the
`final aortic valve area (A V A) observed after the procedure; in the
`bottom panel the number of inflations is shown relative to the aortic
`valve area at recatheterization (RECATH). The number of patients
`represented is shown within each panel. No obvious relation is
`observed between the aortic valve area and the frequency of balloon
`inflation at the time of the valvuloplasty procedure. Data are
`expressed as mean values ± the 95% confidence interval.
`
`underlying left ventricular systolic performance. Patients
`with a low ejection fraction and a low aortic gradient can
`safely undergo aortic valvuloplasty (25,26), but baseline
`ventricular performance appears to profoundly affect even(cid:173)
`tual outcome (16,17).
`Role of symptomatic status. Fifty-nine percent of this
`patient group had recurrent symptoms at recatheterization
`and 41% were considered clinically improved from their
`baseline state. Despite symptomatic improvement, 69 pa(cid:173)
`tients (72%) had some reduction in the aortic valve area at
`recatheterization, including 62% of those with symptomatic
`
`Figure 4. Relation between average inflation time and the acute
`aortic valve area (AVA) achieved after the procedure. No relation is
`demonstrable between the two variables.
`
`2 .o r - - - - - - - - - - - - - - - - - - - - .
`1.8
`
`1.6
`Ne 1.4
`()
`- 1.2
`• • •
`«
`~'.o :: •••••
`t- 0.8 --
`••
`•
`_ • • •
`(f)
`00.6 ._ .
`CL
`••••
`..
`
`0.4
`
`..
`
`0.2
`
`n=95
`°0~-~370--~6~0-~970-~12~0--~15~0-~18~0~
`INFLATION TIME (sec)
`
`improvement and 80% with recurrent symptoms. The fol(cid:173)
`low-up ejection fraction in the improved subgroup was
`higher than those with recurrent symptoms (59 ± 19% versus
`48 ± 20%) despite a similar value at follow-up for the mean
`aortic gradient (50 ± 20 versus 52 ± 22 mm Hg) and only a
`slightly better aortic valve area (0.7 ± OJ versus 0.6 ±
`
`0.2 cm2). This finding is consistent with the view that
`symptomatic status may be more a function of ventricular
`performance than of the measured aortic valve area or
`gradient (27) .
`These data also reemphasize that valvular stenosis often
`precedes the onset of symptoms in patients with aortic
`stenosis. Patients undergoing aortic valvuloplasty should,
`therefore, be closely monitored for both return of the trans(cid:173)
`valvular gradient and further deterioration of left ventricular
`performance. The lack of recurrent symptoms did not indi(cid:173)
`cate that the aortic valve gradient had not increased. Con(cid:173)
`versely, 20% of patients with recurrent symptoms had little
`evidence for a return of the aortic gradient. Because symp(cid:173)
`toms alone did not consistently correlate with the status of
`the aortic outflow obstruction, the implication is that many
`patients suffer from the combined effects of impaired myo(cid:173)
`cardial function together with variable degrees of outflow
`obstruction. Symptomatic status appears particularly depen(cid:173)
`dent on diastolic ventricular performance characteristics
`after aortic valvuloplasty (27) and this may explain the
`apparent discrepancy observed in this study.
`Role of procedural factors. In addition, this study reveals
`that follow-up status in these patients is probably not pro(cid:173)
`cedure related. Despite the logical concept that aggressive
`efforts should be made to achieve the largest aortic valve
`area possible, the initial aortic valve area after valvuloplasty
`predicted neither symptomatic status nor aortic valve area at
`follow-up. Technical variables such as maximal balloon size,
`mean inflation time and the number of inflations seemed to
`bear no relation to either the initial or the follow-up hemo(cid:173)
`dynamic outcome. These data reemphasize that patient(cid:173)
`related variables are probably more important than proce(cid:173)
`dure-related variables in determining outcome.
`Valve architecture. The intrinsic valve architecture prob(cid:173)
`ably plays a key role in the success of the procedure. For
`example, it has been observed that a poorer outcome and
`more frequent complications may result when valvuloplasty
`is performed on bicuspid aortic valves (12,28,29) and better
`results may be observed when aortic valve stenosis is due to
`commissural fusion, as in rheumatic aortic stenosis (30).
`Most of the patients in this study probably had calcific aortic
`stenosis with a tricuspid leaflet and variable degrees of
`commissural fusion. Better characterization of the inherent
`valve structure in aortic stenosis might allow for better
`selection of patients who would benefit from aortic valvulo(cid:173)
`plasty. This has certainly been the case for percutaneous
`mitral valvotomy (31,32) and may be equally true for aortic
`valvuloplasty. A similar observation has been made regard(cid:173)
`ing the effect of valvuloplasty on congenital aortic valve
`
`Downloaded From: http://content.onlinejacc.org/ on 12/07/2015
`
`Edwards Exhibit 1030, pg. 6
`
`

`
`1194
`
`BASHORE ET AL.
`RECATHETERIZATION AFTER AORTIC VALVULOPLASTY
`
`lACC Vol. 17, No.5
`April 1991: 1188-95
`
`stenosis, where valve morphology is also a major issue in
`determining efficacy of the procedure (33).
`Role of ventricular function. The supporting role that
`underlying ventricular function plays in preventing return of
`the valve gradient and in lessening symptoms is of consid(cid:173)
`erable interest. In this study the symptomatic patients had
`little change in ejection fraction at 6 months, whereas the
`patients with clinical improvement had an increase from a
`mean of 50% to 59%. Ejection phase indexes, such as the
`ejection fraction, are obviously very sensitive to altered
`afterload (34) and hypertrophy alone leads to some degree of
`intrinsic myocardial dysfunction (35). Significant improve(cid:173)
`ment in ejection fraction has been observed in a few patients
`after aortic valvuloplasty (2) and dramatic improvement has
`occasionally been observed in patients after aortic valve
`replacement (36,37). Whether the improvement in left ven(cid:173)
`tricular systolic performance is related to inherent augmen(cid:173)
`tation in contractile function or simply to improved ejection
`dynamics is unclear (38,39).
`Limitations. This study has several limitations. This Reg(cid:173)
`istry was designed simply to tabulate data regarding the
`aortic valvuloplasty procedure in a systematic manner. For
`that reason, though prospectively collected, not all baseline
`and follow-up data were available for all variables, compli(cid:173)
`cating analysis of these data. Whenever possible, we have
`completed the actual number of data points from which the
`results were compiled. This limitation is common to registry
`studies such as this and the data should be interpreted in this
`light.
`An additional major limitation is that this is purely an
`observational study and most patients who underwent re(cid:173)
`catheterization did so for clinical reasons. In fact, this study
`represents only 18% of all potentially eligible patients who
`might have been included. This makes generalizations re(cid:173)
`garding the population as a whole tenuous. Fortunately, less
`symptomatic patients were also included because some
`institutions did attempt to recatheterize patients as part of a
`routine protocol. This does allow for some comparative
`observations.
`Though not the case at the 6 month follow-up, the
`baseline variables in those restudied were similar to those
`patients not recatheterized (Table 1). It is important to
`appreciate that 30% of the patients expired before the 6
`month follow-up anniversary. Obviously, the data are biased
`in favor of patients who were both alive and willing to have
`a repeat catheterization procedure performed. Symptoms at
`follow-up were more common in the recatheterization group
`compared with those who were alive and not undergoing
`recatheterization. We do not know the role that procedural
`and other related facto