Transcatheter Aortic Valve Replacement
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Transcatheter Aortic Valve Replacement Frederick G.P. Welt, MS, MD; Michael J. Davidson, MD; Martin B. Leon, MD; Andrew C. Eisenhauer, MD C ase History: A 77-year-old man presents with fatigue and short- ness of breath with minimal exertion. He is brought into the examination room in a wheelchair due to shortness of breath with ambulation. He has a history of hypertension, diabetes mel- litus, and coronary artery disease with prior stent to left anterior descending artery. Examination is notable for a harsh III/VI late-peaking systolic mur- mur in the right upper sternal border that radiates to the carotid arteries. EKG shows left ventricular hypertro- phy with strain. Laboratory results are notable for serum creatinine of 2.0 mg/dL. Echocardiography is notable for an ejection fraction of 35%, with global hypokinesis in a hypertrophied ventricle. The aortic valve is calcified and stenotic with a peak velocity of 4.2 m/s, a mean gradient of 45 mm Hg, and a calculated aortic valve area of 0.7 cm 2 . Computed tomography scan of the thorax reveals a densely calci- fied aorta (Figure 1). Overview Calcific aortic stenosis is a disease most commonly found in the elderly, with an estimated incidence of 2% to 4% in people 65 years of age, 1 mak- ing it the most common acquired val- vular disease seen in the developed world. Aortic stenosis may affect younger patients who have either con- genitally bicuspid aortic valves or, less commonly in the developed world, a history of rheumatic fever as a child. The pathophysiology of calcific aortic stenosis is not completely understood, but the disease is thought to be second- ary to leaflet stress and shares some features histopathologically with athero- sclerosis; inflammatory-rich plaques de- velop on the leaflets and subsequently become mineralized. 1 The immobility of the aortic leaflets leads to attenua- tion of cardiac output, especially with increased physiological demand, and places the ventricle under a pressure load. This leads to concentric hyper- trophy and diastolic dysfunction and, in late stages, dilatation and systolic failure. The symptoms of aortic stenosis are typically related to a fixed cardiac output with little reserve. This leads to shortness of breath with exertion and, eventually, to frank heart failure. 2 In advanced cases, syncope can also occur. Angina, even in the absence of epicar- dial coronary artery disease, is also com- mon due to the inability to sufficiently perfuse the larger mass of hypertrophied myocardium under high wall tension. Although associated with a long latent period, the prognosis for patients with critical aortic stenosis who develop symptoms is poor, with average survival of 1 to 2 years after the development of congestive heart failure. 3 Early pioneering work of Gorlin and Gorlin 4 established hemodynamic mea- surements in the catheterization labora- tory as a highly reliable method of quan- tifying the severity of aortic stenosis. Doppler echocardiography has largely supplanted invasive studies as the gold standard for diagnosis, showing very reproducible results compared with cath- eterization. 5 The most problematic pop- ulation for accurate diagnosis is patients with low cardiac output. Differentiation of those with pseudo-stenosis from true stenosis often requires the addition of dobutamine to assess contractile reserve and augmentation of gradients. It has been 50 years since the initial implantation of an artificial cardiac From the Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts (F.G.P.W., M.J.D., A.C.E.); and Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York (M.B.L.). The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.111. 032243/-/DC1. Correspondence to Frederick G.P. Welt, MS, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115. E-mail [email protected] (Circulation. 2011;124:2944-2948.) © 2011 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.111.032243 CLINICIAN UPDATE 2944 by guest on October 21, 2016 http://circ.ahajournals.org/ Downloaded from
Transcript of Transcatheter Aortic Valve Replacement
Transcatheter Aortic Valve ReplacementFrederick G.P. Welt, MS, MD; Michael J. Davidson, MD; Martin B. Leon, MD;Andrew C. Eisenhauer, MD
Case History: A 77-year-old manpresents with fatigue and short-
ness of breath with minimal exertion.He is brought into the examinationroom in a wheelchair due to shortnessof breath with ambulation. He has ahistory of hypertension, diabetes mel-litus, and coronary artery disease withprior stent to left anterior descendingartery. Examination is notable for aharsh III/VI late-peaking systolic mur-mur in the right upper sternal borderthat radiates to the carotid arteries.EKG shows left ventricular hypertro-phy with strain. Laboratory results arenotable for serum creatinine of 2.0mg/dL. Echocardiography is notablefor an ejection fraction of 35%, withglobal hypokinesis in a hypertrophiedventricle. The aortic valve is calcifiedand stenotic with a peak velocity of 4.2m/s, a mean gradient of 45 mm Hg,and a calculated aortic valve area of0.7 cm2. Computed tomography scanof the thorax reveals a densely calci-fied aorta (Figure 1).
OverviewCalcific aortic stenosis is a diseasemost commonly found in the elderly,
with an estimated incidence of 2% to4% in people �65 years of age,1 mak-ing it the most common acquired val-vular disease seen in the developedworld. Aortic stenosis may affectyounger patients who have either con-genitally bicuspid aortic valves or, lesscommonly in the developed world, ahistory of rheumatic fever as a child.The pathophysiology of calcific aorticstenosis is not completely understood,but the disease is thought to be second-ary to leaflet stress and shares somefeatures histopathologically with athero-sclerosis; inflammatory-rich plaques de-velop on the leaflets and subsequentlybecome mineralized.1 The immobilityof the aortic leaflets leads to attenua-tion of cardiac output, especially withincreased physiological demand, andplaces the ventricle under a pressureload. This leads to concentric hyper-trophy and diastolic dysfunction and,in late stages, dilatation and systolicfailure.
The symptoms of aortic stenosis aretypically related to a fixed cardiacoutput with little reserve. This leads toshortness of breath with exertion and,eventually, to frank heart failure.2 In
advanced cases, syncope can also occur.Angina, even in the absence of epicar-dial coronary artery disease, is also com-mon due to the inability to sufficientlyperfuse the larger mass of hypertrophiedmyocardium under high wall tension.Although associated with a long latentperiod, the prognosis for patients withcritical aortic stenosis who developsymptoms is poor, with average survivalof 1 to 2 years after the development ofcongestive heart failure.3
Early pioneering work of Gorlin andGorlin4 established hemodynamic mea-surements in the catheterization labora-tory as a highly reliable method of quan-tifying the severity of aortic stenosis.Doppler echocardiography has largelysupplanted invasive studies as the goldstandard for diagnosis, showing veryreproducible results compared with cath-eterization.5 The most problematic pop-ulation for accurate diagnosis is patientswith low cardiac output. Differentiationof those with pseudo-stenosis from truestenosis often requires the addition ofdobutamine to assess contractile reserveand augmentation of gradients.
It has been 50 years since the initialimplantation of an artificial cardiac
From the Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts (F.G.P.W., M.J.D., A.C.E.); and Columbia UniversityMedical Center/New York-Presbyterian Hospital, New York, New York (M.B.L.).
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.111.032243/-/DC1.
Correspondence to Frederick G.P. Welt, MS, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115.E-mail [email protected]
(Circulation. 2011;124:2944-2948.)© 2011 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.111.032243
CLINICIAN UPDATE
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valve in a human.6 Early data showedincontrovertibly that surgical aorticvalve replacement in the patient withcritical aortic stenosis improved symp-toms and dramatically improved sur-vival.7 Balloon aortic valvuloplasty isa technique that, although often lead-ing to early salutary results, has notbeen shown to alter survival comparedwith medical therapy. It is thereforerelegated to use as a bridge to moredefinitive therapy or palliation.
The High-Risk PatientEpidemiological evidence suggests thatthere is a large population with criticalaortic stenosis who are not offered sur-gical valve replacement. Given that thedisease is associated with advanced age,patients often present with comorbidconditions that increase the risk of car-diac surgery. Interestingly, even though
ACC/AHA guidelines specifically statethat age and reduced left ventricularfunction are not contraindications to sur-gical aortic valve replacement,8 these arecommon reasons cited by both surgeonsand referring clinicians for deferring sur-gical therapy.
Transcatheter DevelopmentEarly development of transcathetervalves focused largely on temporary de-vices inserted in either the ascending ordescending aorta to relieve aortic insuf-ficiency for the purpose of allowingpatients to recover from acute hemody-namic instability and become acceptablesurgical candidates. In the early 1990s,Andersen et al conceived of and testedthe first percutaneous transcatheter heartvalve for permanent implantation in aporcine model.9 Subsequent develop-ment resulted in several designs, with the
common themes being bioprostheticvalve material mounted on a stent-likesupport frame and deployed eitherthrough balloon expansion or with theaid of self-expanding superelastic metals(Figure 2).
Clinical TrialsIn 2002, Cribier and others performedthe first transcatheter aortic valve im-plantation (TAVI) in a human.10 Sincethen, numerous registries and small-scale randomized trials have been per-formed that have led to approval in theEuropean Union (CE Mark 2007) andelsewhere for two devices, the balloon-expandable Edwards Sapien valve (Ed-wards Lifesciences Inc., Irvine, CA) andthe self-expanding CoreValve system(Medtronic Inc., Minneapolis, MN). Bysome estimates, �20 000 of these pro-cedures have now been performed inEurope, with registry studies and smallrandomized trials suggesting reasonableoutcomes. Within the United States,both devices have active clinical trialprograms. Whereas the clinical trial in-volving CoreValve has just been initi-ated, the Edwards Sapien valve has beentested extensively via the PARTNER(Placement of AoRTic TraNscathetERValve) trial, and data has already beenreleased.11
Trials for both devices follow a simi-lar design, with 2 patient populationsbeing represented. The first population isthe high-risk surgical group, a group ofpatients identified by a Society of Tho-racic Surgery (STS) score of �10, whichin this patient population predicts a peri-operative mortality of �15%. The STSdatabase was established in 1989 andnow represents �94% of all cardiacsurgical programs in the United States.As of 2004, data were available for �2.4million patients.12 Risk factors consid-ered in the model are numerous, butinclude advanced age, depressed leftventricular function, renal insufficiency,pulmonary disease, cerebrovascular dis-ease, and redo operative status. An on-line website is available for performingindividual calculations of risk.13 The sec-ond group represents the so-called inop-erable or extreme-risk patient, identified
Figure 1. Computed tomography scan of thoracic aorta of patient with critical aorticstenosis. Left panel shows a transverse section and a densely and circumferentially cal-cified aorta (arrow). The right panel shows the calcified segment (arrow) in a 3D recon-structed view.
Figure 2. Left panel shows the Medtronic CoreValve, which consists of porcine tissuesupported on a self-expanding nitinol stent (image courtesy of Medtronic Inc.). The rightpanel shows the Edwards Sapien valve, which consists of bovine tissue supported on aballoon-expandable stainless steel stent (image courtesy of Edwards Lifesciences Inc.).
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by a cardiologist and 2 cardiac surgeonsas having a risk of either death or irre-versible morbidity of at �50%. Thislatter group consists of patients withrisks such as porcelain aorta preventingcross-clamping during surgery, exten-sive mantle irradiation in the past, pul-monary disease prohibiting surgery, andmultiple serious comorbidities.
For both trials, patients must havesymptomatic aortic stenosis with a valvearea calculated by echocardiography of�0.8 cm2 with a mean gradient of�40 mm Hg or a peak velocity acrossthe valve of �4.0 cm/s. For theballoon-expandable Sapien valve, theaortic valve annulus diameter must be18–25 mm. For the self-expandingCoreValve, annular measurementsmust be 20 to 27 mm. In addition, forthe CoreValve, the ascending aortamust be �45 mm in diameter. This isreflective of the fact that, as opposed tothe Sapien valve, which relies on ex-pansion into the calcified mass of thediseased aortic valve, the CoreValvealso depends on anchoring well belowand above the level of the annulus.Severe aortic insufficiency, severe mi-tral valve disease (regurgitation or ste-nosis), and severe tricuspid regurgita-tion are contraindications. In addition,any prior surgical valve repair or re-placement is an exclusion criterion.
Results of the PARTNER trial forinoperable patients have been re-leased.11 These patients were random-ized to transfemoral placement of apercutaneous valve versus best stan-dard therapy, which often includedpalliative balloon valvuloplasty. Thetrial enrolled 358 patients from 21centers. The intraprocedure course isremarkable for almost complete abol-ishment of transaortic gradients. Theprimary outcome of all-cause death at1 year was 30.7% with TAVI com-pared with 50.7% with standard ther-apy (P�0.001). In addition, amongsurvivors, quantitative and qualitativemeasures of symptoms were markedlyimproved. At 30 days post implanta-tion, patients receiving TAVI weremore likely to have suffered stroke(5.0% versus 1.1%, P�0.06) or major
vascular complications (16.2% versus1.1%, P�0.001). These results are re-markable not only for the dramaticreduction in mortality seen with TAVI,but also for the high morbidity associ-ated with this disease in this very sickcohort of patients, with an average agein the mid 80s.
Data from the high surgical riskcohort in the PARTNER trial have alsobeen released.14 Designed as a nonin-feriority trial, 699 patients were ran-domized to either TAVI or standardsurgical therapy. In addition, for thosepatients who had poor femoral access,an option for transapical access via aleft thoracotomy was available, inwhich a sheath was placed into thebeating left ventricle via the apex. At 1year, the primary end point of all-causemortality was 24.2% for TAVI and26.8% in the standard surgical arm(noninferiority P�0.001). The strokeor TIA rate was 8.3% for TAVI and4.3% in the standard surgical arm at 1year (P�0.04).
The PARTNER 2 trial has recentlybeen initiated with a newer device(Edwards Sapien XT valve) that al-lows for a smaller diameter accesssheath. The Medtronic CoreValve trialwill follow a similar design, with ahigh-risk cohort being randomized toTAVI versus standard surgery and anextreme risk group that will receive theTAVI via a registry. No transapicalapproach is planned for the CoreValve,but for those with poor femoral access,axillary or subclavian approaches maybe utilized.
Procedural Details [pleaseclick here for the embedded
movie video of TAVI]The procedure can be thought of in 3distinct stages: (1) obtaining appropri-ate vascular access; (2) placement ofthe valve; and (3) safely removing thelarge-caliber arterial sheath. The pro-cedure is generally performed utilizingboth general anesthesia and transesoph-ageal echocardiography for guidance.Transfemoral cases can take place ineither the catheterization laboratory orhybrid operating room catheterization
laboratory suites. It is important tonote that, given the large accesssheaths required, even cases performedin a percutaneous fashion are at risk ofrequiring open surgical closure. There-fore, a thoroughly sterile environmentand appropriate surgical equipment areimperative. Transapical cases requirean appropriately sterile environmentincluding operating room level venti-lation systems. All procedures are cur-rently performed with both an inter-ventional cardiologist and cardiacsurgeon participating.
Access for the sheath necessary fordelivery of the prosthesis is a criticalportion of the case, given the large sizenecessary. For the PARTNER trial, 2sheaths are provided for the 2 valvesizes: 25-French outer diameter sheathfor the 23-mm valve and 28-Frenchouter diameter for the 26-mm valve.For the CoreValve, the outer diametersheath size is 22 French. Access isobtained from either the right or leftfemoral artery. Some operators per-form surgical cut downs to gain arteri-al access, whereas others use purelypercutaneous techniques with use ofsuture-based closure devices to ensurehemostasis. The arteriotomy is seriallydilated with increasing size dilators,culminating with placement of the de-livery sheath. If the sheath cannot besafely advanced, it is sometimes nec-essary to perform a more extensivedissection and placement of a conduitgraft on a larger caliber segment of theiliac artery to allow placement. In thePARTNER trial, there is the additionaloption of a transapical approach vialeft thoracotomy and apical puncture.
The prosthetic aortic valve is thenadvanced and negotiated around the aor-tic arch across the diseased valve. Care istaken to visualize the aortic valve withboth fluoroscopy and transesophagealechocardiography to allow proper place-ment of the valve. Rapid right ventricu-lar pacing is employed during the actualdilation of the balloon-expandable valveto limit cardiac motion and inadvertentshifting of the valve.
At procedure end, the sheath is re-moved and arterial hemostasis achieved
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either through surgical closure of thearteriotomy or through percutaneous-based closure devices. The latter is asuture-based closure device (Perclose orProstar; Abbott Inc, Abbott Park, IL)placed at the beginning of the procedureand activated at procedure end.
Patients are generally awakened andextubated immediately after the proce-dure. Ambulation is encouraged at day1, and the general hospital course is 3to 5 days. Anticoagulation is achievedwith 6 months of a thienopyridine(Clopidogrel 75 mg/d) and aspirin (75–100 mg/d).
Using data from the PARTNERtrial,11 the most common complicationsof the procedure are �16% incidence ofmajor vascular access complications anda �5% risk of stroke. A small degree ofparavalvar regurgitation is commonlyseen. More significant aortic insuffi-ciency (moderate or severe) is seen in�13% of cases. Valve embolization ei-ther into the ventricle or into the aorta isvery rare. Complete heart block is un-common with the balloon-expandablevalve. However, it may be more com-mon with the self-expanding valve dueto the deeper seating of the valve in theoutflow tract with proximity to the Hisbundle.
Who Should Be Referred?The process of identifying patientswho are potential candidates for thesetrials can be somewhat complicated.Full details of inclusion and exclusioncriteria can be obtained for either trialvia the web.15 Briefly, the process canbe broken down into 3 questions: (1) Isthe patient high risk enough? (2) Doesthe patient meet echocardiographic cri-teria? (3) What is the state of the pa-tient’s vascular anatomy? Figure 3 pro-vides a decision tree analysis.
As discussed above, a simple andquick way to judge surgical risk is touse the online STS risk calculator. AnSTS risk score of �10% is the barrierfor entry into the high-risk cohort ofthe PARTNER trial. For the Core-Valve trial, the wording states that 1cardiologist and 2 cardiac surgeonsmust agree that perioperative mortality
is �15%. The barrier to entry into theinoperable or extreme-risk categoryfor either trial is that the risk of deathor serious irreversible morbidity is�50%.
Iliofemoral access is generally as-sessed by both angiography at the timeof cardiac catheterization (a necessarystudy for all patients considered) andcomputed tomographic angiography.For the PARTNER trial, minimal ves-sel diameter is 7 mm for the 23-mmvalve and 8 mm for the 26-mm valve.The newer PARTNER 2 Sapien XTvalve is deliverable through arteries�6 mm. Similarly, the CoreValve re-quires a minimal diameter of 6 mm. Inaddition, vessels are assessed for ex-cessive tortuosity and calcification,which may impede safe sheath place-ment. Extensive aortic tortuosity orbulky atherosclerotic disease may alsopreclude transfemoral access and indi-cate the need for a transapical or transax-illary approach.
Case Follow-UpOn the basis of overall risk and porce-lain aorta, the patient was deemed
inoperable. Evaluation of his lowerextremity vasculature revealed large-caliber femoral and iliac arteries bilat-erally. He was enrolled in the inoper-able cohort of the PARTNER trial andreceived a 26-mm Edwards Sapienvalve. He is alive 2 years after hisprocedure and has had marked im-provement in his symptoms (nowNYHA class 1–2). He is able to walkmoderate distances with little short-ness of breath and arrives for clinicvisits without the aid of a wheelchair.
DisclosuresDr Welt serves on the Scientific AdvisoryBoard for Medtronic Inc. Drs Davidson andEisenhauer have accepted honoraria fromEdwards Lifesciences Inc. Dr Leon serveson the Scientific Advisory Board for Ed-wards Lifesciences Inc.
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Frederick G.P. Welt, Michael J. Davidson, Martin B. Leon and Andrew C. EisenhauerTranscatheter Aortic Valve Replacement
Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2011 American Heart Association, Inc. All rights reserved.
is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/CIRCULATIONAHA.111.032243
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