Trans-Catheter Therapy for Valvular Heart · PDF fileTrans-Catheter Therapy for Valvular Heart Disease Sanjay K. Gandhi Section on Cardiology

Trans-Catheter Therapy for

Valvular Heart Disease Sanjay K. Gandhi

Section on Cardiology

Disclosures

• Investigator – Medtronic

Objectives

• Review clinical challenges in treating high risk patients with aortic stenosis

• Discuss the development of trans-catheter aortic valve replacement(TAVR) and potential indications for its use.

• Review the surgical treatment options for mitral regurgitation

• Discuss the development of trans-catheter treatment for mitral regurgitation

Adult Valvular Heart Disease:

The Scope of the Problem

New York state

Supino PG, et al. Adv Cardiol. 2002;391-6.



• Mitral Stenosis

• Mitral Regurgitation

• Aortic Stenosis

• Aortic Regurgitation



• Mitral Stenosis

• Mitral Regurgitation

• Aortic Stenosis

• Aortic Regurgitation

Valvular Heart Disease:

Aortic Stenosis

• Most common cardiac valvular lesion in US

• With progressive narrowing of the valve orifice, adaptive and maladaptive concentric left ventricular hypertophy develops in response to the pressure overload on the ventricle.

• Eventually leads to decreased coronary flow, diastolic dysfunction, and systolic dysfunction

• Symptomatic development of syncope, angina, and heart failure conveys an extremely poor prognosis

• Surgical valve replacement has historically been the only effective therapy

Wake Forest School of Medicine

• Mortality difference for people with

symptomatic AS treated with Aortic

Valve Replacement (AVR) versus

those not undergoing this procedure

is one of the most striking in

medicine

• AVR can be withheld in such

patients only when compelling

contraindications exist

Symptomatic AS

Treatment: Surgical AVR

1Schwartz et al. Circulation 1982; 66: 1105-10.

AVR

No AVR

Standard of care for

Severe AS

Bioprosthetic Valves

Mechanical Valves

Valvular Heart Disease: Aortic Stenosis Surgical valve replacement has been associated with

higher surgical morbidity and mortality in certain high risk

patient subsets

• Elderly patients with comorbidities

• Severely reduced left ventricular systolic function

• Severe COPD

Surgical mortality in general is 2-8%; it may be in excess of

20% in certain high risk populations. (Eltchaninoff H, et al, J

Interven Cardiol 2003;16:515-521. Florath I, et al, Ann Thorac Surg

2003;76:75-83. Connoly H, et al, Circulation 2000;1940-1946)

Almost one-third of patients with severe valvular lesions

who may benefit from interventions are declined for

operative treatment because of high risk status (Iung B, et al,

Eur Heart J 2003;24:1231-43).

Valvular Heart Disease: Aortic Stenosis

Treatment of Elderly Patients

Sundt M, et al, Circulation. 2000;102[suppl III]:III-70-III-74.


Treatment of Elderly Patients

Florath I, et al. Ann Thorac Surg 2003;76:75-78


Severely Reduced Left Ventricular Function

Powell E, et al. Arch Intern Med. 2000;160:1337-1341


Severe Symptomatic AS: Percent of patients treated

EU US

Untreated

Surgery

Pellikka2 Charlson1 Lung3 Bouma4

59% 68% 70%

40%

41% 32% 30% 60%

Multiple studies quantify the extent of under-treatment

1Charlson E, Legedza AT, Hamel MB. J Heart Valve Dis 2006;15: 312-321.

3Lung B, Baron G, Butchart E, et al. Eur Heart J 2003; 24: 1231-1243.

4Bouma BJ, van den Brink, et al. Heart 1999; 82: 143-48.

2Pellika PA, Sarano ME, et al. Circulation 2005; 111: 3290-95.

Is Surgical AVR Underutilized?

Old age Co-morbidities Frailty Prior cardiac surgery Dementiae


AS Challenges-Case Study

EF 35%

Valvular Heart Disease: Aortic

Stenosis

• Surgical valve replacement significantly improves long

term outcome and decreases mortality in symptomatic

patients with severe aortic stenosis.

• But what options are available for patients who are

deemed “too high risk” for surgery?

• ? Balloon Valvuloplasty?

36 to 80% restenosis in one year

Inpatient mortality up to 13%

High rate of stroke, vascular complications, and

aortic regurgitation

Aortic Stenosis and Treatment

Options for “Inoperable” Patients • Back to the ground rules for Interventional Cardiology:

Opening blockages is good – stents are even better.

• Why not put a prosthetic valve inside a stent and

deliver it with it a catheter?

Eltchaninoff H et al, J Interven Cardiol 2003;16:515-521


Percutaneous Treatment of AS


History of Percutaneous Valve Implants


Percutaneous Treatment of AS

Percutaneous Heart Valves(PHV) for

Aortic Stenosis

Cribier A et al, J Am Coll Cardiol 2004;43:698-703

PHV for Aortic Stenosis:

The Cribier-Edwards Valve • Series of first six patients(implantation attempted April,

2002 – August, 2003)

• 5 men, 1 women; mean age 75(57-91)

• All had been denied surgical valve repair

• All with severe CHF; 3 with cardiogenic shock

• All with aortic valve area < 0.6 cm2

• Only one had significant concurrent coronary disease


The Cribier-Edwards Valve

Age M/F Comorbidities

57 M Severe PAD, lung CA, silicosis, chronic pancreatitis

80 M Severe AR, CVA, ESRD, asbestosis, prostate CA

91 M Cachexia, bedridden>1 month

63 M Rectal Adenocarcinoma, Severe COPD, ESRD

80 F Metastatic breast CA, COPD, Kyphoscoliosis

77 M Stroke, Porcelain aorta, ESRD

Patients 2 and 6 developed hemodynamic collapse during balloon pre-dilation requiring “transient external massage and adrenalin.”

Cribier A, et al. J Am Coll Cardiol 2004;43:698-703

•PHV for Aortic Stenosis:


• 5 of 6 patients survived the procedure.

• In patients who survived the procedure, aortic

valve area increased from 0.49 + 0.08 to 1.66 +

0.13 cm2 (p < 0.04)

• Mean valve gradient decreased from 38 + 11 to

5.6 + 3.4 mmHg

• 3 patients died of non-cardiac causes

• 2 patients stable at 8 week followup

Cribier A, et al. J Am Coll Cardiol 2004;43:698-703



• Followup in first 36 patients attempted implant reported

• Mean age 80 + 7 (62-91)

• 28% patients with EF < 0.30

• 76% with CAD

• 38% with ESRD

• 41% with severe lung disease

• 38% with pulmonary hypertension

• 27% with PAD

• 27% with at least moderate regurgitation

Cribier A, et al. J Am Coll Cardiol 2006;47:1214-23.

The Cribier-Edwards Valve • 36 patients enrolled; Implantation attempted in 33; 27 successful

implantations; 21 patients survived to 30 day followup

• 11 patients alive at nine month followup(9-26 months)

Cribier A, et al. 2006;47:1214-23.


Stent Valve Options for Percutaneous Treatment of AS


Hemodynamic Characteristics of Stent Valves

Wake Forest School of Medicine Coeytaux R R et al. Ann Intern Med

2010;153:314-324

Percutaneous Treatment of AS: Evidence Base

One large RCT of

TAVR vs AVR

PARTNER

(CoreValve

trial pending)


Edwards SAPIEN Medtronic CoreValve

CE Mark Nov 2007 April 2007

Aortic Stent Valve Available OUS-Clinical Trials US


TAVR Worldwide Experience

Over 30,000 implants in 34 countries as of July 2011


Sapien Stent Valve


Percutaneous Treatment of AS: PARTNER Trial

AVR mortality

> 10%

AVR mortality

> 50%

Severe symptomatic AS (AVA <0.8cm2; peak AVG >60, mean AVG > 40


PARTNER Trial: Inoperable Cohort (cohort B)

Leon et al. NEJM 2011; 363:1597-1607.

50% reduction in mortality

at 12 months with TAVR


PARTNER Trial: Inoperable Cohort (cohort B)

Leon et al. NEJM 2011; 363:1597-1607.


PARTNER Trial: High Risk Patients (cohort A)

Smith et al. NEJM 2011; 364:2187-98.

TAVR and AVR outcomes

similar at 12 months


PARTNER Trial: High Risk Patients (cohort A)

Smith et al. NEJM 2011; 364:2187-98.

PARTNER: 2 Year Outcomes:

Surgery vs TAVR

Kodali, S. et al. NEJM, 3/26/21012(epub)

PARTNER: 2 Year Outcomes: Surgery vs TAVR







Inoperable Patients

Makkar, R. et al. NEJM, 3/26/21012(epub)


Inoperable Patients



Inoperable Patients



CoreValve Stent Valve

Wake Forest School of Medicine Piazza et al Eurointervention 2008; 4:242-9

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the

third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded

evaluation registry 1-year following CE mark approval.

Aortic regurgitation

CoreValve post CE Mark Registry

AVGradient


CoreValve US Pivotal Trial

(Inclusion and exclusion criteria same

as PARTNER Trial)


CoreValve TAVR Trial

Inclusion Criteria

Severe symptomatic AS - AVA < 0.8mm2 and peak

AVG >60 mmHg or mean AVG > 40 mmHg

High Risk-est. 30 day mortality >15%, <50%

Extreme Risk-not surgical candidate (est. 30 day

mortality >50%)

Both expected to survive at least one year

Vascular access, annulus, sinus of Valsalva,

and ascending aorta size appropriate



Principal Exclusion Criteria

Untreated sig CAD

BMS within 30 days; DES within 6 months

EF < 20%

eGFR <20cc /min

GIB within 3 months

CVA within 6 months


CoreValve-Case Study Balloon Aortic Valvuloplasty (BAV)


CoreValve-Case Study Final Result

Before TAVI After TAVI



Evaluations

Echo

Cardiology, CTS evaluations

PFTs

Cardiac cath within 1 year

Cardiac CT

CTA chest, abdomen, and pelvis


TAVR Challenges

Durability

Vascular access complications

Stroke risk

Pacemaker (CoreValve)

Aortic regurgitation


Vancouver Experience of TAVR Durability (SAPIEN)


Femoral artery 6-9mm (18-27 Fr)

“Percutaneous” treatment AS

Requires very large catheter sizes


“Percutaneous” treatment AS

Requires very large catheter sizes


Access site needs to be carefully evaluated

(largest source of peri-procedural complications)

Avulsion of external iliac artery

Dissection of left subclavian artery


Alternatives to femoral access

Trans-apical (SAPIEN)

Subclavian Iliac conduit

Direct aortic


Peri-procedural Stroke


TAVI in lower risk patients-it’s coming

TAVR Summary

Serruys, PW. PCR 2010

Breakthrough technology and treatment

Downsizing delivery systems under development

should reduce complications

Durability to be determined

Training standards; who will implant is an issue

Ultimate role in treatment of all pts with severe

AS remains to be determined

Mitral Regurgitation

• Degenerative/Myxomatous

• Rheumatic

• Infectious

• Ischemic/Functional

Mitral Regurgitation:

Surgical Treatment

Surgical Replacement

Surgical Repair


Surgical Treatment


Surgical Repair


Surgical Treatment


Surgical Repair:

Annuloplasty

Resection with Annuloplasty

Shortening of the Papillary Muscle

Chordal Replacement and Shortening

Papillary Muscle Sling

Surgical Relocation of the Posterior Papillary Muscle

Alfieri Edge-to-Edge Repair

Alfieri Edge-to-Edge Repair for

Mitral Regurgitation

Maisano F, et al. European J of Cardiothorac Surg. 1998;13:240-246


Maisano F, et al. European J of Cardiothorac Surg. 1998;13:240-246

Freedom from reoperation

N = 121 113 had concurrent annuloplasty 33 required additional reconstruction 68% Degenerative 15% Endocarditis 12% Rheumatic 5% Ischemic

Survival


With or Without Annuloplasty

Kherani A, et al. Ann Thorac Surg 2004;78:73-76.


The Basis For a Percutaneous Option?

Feldman T, et al. J Am Coll Cardiol 2005;46:2134-40

Procedure

A catheter is introduced through the patient’s skin in the groin area, and is guided from the femoral vein to the mitral valve.

Then, a smaller delivery catheter that holds the MitraClip device is introduced through the first catheter so that the Clip can be guided into place and attached to the leaflets of the mitral valve.

Then, a smaller delivery catheter that holds the MitraClip device is introduced through the first catheter so that the Clip can be guided into place and attached to the leaflets of the mitral valve.

MitraClip attached to the mitral valve leaflets.

Once the Clip is securely attached and MR is reduced, it is deployed and the catheters are removed.

EVEREST II: Trial Design

Feldman, T, et al. N Enl J Med 2011;364:1395-406.

EVEREST II: Baseline Data


EVEREST II: Outcomes






Conclusions

• TAVR is an emerging treatment strategy for

patients with critical aortic stenosis who are

deemed “inoperable.”

• Studies are ongoing to determine if TAVR may be

an acceptable alternative treatment strategy for

critical aortic stenosis patients deemed “high risk”

for surgery.

• Trans-catheter strategies are being developed for

treatment of patients with mitral regurgitation.

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Trans-Catheter Therapy for Valvular Heart · PDF fileTrans-Catheter Therapy for Valvular Heart Disease Sanjay K. Gandhi Section on Cardiology