Circulation. 2007;115:e334-e338
doi: 10.1161/CIRCULATIONAHA.106.657098
(Circulation. 2007;115:e334-e338.)
© 2007 American Heart Association, Inc.
Percutaneous Balloon Aortic Valvuloplasty Revisited
Time for a Renaissance?
Hidehiko Hara, MD;
Wesley R. Pedersen, MD;
Elena Ladich, MD;
Michael Mooney, MD;
Renu Virmani, MD;
Masato Nakamura, MD;
Ted Feldman, MD;
Robert S. Schwartz, MD
From the Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minn (H.H., W.R.P., M.M., R.S.S.); CV Path, International Registry of Pathology, Gaithersburg, Md (E.L., R.V.); Division of Cardiovascular Medicine, Toho University, Ohashi Medical Center, Tokyo, Japan (M.N.); and Evanston Northwestern Hospital, Evanston, Ill (T.F.).
Correspondence to Robert S. Schwartz, MD, Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, 920 E 28th St, Ste 620, Minneapolis, MN 55407. E-mail rss{at}rsschwartz.com
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Introduction
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Case Presentation: A 92-year-old woman presented with progressive
heart failure in the setting of known aortic valve stenosis.
Despite aggressive medical therapy, she remained in New York
Heart Association functional class IV. She lived in an assisted-care
facility and wanted to engage in more vigorous daily activities.
She did not wish to undergo surgical aortic valve replacement.
An echocardiogram showed a left ventricular ejection fraction
of 50%. The aortic valve was heavily calcified and severely
stenotic, with a mean gradient of 64 mm Hg and an aortic valve
area of 0.46 cm
2.
The patient was offered balloon aortic valvuloplasty, to which she and her family consented. A retrograde approach with a 23-mm balloon was used. A total of 3 inflations were carried out across the aortic valve during simultaneous rapid ventricular pacing at 220 bpm. The postvalvuloplasty mean gradient was reduced to 28 mm Hg, and the aortic valve area increased to 0.98 cm2. She was seen in the clinic 6 months later with stable functional class II symptoms and remained quite satisfied with her improved lifestyle.
Calcific aortic stenosis (AS) is the most frequent expression of valvular heart disease in the Western world, with increasing prevalence expected as the population ages. Three percent of all adults 
75 years of age have moderate or severe AS, and it is the leading indication for valve replacement in Europe and the United States. Surgical aortic valve replacement is the preferred treatment strategy for patients of all age groups, although it has limitations in the octogenarian and nonagenarian populations. Open heart approaches are limited by higher perioperative risk, prolonged recovery, and poor quality of life after surgery.1 The surgical 30-day mortality rate for the nonagenarian population is 
17% in 1 contemporary series, with 40% mortality by 13 months.2
Less invasive percutaneous options are needed for poor-surgical-risk patients with severe AS. Balloon aortic valvuloplasty (BAV) is currently the only approved catheter-based option for nonsurgical patients, a procedure that has been underused in those patients relegated to medical therapy alone. This procedure fell from favor secondary to perceived procedural complexity, suboptimal initial results, and high restenosis rates in the 6 to 12 months after the procedure.3 As the number of very elderly with this disease increases, especially those in whom surgical options are not available, an effective and less invasive treatment of severe AS is essential. About one third of patients with severe AS are not referred for valve replacement surgery because of the risks perceived by both patients and physicians. The use of BAV for palliation of symptoms has been undervalued in this difficult-to-treat patient group.
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Pathophysiology of AS
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A normal aortic valve leaflet consists of 3 layers (
Figure 1).
AS is considered a form of atherosclerosis, and early valve
lesions show subendothelial cellular and extracellular lipid
accumulation on the aortic side of leaflets, much like what
occurs in atherosclerotic disease. Such lesions include oxidized
low-density lipoprotein, lipoprotein(a), inflammatory cells,
and calcification. Severely stenotic leaflets have prominent
calcification with lipocalcific changes on the aortic side of
leaflet.
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Figure 1. Layered architecture of normal aortic valve leaflet. The ventricular surface has a black-staining elastic layer (ventricularis). A dense collagenous layer (fibrosa) extends toward the aortic surface. The spongiosa is a loose connective tissue layer rich in proteoglycan.
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Active bone formation is an important component of AS.4 Early lesion initiation results from endothelial layer disruption caused by mechanical forces such as shear stress and abnormal blood flow patterns. Lipid accumulation, especially with low-density lipoprotein, begins within the leaflet subendothelial layer and is modified by inflammatory and cytokine interactions. The angiotensin-converting enzyme cascade also works locally within the aortic leaflet, causing fibroblasts within the fibrosa layer to differentiate into myofibroblasts wherein the angiotensin I receptor is highly expressed. The myofibroblast cell plays a central role in the process because it is believed to differentiate into an osteoblast-like cell phenotype, which in turn promotes deposition of calcified nodules and bone formation.
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Novel Relevant Pathophysiological Insights From In Vivo 3-Dimensional Imaging
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Investigations into the relationship between aortic valve calcium
and stenotic area by multislice computed tomography show causal
mechanisms.
5 Three-dimensional images reveal important information
about leaflet calcification and stenosis severity.
Figure 2 supports the observation that extravalvular calcification affects
leaflet motility, especially when calcium accumulates in the
outflow tract and aortic root. Calcification within these locations
may severely restrict leaflet motion and enhance stenosis severity.
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Figure 2. Three-dimensional volume-rendering images reveal that extravalvular calcification of the valve leaflet, especially toward the left ventricle outflow tract, may restrict the motion of the leaflet, which can be worked as a hinge point.
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Current Therapy and Results
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Surgical Replacement
Surgical valve replacement should be considered the treatment
of choice for severe AS patients regardless of age. Moderate-to-severe
AS occurs in 5% of individuals 75 to 86 years of age, and critical
AS is seen in >5% of those >85 years of age.
6 Increasing
numbers of octogenarians and nonagenarians are presenting with
severe AS for consideration of open heart surgery, and physicians
are increasingly confronted by the growing dilemma of finding
suitable therapy for elderly patients who are often poorly suited
for traditional valve replacement surgery. Surgical success
rates for these very elderly patients are improving but remain
suboptimal. In-hospital death and stroke rates may be as high
as 8.5% and 8%, respectively.
1 Mean duration of postoperative
hospital stay in most reports is >2 weeks for very elderly
patients, with most being discharged to nursing care facilitates.
Furthermore, many elderly patients refuse surgery despite favorable
outcomes, making less invasive, percutaneous therapy an attractive
option for enhancing their quality of life. Moreover, disability
often results from aortic valve replacement surgery in elderly
patients. Less specific cognitive deficits also are common.
More than half of all octogenarians are discharged to rehabilitation
facilities, even after minimally invasive approaches are used,
and >20% are rehospitalized within 1 month.
7
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Aortic Valvuloplasty as a Forgotten Therapy
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Percutaneous aortic valvuloplasty was developed as a nonsurgical
option in the 1980s. It was found to have a role in managing
unstable and critically ill patients such as those in cardiogenic
shock or refractory heart failure. A mean age of 78±9
years was reported in the National Heart, Lung and Blood Institute
(NHLBI) valvuloplasty registry and was typical of "younger"
patients who underwent BAV 2 decades ago. A consistent limitation
for this therapy among younger patients with greater longevity
was the high restenosis rate and the need for reintervention.
BAV was thus found to be of limited utility for many of these
patients who were acceptable candidates for aortic valve replacement.
High complication rates and in-hospital mortality also were reported early in the experience, suggesting complications in 25% of patients (167 of 672) within 24 hours of the procedure and documenting death in 3% (17 of 672).8 The most common complication was transfusion in 20%, related predominantly to vascular entry site complications (136 of 672; Table 1).8 Cumulative cardiovascular mortality before discharge was 8% in the NHLBI registry. Restenosis and recurrent hospitalization were common, although survivors reported fewer symptoms over the subsequent 1.5 years.3 Most patients who are very elderly often are considered too frail to undergo BAV or aortic valve replacement. In a comparable patient population without AS, median expected survival was only 2 years, regardless of valve condition.9 The most important predictor of event-free survival after BAV was left ventricular function at baseline (ejection fraction >25%).10 BAV may be a forgotten therapy, but analysis suggests that it offers benefits to the very elderly high-risk patient who is looking for significant symptomatic improvement that is not available from medical therapy alone. Table 2 shows informal guidelines currently used by our institutions to select patients suitable for BAV.
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Mechanisms of Dilation
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The effects of BAV on the aortic valve are poorly understood,
but several mechanisms are likely. The most common effect is
intraleaflet fractures within calcified nodular deposits. These
represent leaflet hinge points and may increase flexibility
within the calcified aortic root to improve valve opening. Other
possible mechanisms include scattered leaflet microfractures,
cleavage planes along collagenized stroma, and uncommon separation
of fused leaflets. Enhanced compliance of the rigidly calcified
adjacent aortic root, which may follow BAV, may further contribute
to greater leaflet flexibility. That no single mechanism has
been proved suggests insufficient data and leaves unanswered
the question of novel strategies for valvular dilation.
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Silver Linings to a Dark Cloud
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Several technical and procedural improvements are now available
for BAV that did not exist 20 years ago when Cribier first described
the procedure.
10a Rapid ventricular pacing (200 to 220 bpm)
now arrests mechanical systole to preserve balloon stability
across the aortic valve during inflation. The Inoue balloon
(typically used for mitral valvuloplasty) improves immediate
post-BAV aortic valve area compared with conventional and retrograde
BAV.
11 Enhanced valve opening may be achieved through leaflet
hyperextension into the broader aortic root diameter. The "dumbbell"-shaped
Inoue balloon locks on the aortic valve and can accomplish leaflet
hyperextension with a rounded distal end without overstretching
the valve annulus engaged by the narrower neck.
12 Furthermore,
inflation–deflation times are faster, and given the required
antegrade transvenous approach, peripheral arterial complications
are less likely. Immediate post-BAV valve area is affected by
pre-BAV severity and correlated with improved hemodynamic long-term
follow-up.
Investigations suggest that repeat balloon valvuloplasty in AS patients across multiple age groups (59 to 104 years) may improve 3-year survival rates over a single dilatation.13 Repeat BAV can be performed without additional complications. Most patients have symptomatic relief for a year or more. The value of symptomatic palliation in this population cannot be understated. Minimizing the need for repeated hospitalizations for heart failure has a large impact on quality of life for these 80- to 95-year-old patients. Misconceptions often include a higher-than-reported rate of complications such as perioperative stroke, post-BAV aortic insufficiency, and myocardial perforation. In a series of 86 patients 80 years of age, no myocardial perforations occurred, and only 1 patient developed severe aortic regurgitation.14 Only 1 of 86 patients suffered stroke, and the overall periprocedural mortality was 2.2%. Data from our group show successful simultaneous coronary stenting with BAV in 11 patients (mean age, 87 years; range, 79 to 99 years) between July 2003 and May 2006 without complications or in-hospital mortality (unpublished data, Minneapolis Heart Institute BAV registry). These data represent a favorable trend that is important given the incidence of severe coronary artery disease in these patients of 50%.
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Valvular Restenosis and Prevention
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External Beam Radiation
The Radiation Following Percutaneous Balloon Aortic Valvuloplasty
to Prevent Restenosis (RADAR) pilot trial suggests that external
beam radiation may significantly reduce restenosis. Restenosis
in the RADAR pilot study was 20% at 12 months in a population
with an average age of 89 years, suggesting utility in elderly
patients.
15 This surprising benefit may occur through the previously
demonstrated ability of external beam radiation therapy to limit
the formation of scar tissue and heterotopic ossification previously
reported in restenotic aortic valves.
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Potential for Transcatheter Implantation and Antirestenotic Drug Therapy
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Percutaneous heart valve implantation with stent-based valves
has been performed in initial feasibility studies in inoperable
patients with severe AS. Immediate and early clinical improvement
has been achieved in small patient numbers with this technique.
BAV will play a crucial role in preparing the stenotic aortic
valve for the prosthetic implantation. Further device improvements
and long-term follow-up are required in these novel implantation
devices before premarket approval is obtained.
Antirestenotic drug therapy after BAV has not been attempted, but preclinical studies to prevent calcification have been investigated in surgical settings. Because drug-eluting stents have replaced brachytherapy in the management of coronary artery disease and restenosis, local drug elution into dilated aortic valves may be possible, in theory, to prevent restenosis after BAV or work primarily to stimulate bone regression.
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Conclusions and Summary
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Aortic valvuloplasty strategies should be reevaluated, given
the enhanced knowledge of vascular and valvular biology that
permits targeted therapy to prevent restenosis and to delay
or reverse valve mineralization. The increasing numbers of poor
surgical candidates in the expanding very elderly population
mandate less invasive methods such as BAV to improve quality
of life. The time has arrived for balloon aortic valvuloplasty
to be revisited, and a resurgence of this procedure is becoming
possible through improved knowledge and refined transcatheter
device developments.
The patient presented in this Clinician Update needs to be followed up regularly to monitor for evidence of restenosis. If restenosis of the aortic valve occurs and is clinically significant, a repeat BAV can be performed.
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Acknowledgments
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Disclosures
None.
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References
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- Kolh P, Kerzmann A, Lahaye L, Gerard P, Limet R. Cardiac surgery in octogenarians: peri-operative outcome and long-term results. Eur Heart J. 2001; 22: 1235–1243.[Abstract/Free Full Text]
- Edwards MB, Taylor KM. Outcomes in nonagenarians after heart valve replacement operation. Ann Thorac Surg. 2003; 75: 830–834.[Abstract/Free Full Text]
- Otto CM, Mickel MC, Kennedy JW, Alderman EL, Bashore TM, Block PC, Brinker JA, Diver D, Ferguson J, Holmes DR Jr. Three-year outcome after balloon aortic valvuloplasty: insights into prognosis of valvular aortic stenosis. Circulation. 1994; 89: 642–650.[Abstract/Free Full Text]
- Feldman T, Glagov S, Carroll JD. Restenosis following successful balloon valvuloplasty: bone formation in aortic valve leaflets. Cathet Cardiovasc Diagn. 1993; 29: 1–7.[Medline]
[Order article via Infotrieve]
- Koos R, Mahnken AH, Sinha AM, Wildberger JE, Hoffmann R, Kuhl HP. Aortic valve calcification as a marker for aortic stenosis severity: assessment on 16-MDCT. AJR Am J Roentgenol. 2004; 183: 1813–1818.[Abstract/Free Full Text]
- Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. 1993; 21: 1220–1225.[Abstract]
- Goodney PP, Stukel TA, Lucas FL, Finlayson EV, Birkmeyer JD. Hospital volume, length of stay, and readmission rates in high-risk surgery. Ann Surg. 2003; 238: 161–167.[CrossRef][Medline]
[Order article via Infotrieve]
- Percutaneous balloon aortic valvuloplasty: acute and 30-day follow-up results in 674 patients from the NHLBI Balloon Valvuloplasty Registry. Circulation. 1991; 84: 2383–2397.[Abstract/Free Full Text]
- Horstkotte D, Loogen F. The natural history of aortic valve stenosis. Eur Heart J. 1988; 9 (suppl E): 57–64.
- Kuntz RE, Tosteson AN, Berman AD, Goldman L, Gordon PC, Leonard BM, McKay RG, Diver DJ, Safian RD. Predictors of event-free survival after balloon aortic valvuloplasty. N Engl J Med. 1991; 325: 17–23.[Abstract]
- Cribier A, Savin T, Saoudi N, Rocha P, Berland J, Letac B. Percutaneous transluminal valvuloplasty of acquired aortic stenosis in elderly patients: an alternative to valve replacement? Lancet. 1986; 1: 63–67.[CrossRef][Medline]
[Order article via Infotrieve]
- Eisenhauer AC, Hadjipetrou P, Piemonte TC. Balloon aortic valvuloplasty revisited: the role of the Inoue balloon and transseptal antegrade approach. Catheter Cardiovasc Interv. 2000; 50: 484–491.[CrossRef][Medline]
[Order article via Infotrieve]
- Feldman T. Transseptal antegrade access for aortic valvuloplasty. Catheter Cardiovasc Interv. 2000; 50: 492–494.[CrossRef][Medline]
[Order article via Infotrieve]
- Agarwal A, Kini AS, Attanti S, Lee PC, Ashtiani R, Steinheimer AM, Moreno PR, Sharma SK. Results of repeat balloon valvuloplasty for treatment of aortic stenosis in patients aged 59 to 104 years. Am J Cardiol. 2005; 95: 43–47.[CrossRef][Medline]
[Order article via Infotrieve]
- Eltchaninoff H, Cribier A, Tron C, Anselme F, Koning R, Soyer R, Letac B. Balloon aortic valvuloplasty in elderly patients at high risk for surgery, or inoperable: immediate and mid-term results. Eur Heart J. 1995; 16: 1079–1084.[Abstract/Free Full Text]
- Pedersen WR, Van Tassel RA, Pierce TA, Pence DM, Monyak DJ, Kim TH, Harris KM, Knickelbine T, Lesser JR, Madison JD, Mooney MR, Goldenberg IF, Longe TF, Poulose AK, Graham KJ, Nelson RR, Pritzker MR, Pagan-Carlo LA, Boisjolie CR, Zenovich AG, Schwartz RS. Radiation following percutaneous balloon aortic valvuloplasty to prevent restenosis (RADAR pilot trial). Catheter Cardiovasc Interv. 2006; 68: 183–192.[CrossRef][Medline]
[Order article via Infotrieve]
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Introduction
Pathophysiology of AS