Download Percutaneous Therapeutic Interventions for the Mitral Valve

Vanderbilt Heart and Vascular Institute Semiannual Publication |
Spring 2014 | Volume 12 | Issue 14 | VanderbiltHeart.com
Percutaneous Therapeutic Interventions for the Mitral Valve
By Robert N. Piana, M.D., Joseph Fredi, M.D., Michael Petracek, M.D., and Stephen Ball, M.D.
Robert N. Piana, M.D.
Joseph Fredi, M.D.
Michael Petracek, M.D.
Stephen Ball, M.D.
Percutaneous balloon mitral valvuloplasty (PBMV) has long been utilized to treat rheumatic
mitral valve stenosis, but transcatheter options to treat mitral regurgitation have not been
available until now. In 2014 transcatheter interventions are emerging as a viable clinical
option to treat mitral regurgitation in specific scenarios. Practitioners may now be able to
consider these strategies as alternatives to the long-established gold standard of surgical
mitral valve repair or replacement.
Mitral Stenosis
Current guidelines recognize PBMV as the preferred strategy for the treatment of rheumatic
mitral stenosis in specific situations. Anatomic suitability of the mitral valve for balloon
valvuloplasty is typically determined by an echocardiographic scoring system assigning 0
to 4 points for four parameters: mobility, subvalvular thickening, valve thickness and leaflet
calcification. In general, a score ≤8 is considered reasonable for PBMV, provided there
is less than moderate mitral regurgitation and no left atrial thrombus. In patients with
noncalcified pliable valves, mild subvalvular fusion, and no calcium in the commissures, the
procedure can be performed with a high success rate (greater than 90%), low complication
rate (less than 3%), and sustained improvement in 80% to 90% of patients over a 3- to 7-year
follow-up period.1
This complex technique should only be performed by experienced operators. From a
technical standpoint, the intra-atrial septum is punctured to allow access from the right
atrium into the left atrium. A large diameter balloon is then passed across the transseptal
puncture into the left atrium, positioned across the mitral valve into the left ventricle, and
the valve is then dilated to release the fusion of the mitral valve commissures responsible for
the stenosis. Current indications for PBMV in symptomatic patients include:
1.Moderate to severe mitral stenosis (valve area ≤1.5 cm2, mean gradient ≥5 mmHg,
with pulmonary artery systolic pressure ≥30 mmHg) in patients with New York
Heart Association Class II-IV symptoms with appropriate valve morphology (Class I
recommendation);
2.Moderate to severe mitral stenosis with non-pliable, calcified valves in patients at high/
prohibitive risk for surgery (Class II);
3.Valve area >1.5 cm2, but pulmonary artery systolic pressure ≥60 mmHg, pulmonary
wedge pressure ≥20 mmHg, or transmitral gradient ≥15 mmHg with exercise (Class II)
Mitral Regurgitation
Mitral regurgitation (MR) can be classified (Table 1, Figure 1) as organic (regurgitation due
to intrinsic structural abnormalities of the valve) or functional (structurally normal valve
but with MR due to malcoaptation of the valve leaflets). In patients referred for surgery, the
etiology of mitral regurgitation is more commonly organic than functional:
(Continued on page 3)
IN THIS ISSUE
5 Hospital to Home: Optimizing Cardiovascular Care After Hospital Discharge
7 Left Atrial Appendage (LAA) Management: The Non-Pharmacologic Prevention of Stroke in Atrial Fibrillation
10 Incorporating New Guidelines on Cholesterol Management into Clinical Practice
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SPRING 2014
Editorial
By Robert N. Piana, M.D., Editor, Quinn Wells, M.D., Associate Editor, and
Thomas Wang, M.D., Physician-in-Chief
Vanderbilt Heart and Vascular Institute (VHVI) continues to grow. Since the last edition
of Vanderbilt Heart, VHVI has increased the size and capabilities of its physical facilities,
broadened the range of clinical options offered to patients, and accelerated the recruitment
of leading physicians and researchers.
Robert N. Piana, M.D.
Quinn Wells, M.D.
Thomas Wang, M.D.
On Feb. 3, the VHVI Electrophysiology Lab, Cardiac Catheterization Lab and Cardiac
Observation Unit moved to the fifth floor of the Vanderbilt University Hospital Critical
Care Tower. The new space includes state-of-the-art angiography and electrophysiology
labs, as well as two Hybrid OR suites that are fully equipped to serve as both cardiac
catheterization labs and operating rooms. The procedure area utilizes the latest
technologies for hemodynamic monitoring and cardiovascular imaging and intervention.
The move also includes improvements to the overall experience of patients and their
families. Individual holding and recovery rooms provide improved privacy, and a new
waiting area is located nearby, affording greater comfort and convenience for family
members.
A new era in the Department of Cardiac Surgery began in December 2013, with the naming
of Dr. Michael Petracek as the permanent chair. He has led the department as interim chair
since January 2013. Dr. Petracek has been a national figure in cardiac surgery for more
than 30 years, and has helped champion the development of minimally invasive surgical
techniques for cardiac valve surgery. He has also been deeply involved in collaborative
approaches to catheter-based mitral valve replacement and repair. Dr. Petracek’s
appointment invigorates the Department of Cardiac Surgery and signals a continued
commitment to the collaborative environment between cardiac surgery and cardiovascular
medicine that has fueled the success of VHVI.
A key component of VHVI’s growth is the recruitment of nationally and internationally
recognized clinicians and physician scientists. VHVI has added nine faculty members since
last summer, with six more to join in the coming months. These individuals will contribute
to the further expansion of our cardiac transplantation program, the cardio-oncology
program, the arrhythmia center and our translational research efforts. We will profile our
new faculty members in the next issue of Vanderbilt Heart.
VHVI continues to be a leading force regionally and nationally in the provision of cutting
edge options for patients. In this edition of Vanderbilt Heart, a multidisciplinary team of
cardiologists and cardiac surgeons describe catheter-based approaches for the management
of mitral valve disease. Dr. Patrick Whalen and colleagues review the critical role of the left
atrial appendage (LAA) in the pathogenesis of atrial fibrillation-related stroke and emerging
minimally invasive techniques for LAA closure. Equally important to patient outcomes is
the care they receive after hospital discharge. VHVI efforts to optimize this “hospital to
home” transition are described by Dr. Muñoz and colleagues.
We are excited about the continued growth at VHVI. Continue to follow our progress
through Vanderbilt Heart.
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Percutaneous Therapeutic Interventions for the Mitral Valve
Continued from page 1
60-70% of surgical referrals are for “degenerative” MR
(e.g., myxomatous degeneration or mitral valve prolapse),
and 20% for “ischemic” MR and MR due to non-ischemic
dilated cardiomyopathy or hypertrophic cardiomyopathy
(malcoaptation of the leaflets due to mitral annular dilation
or tethering of the mitral leaflets because of ventricular
remodeling with papillary muscle displacement).
Figure 1:
Normal Valve
Degenerative MR-
Degenerative MRProlapse
Fail
Table 1:
Classification of Mitral Regurgitation
Organic (Primary Pathology of the Valve Apparatus)
• Degenerative (e.g., Myxomatous Degeneration)
• Rheumatic
• Endocarditis
• Congenital (e.g., Mitral Cleft)
• Ruptured Chordae Tendineae/Papillary Muscle
Functional (Malcoaptation of the Leaflets Secondary
to Myocardial Process)
• Ischemic
oLeft ventricular remodeling
oPapillary muscle displacement with tethering of
chordae tendineae
oMitral annular dilatation
• Dilated Cardiomyopathy
• Hypertrophic Cardiomyopathy
The timing of surgical repair or replacement for patients with mitral regurgitation is complex. Premature valve surgery
exposes the patient to operative risks and the potential need for long-term anticoagulation. Deferring surgery too long
could lead to heart failure and a dilated cardiomyopathy. When possible, repair of the mitral valve is preferred over
replacement (Class I). However, surgical repair is highly technically demanding, and patients should be referred to
experienced centers with excellent surgical outcomes for this procedure. At 10 years, there is a 7%-10% reoperation rate
after mitral valve repair (similar to the rate after mitral replacement), and 70% of this is due to the original procedure while
only 30% is due to progression of disease.1 The reoperation rate is lower after surgical repair of the posterior leaflet alone as
compared to other leaflet abnormalities. If surgical replacement is performed, the chordal apparatus should be preserved
in order to maximize preservation of left ventricular function. The advantage of mitral valve replacement with preservation
of the chordal apparatus is that MV competence is nearly always assured, LV function is preserved, and postoperative
survival is improved compared with MV replacement with chordal resection. The disadvantage of replacement is the use
of a prosthetic valve, with the risks of deterioration inherent in tissue valves or the need for anticoagulation inherent in
mechanical valves.
Now, for the first time, percutaneous treatment of mitral regurgitation is emerging. The MitraClip Percutaneous Mitral
Valve Repair System (MCS, Abbott Vascular) was designed to approximate a surgical technique (Alfieri) in which the
anterior and posterior leaflets are stitched together at one spot, thereby creating a double orifice mitral valve with less MR
(Figure 2). As mitral annular dilatation often contributes to functional MR, the surgical Alfieri technique also generally
incorporates a mitral annuloplasty in which a ring is placed to shrink the dilated mitral annulus. In the emerging
(Continued on page 4)
Figure 2:
Left panel shows MitraClip prior to deployment. Right panel shows
schematic of resultant double orifice mitral valve after MitraClip
deployment. (Used with permission from Abbott Vascular)
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Percutaneous Therapeutic Interventions for the Mitral Valve
Continued from page 3
transcatheter approach, a transseptal puncture is performed allowing access from the femoral vein to the left atrium. From
this position, using transesophageal guidance, MCS is delivered through the catheter to pin the anterior and posterior
mitral valve leaflets together in one spot. This technique does not incorporate mitral annuloplasty. In October 2013, the
FDA approved the MCS for the treatment of degenerative MR in patients who are poor candidates for surgery, based on the
Endovascular Valve Edge-to-Edge Repair Study (EVEREST) studies.
EVEREST I was a single arm feasibility registry of 55 patients establishing safety of the MCS procedure.2 EVEREST II
randomized 279 patients with moderately severe or severe (grade 3+ or 4+) mitral regurgitation in a 2:1 ratio to undergo
either percutaneous repair or conventional surgery. The study was designed to show non-inferiority of MCS in terms
of efficacy, and superiority in safety. Safety was superior with MCS (48% vs 15%), but this was driven entirely by more
bleeding with surgery.3 There were no differences in death, stroke, myocardial infarction or infection. The efficacy of MCS
proved inferior to surgery. The primary efficacy endpoint of freedom from death, from surgery or mitral-valve dysfunction,
and from grade 3+ or 4+ mitral regurgitation at 12 months was achieved in 55% of the MCS group compared to 73% with
surgery (p=0.007). Mitral valve surgery was required by one year in 20% after MCS versus 2% in the surgical arm (p<0.001).
Thus, MCS was found to be inferior to surgical repair or replacement of the mitral valve in this population. Interestingly, at
four-year followup very few additional surgeries were required in either group (cumulative rate at four years of 24.8% versus
5.5%, p<0.001) and there was no difference in the prevalence of moderate-severe and severe MR or mortality.4 This suggests
that the results with MCS at one year are durable.
Based on these findings, application of MCS has now been focused on patients considered too high risk for surgery.
EVEREST II enrolled 78 patients in a High Risk Registry (EVEREST II HRR) and the Real World Expanded Multicenter
Study of the MitraClip System High Risk (REALISM HR) included 273 patients. These were pooled and retrospectively
analyzed to support FDA approval of the device. At one-year followup in this high-risk population, there was a statistically
significant decrease in the left ventricular diastolic and systolic volumes, a 48% reduction in hospitalization rate, and a
decrease in New York Heart Association class III/IV from 82% to 17%.5 As a result, the FDA advisory panel recommended
approval of the premarket approval application (PMA) for MCS in March 2013, and in October 2013 the FDA followed suit.
The MCS is indicated for the percutaneous reduction of significant symptomatic MR (≥ 3+) due to primary abnormality
of the mitral apparatus (degenerative MR) in patients who have been determined to be at prohibitive risk for mitral valve
surgery by a heart team (a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral
valve disease) and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral
regurgitation.
Vanderbilt Heart and Vascular Institute plans to participate in the Clinical Outcomes Assessment of the MitraClip
Percutaneous Therapy for Extremely High Surgical Risk Patients (COAPT) Trial. Key inclusion criteria include:
• Symptomatic functional mitral regurgitation (≥3+) of either ischemic or non-ischemic etiology;
• Not a suitable candidate for open mitral valve surgery in the judgment of the cardiothoracic surgeon investigator:
• NYHA functional class II, III, or ambulatory IV;
• At least one hospitalization for heart failure in the 12 months prior to enrollment and/or BNP ≥400 pg/mL or NT proBNP ≥1600 pg/mL measured within 90 days prior to enrollment;
• Primary regurgitant jet from the A2 and P2 scallops (and if secondary jet exists, it is clinically insignificant)
As commercialization of this device begins, experienced heart teams will need to apply this technology judiciously in
patients to optimize outcomes.
1.Bonow RO, Carabello BA, Chatterjee K et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart
disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines
for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and
Interventions, and Society of Thoracic Surgeons. Journal of the American College of Cardiology 2008;52:e1-142.
2.Feldman T, Kar S, Rinaldi M et al. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-toEdge REpair Study) cohort. Journal of the American College of Cardiology 2009;54:686-94.
3.Feldman T, Foster E, Glower DD et al. Percutaneous repair or surgery for mitral regurgitation. The New England journal of medicine 2011;364:1395-406.
4.Mauri L, Foster E, Glower DD et al. 4-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. Journal of the American
College of Cardiology 2013;62:317-28.
5.Minha S, Torguson R, Waksman R. Overview of the 2013 Food and Drug Administration Circulatory System Devices Panel meeting on the MitraClip Delivery System.
Circulation 2013;128:864-8.
$
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SPRING 2014
Hospital to Home: Optimizing Cardiovascular Care After
Hospital Discharge
By Daniel Muñoz, M.D., M.P.A., Robin Steaban, M.S.N., R.N., Keith Churchwell, M.D.,
F.A.C.C., Mark Glazer, M.D., F.A.C.C., and Brittany Cunningham, M.S.N., R.N.
Daniel Muñoz, M.D.,
M.P.A.
These are exciting times in cardiovascular patient care. We practice in an era of rapidly
advancing cardiovascular therapeutics, but this progress comes with an increasingly
important challenge: to ensure that patients continue to receive the right care upon
discharge from the hospital, focusing on preventing avoidable and costly hospital
readmissions.1 Across the United States, the readmission of Medicare patients alone is
estimated to cost approximately $26 billion per year, of which $17 billion is spent on
return trips to the hospital that might very well have been avoidable.2 The federal government has made reducing readmissions a central pillar of its approach to
controlling costs while ensuring quality care, an approach codified in the Patient Protection
and Affordable Care Act of 2010.3 In response, hospital systems around the country,
including Vanderbilt, have embarked on an examination of how to systematically create
effective care transitions out of the hospital.
Robin Steaban, M.S.N.,
R.N.
Keith Churchwell, M.D.,
F.A.C.C.
Several studies offer key insights into the scope and complexity of the readmission
challenge. First, the data make clear that the readmission challenge is not disease-specific.
Patients admitted with heart failure, acute myocardial infarction, or pneumonia are more
often readmitted for a different diagnosis, a phenomenon that speaks to their generalized
vulnerability to illness.4 Second, the data also show that reducing readmissions requires a
multidisciplinary approach anchored in both the inpatient and outpatient realms, rather
than a narrow approach that exclusively focuses on a single element of care.5 Third, the
evidence supports the idea that timely outpatient follow-up, ideally within two weeks of
hospital discharge, may help patients avoid readmission.6
From these lessons have emerged several patient-centered quality initiatives at the
Vanderbilt Heart & Vascular Institute. Vanderbilt Acute MyocardiaI Infarction Task Force
In spring 2012, the Vanderbilt Acute Myocardial Infarction (MI) Task Force was formed
to tackle the problem of hospital readmissions after MI. Under the capable leadership of
Brittany Cunningham, MSN, RN, this committee formulated a patient-centered plan to
lower readmission rates. A review of the literature at the time suggested that there was no
(Continued on page 6)
Figure 1:
AMI 30 Day All Cause Unplanned Readmission Rates: Medicare 65+
(Readmission back to Vanderbilt only)
14.0%
•
•
•
•
•
•
•
•
•
•
••
•
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Dec-13
•
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Nov-13
••
Oct-13
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Sep-13
•
Aug-13
10.0%
Jul-13
12.0%
Jun-13
Mark Glazer, M.D.,
F.A.C.C.
8.0%
6.0%
• Rolling 12 month readmission rate
• VUMC Pillar Goal: All Payors
4.0%
2.0%
May-13
Apr-13
Mar-13
Feb-13
Jan-13
Dec-12
Nov-12
Oct-12
Sep-12
Aug-12
Jul-12
0.0%
Brittany Cunningham,
M.S.N., R.N.
%
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Hospital to Home: Optimizing Cardiovascular Care After Hospital Discharge
Continued from page 5
Following hospital
discharge, each
post-MI patient
receives a phone call
from an office nurse
within 72 hours to
review and confirm
medications, answer
any questions, and to
ensure proper, timely
outpatient follow-up.
The program aims to
have every post-MI
patient seen in the
office by a provider
within 10 days of
discharge. Using this
approach, there has
been a significant
observed decline in
MI readmission rates
at Vanderbilt.
(Figure 1)
single identifiable intervention to achieve the goal. Consequently, the Vanderbilt approach
has been deliberately multi-faceted, with a major emphasis on discharge planning and
closer follow-up after discharge. Daily transition "huddles" of nurses, social workers and
physicians occur to identify those patients with MI and to begin assessing personalized,
patient-specific discharge needs. These needs often include home health nursing care and
cardiac rehabilitation. Extra time is devoted at discharge to two key areas: 1) discussing
the proper administration of home medications, and 2) proactively addressing any patient
questions or concerns related to medication list, a list that has often undergone modification
during a hospital stay.
Following hospital discharge, each post-MI patient receives a phone call from an office
nurse within 72 hours to review and confirm medications, answer any questions, and to
ensure proper, timely outpatient follow-up. The program aims to have every post-MI
patient seen in the office by a provider within 10 days of discharge. Using this approach,
there has been a significant observed decline in MI readmission rates at Vanderbilt. Efforts
continue to further reduce MI readmissions at Vanderbilt and to apply lessons learned to
help guide institutional approaches to a host of other cardiovascular conditions.
American College of Cardiology Patient Navigator Program
Vanderbilt is one of 11 hospitals nationwide chosen to participate in the innovative,
recently unveiled Patient Navigator Program (PNP). Sponsored by the American College
of Cardiology with founding support from AstraZeneca, the PNP was developed to
help hospitals address high readmission rates by increasing the focus on the needs of
vulnerable heart disease patients not only while they are in the hospital but following
discharge (American College of Cardiology: Patient Navigator Program, 2013). The hope
is that Vanderbilt, with the help of PNP, can develop and enhance a culture of patientcentered care that can be used in other hospitals around the country. Hospitals selected to
participate in the PNP will be provided improvement strategies and toolkits developed from
other ACC programs such as the Hospital to Home (H2H) Initiative and the Get With the
Guidelines Registry. These ACC programs include more than 1,500 participant hospitals
in the United States.
Conclusion
Institutional and national focus on safe, effective transitions out of the hospital while
preventing readmissions not only makes sound financial sense, but most importantly, is in
the best interest of our patients. To learn more about the ongoing initiatives at Vanderbilt,
please visit us at: VanderbiltHealth.com/heart.
1.Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. The New
England journal of medicine 2009; 360:1418-28.
2.The Revolving Door Syndrome: A Report on U.S. Hospital Readmissions, : The Robert Wood Johnson Foundation;
February 2013.
3.Kocher RP, Adashi EY. Hospital readmissions and the Affordable Care Act: paying for coordinated quality care. JAMA : the
journal of the American Medical Association 2011; 306:1794-5.
4.Dharmarajan K, Hsieh AF, Lin Z, et al. Diagnoses and timing of 30-day readmissions after hospitalization for heart failure, acute
myocardial infarction, or pneumonia. JAMA : the journal of the American Medical Association 2013; 309:355-63.
5.Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. Journal of cardiac
failure 2010; 16:e1-194.
6.Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among
Medicare beneficiaries hospitalized for heart failure. JAMA : the journal of the American Medical Association 2010; 303:1716-22.
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SPRING 2014
Left Atrial Appendage (LAA) Management:
The Non-Pharmacologic Prevention of Stroke in Atrial Fibrillation
S. Patrick Whalen, M.D., Marshall Crenshaw, M.D., Christopher Ellis, M.D., and
Robert N. Piana, M.D.
S. Patrick Whalen, M.D.
Marshall Crenshaw, M.D.
Christopher Ellis, M.D.
Robert N. Piana, M.D.
Atrial fibrillation (AF) is the most common sustained arrhythmia. It has an estimated
prevalence of 1% in the adult population and affects more than 2.5 million in the
United States. AF is responsible for 17% of all strokes (or 135,000 annually).1,2 Whether
paroxysmal or persistent, the two guiding principles in AF
treatment are symptom control and stroke prevention. A
majority of strokes in non-valvular AF originate in the left
atrial appendage (LAA). The LAA is a long, tubular structure
with a narrow neck and large surface area prone to stasis and
thrombus formation (See Figure 1).
Up to 90% of thrombi visualized by transesophageal echo
in AF patients are in the LAA.3.4 Stroke risk in AF is driven
largely by patient comorbidities and may involve LAA
morphology, abnormal endothelial function and platelet
Figure 1: Cast of left
activation.5,6 Standard practice involves oral anticoagulation
atrial appendage
(OAC) for the prevention of systemic thromboembolism in a
majority of AF patients. This has traditionally involved
warfarin but has expanded to include novel oral anticoagulants.
The CHADS2 and CHA2DS2-VASc scoring systems use patient comorbidities to predict
embolic risk and the HAS-BLED scoring system may aid in risk assessment for adverse
effects of systemic anticoagulation.7,8 A large percentage of patients who are candidates for
OAC are not prescribed, do not take, or discontinue therapy due to real or perceived risk of
bleeding or falls, difficulty with monitoring, non-compliance, patient preference, physician
awareness, dietary or drug interactions, or gender disparities.9-11 Given the morbidity of
AF-associated stroke and the challenges of OAC therapy, an effective non-pharmacologic
option is appealing.
Surgical Approaches to LAA Closure
The surgical approach to LAA management involves amputation or occlusion and has
traditionally been performed at the time of cardiac surgery. While several studies have
shown safety and feasibility of LAA closure,12,13 the effectiveness of surgical closure has been
questioned and is often incomplete at follow-up.14 Additionally, no large-scale randomized
trials have tested the efficacy of surgical closure of the LAA for stroke prevention. A new
device (Atriclip, AtriCure Inc, Westchester, Ohio) specifically designed for LAA closure is
now being used. The clip is composed of two parallel, straight, rigid titanium tubes covered
with a knit-braided polyester. It is designed to be implanted from outside the heart through
a thoracoscopic approach and can be done as a stand-alone procedure or in combination
with minimally invasive MAZE surgery for AF.15 (See Figure 2)
(Continued on page 8)
Figure 2: Left: Atriclip; Right: thoracoscopic approach
&
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Left Atrial Appendage (LAA) Management: The Non-Pharmacologic Prevention
of Stroke in Atrial Fibrillation Continued from page 7
Non-Surgical Approaches to LAA Closure
Non-surgical LAA closure may be accomplished using one of several devices implanted percutaneously. Depending on
which device is used, this is done with a purely endocardial or a combined endocardial/epicardial approach.
Endocardial: Early studies providing proof of concept and feasibility of percutaneous LAA occlusion utilized the PLAATO
System (eV3, Plymouth, Minn.) and the Amplatzer Septal Occluder (AGA Medical Corp., Golden Valley, Minn.), initially
designed for closure of atrial septal defects (ASDs) and patent foramen ovale (PFO). The Amplatzer Cardiac Plug (St. Jude
Medical, Minneapolis, Minn.) has evolved out of the septal occluder technology, and is dedicated for LAA closure. The
WATCHMAN (Boston Scientific, Maple Grove, Minn.) device is also used for this purpose.
Epicardial: The LARIAT (SentreHEART Inc. Redwood City, Calif.) device is used for epicardial LAA ligation via subxiphoid access. During the procedure, a 40-mm pre-tied radiopaque suture loop is used to ligate the LAA. The LARIAT
device has been approved for tissue approximation and is currently available at Vanderbilt Heart. LAA closure appears to
be feasible with appropriate anatomy and 96% implant success has been reported with 98% complete occlusion at one year
including those with initial leaks.16,17 (See Figure 3)
In December 2013, the FDA's Circulatory System
Devices Panel voted 13-1 to recommend marketing
approval for the WATCHMAN device. Watchman
consists of a self-expanding nitonol frame which
is delivered via transseptal access to the left atrium
and secured into the LAA via fixation barbs. The
device surface facing the atrial wall is covered by a
porous polyethylene terephthalate membrane. Final
FDA approval is pending.
Figure 3: Procedural
fluoroscopic images of
LARIAT LAA closure
and appearance of
closure from left atrial
side two months after
implant.
The WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients with
AF (PROTECT-AF) study provides us with randomized data comparing LAA occlusion
to warfarin in 542 patients. Subjects in the device arm were on warfarin briefly, and
then treated with dual anti-platelet therapy for six months after implant. The device was
successfully implanted in 88% of cases and 92% of patients discontinued warfarin within
six months. At 1065 patient-years of follow-up the study showed device closure to be noninferior to warfarin. There was a significant decline in procedure-related complications
(largely pericardial effusion) with operator experience from 7.7% to 3.7%.18 Preliminary results from the WATCHMAN
LAA Closure Device in Patients with AF Versus Long Term Warfarin Therapy (PREVAIL) showed implant success of 95%
and adverse safety events only occurring in 2.2% of patients.19
Four-year follow-up data from the PROTECT AF trial have demonstrated a 40% relative risk reduction (stroke,
cardiovascular/unexplained death, systemic embolization) relative to warfarin.20 There are limited data to suggest that
the WATCHMAN device may be implanted safely in patients with absolute contraindications to OAC by placing them on
Plavix for six months and aspirin for life.21 These studies represent compelling data that LAA occlusion may change the
natural history of stroke in patients with non-valvular AF. The results are encouraging, but enthusiasm should be
tempered as it does not include comparison to novel oral anticoagulant therapy, which has changed this landscape over
the last few years.
AF is a common condition and AF-related stroke has catastrophic consequences. The LAA is critical to the pathogenesis
of stroke and as such has been called “our most lethal human attachment.”22 Medical therapy is effective but there are
significant barriers, both real and perceived to OAC in AF patients. LAA occlusion using surgical and catheter techniques
may reduce long-term stroke risk without the adverse effects of chronic anticoagulation and is a rapidly evolving area of
research and clinical practice at Vanderbilt Heart and Vascular Institute.
*
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SPRING 2014
All Cause Mortality
Hazard Ratio with Watchman, 0.66 (95% CI, 0.45 – 0.98)
Patients with Events - %
0.30
0.20
• Watchman
• Control
P = 0.0379
0.10
0.00
No. at Risk
Watchman
Control
0
6
12
18
24
30
36
Time in Months
42
48
54
60
463
244
404
233
389
222
381
216
373
204
341
163
330
150
294
125
202
92
360
193
352
177
Figure 3: The WATCHMAN Device (left) and All-cause mortality data from PROTECT AF trial at four years (right)
(used with permission, Boston Scientific)
1. Go, A. S., et al. (2001). "Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and
Risk Factors in Atrial Fibrillation (ATRIA) Study." Jama 285(18): 2370-2375.
2. Roger, V. L., et al. (2011). "Heart disease and stroke statistics--2011 update: a report from the American Heart Association." Circulation 123(4): e18-e209.
3. Thambidorai, S. K., et al. (2005). "Utility of transesophageal echocardiography in identification of thrombogenic milieu in patients with atrial fibrillation (an ACUTE
ancillary study). ." J Am Coll Cardiol 96: 945-941
4. Beinart, R., et al. (2011). "Left atrial appendage dimensions predict the risk of stroke/TIA in patients with atrial fibrillation." J Cardiovasc Electrophysiol 22(1): 10-15.
5. Al-Saady, N. M., et al. (1999). "Left atrial appendage: structure, function, and role in thromboembolism." Heart 82(5): 547-554.
6. Di Biase, L., et al. (2012). "Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study." J
Am Coll Cardiol 60(6): 531-538.
7. Pisters, R., et al. (2010). "A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey." Chest
138(5): 1093-1100.
8. Fuster, V., et al. (2011). "2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial
fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the
European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society." J Am Coll Cardiol 57(11): e101-198.
9. Camm, A. J., et al. (2012). "2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of
atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association." Eur Heart J 33(21): 2719-2747.
10. Hart, R. G., et al. (2007). "Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation." Ann Intern Med 146(12): 857-867.
11. Contractor, T. and A. Khasnis (2011). "Left Atrial Appendage Closure in Atrial Fibrillation: A World without Anticoagulation?" Cardiol Res Pract 2011: 752808.
12. Crystal, E., et al. (2003). "Left Atrial Appendage Occlusion Study (LAAOS): a randomized clinical trial of left atrial appendage occlusion during routine coronary artery
bypass graft surgery for long-term stroke prevention." Am Heart J 145(1): 174-178.
13. Garcia-Fernandez, M. A., et al. (2003). "Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis: a transesophageal
echocardiographic study." J Am Coll Cardiol 42(7): 1253-1258.
14. Katz, E. S., et al. (2000). "Surgical left atrial appendage ligation is frequently incomplete: a transesophageal echocardiograhic study." J Am Coll Cardiol 36(2): 468-471.
15. Ailawadi, G., et al. (2011). "Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial." J Thorac Cardiovasc Surg 142(5): 1002-1009, 1009.
e1001.
16. Bartus, K., et al. (2013). "Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience." J Am Coll
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17. Massumi, A., et al. (2013). "Initial experience with a novel percutaneous left atrial appendage exclusion device in patients with atrial fibrillation, increased stroke risk, and
contraindications to anticoagulation." Am J Cardiol 111(6): 869-873.
18. Holmes, D. R., et al. (2009). "Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised
non-inferiority trial." Lancet 374(9689): 534-542.
19. Holmes, D. (2013). "Randomized Trial of LAA Closure vs Warfarin for Stroke/Thromboembolic Prevention in Patients with Non-valvular Atrial Fibrillation (PREVAIL)."
Interventional Innovation Summit Lecture. CIT. CNCC, Beijing, China. 20 March 2013.
20. Reddy V, D. S., Sievert H, et al (2013). "Long term results of PROTECT-AF: the mortality effects of left atrial appendage closure versus warfarin for stroke prophylaxis in AF.
." Heart Rhythm Society LBCT Scientific Sessions, May 9, 2013, Denver, Colorado.
21. Reddy, V. Y., et al. (2013). "Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix
Feasibility Study With Watchman Left Atrial Appendage Closure Technology)." J Am Coll Cardiol 61(25): 2551-2556.
22. Johnson, W. D., et al. (2000). "The left atrial appendage: our most lethal human attachment! Surgical implications." Eur J Cardiothorac Surg 17(6): 718-722.
(
VA N D E R B I L T H E A R T
|
SPRING 2014
Incorporating New Guidelines on Cholesterol Management into
Clinical Practice
By Raphael See, M.D., and Sergio Fazio, M.D., Ph.D.
Raphael See, M.D.
Sergio Fazio, M.D., Ph.D.
While the 2013
updated guidelines
bear a number
of similarities to
NCEP-ATP III,
there are several key
differences which
should be taken
into account when
deciding how to best
manage a patient’s
cholesterol and CV
risk in the clinical
setting.
In November 2013 new American College of Cardiology/American Heart Association
(ACC/AHA) guidelines were published regarding cholesterol management for the
prevention of cardiovascular (CV) events1, 2 as a proposed update to the previous National
Cholesterol Education Program and Adult Treatment Program III guidelines (NCEP-ATP
III) published in 2002.3 While the 2013 updated guidelines bear a number of similarities to
NCEP-ATP III, there are several key differences which should be taken into account when
deciding how to best manage a patient’s cholesterol and CV risk in the clinical setting.
Key differences in the 2013 guidelines
The guiding and fundamental principle of NCEP-ATP III is individually tailored
low-density lipoprotein cholesterol (LDL-C) treatment goals in proportion to an
individual’s predicted CV risk. In brief, NCEP-ATP III suggests that all subjects with
prior atherosclerotic CV disease or with diabetes be placed in the high-risk category, and
recommends using the Framingham Risk Score to assess the 10-year risk for CV events in
all other patients. Escalating levels of predicted risk (i.e. low, moderate, or high) warrant
increasingly aggressive LDL-C treatment goals (i.e. <160 mg/dL, <100-130 mg/dL, or <70100 mg/dL).
Like NCEP-ATP III, the 2013 ACC/AHA guidelines also begin with an estimation of 10year CV risk; however, this risk estimate is now made using a new tool called the Pooled
Cohort Equation (PCE).4, 5 The Framingham Risk Score has been previously criticized
due to the Framingham original cohort being a relatively homogeneous population.
The PCE attempts to reflect a more diverse, contemporary United States population by
incorporating additional data from several large racially and geographically diverse cohort
studies and also adds ethnicity and diabetes as additional clinical factors. As the PCE is
mathematically complex, a spreadsheet-based online calculator (http://my.americanheart.
org/cvriskcalculator) is available and several unofficial applications for smartphones and
tablets exist as well.
Following CV risk assessment with the PCE, lipid-lowering therapy is then chosen
according to the level of 10-year risk. In contrast to NCEP-ATP III, the 2013 guidelines
no longer recommend specific LDL-C target levels but instead propose fixed-dose statin
treatment with potency in proportion to the predicted 10-year CV risk (Table 1). Using this
strategy, it is recommended that the highest risk individuals – either clinical atherosclerotic
CV disease or LDL-C levels >190 mg/dL – receive high-potency statin treatment.
Otherwise, individuals with predicted 10-year risk for CV events >7.5% by the PCE qualify
for moderate-potency statin treatment. Moderate-potency statin therapy is recommended
for diabetics in general, but higher risk individuals with diabetes (10-year risk >7.5%)
should receive a high-potency statin. Lower-potency statin treatment is only recommended
when otherwise indicated higher potency treatments are not tolerated. In addition, nonstatin treatments are not recommended as first-line agents due to lack of evidence clearly
associating decreased adverse CV outcomes with their use.
This new dosing strategy reflects the greatest departure from NCEP-ATP III as the emphasis
was previously on achieving specific LDL-C targets, with the specific choice of drug being
less important. The authors of the 2013 guidelines cite two main reasons for this new
approach. First, by simplifying the recommended statin treatment regimens (and removing
the need for dose titration), the authors hope to make lipid management more accessible to
BL
VA N D E R B I L T H E A R T
|
SPRING 2014
Table 1:
Clinical characteristics warranting either high- or low-potency statin treatment. When not specified otherwise, these
recommendations cover individuals 40-75 years of age.
High-potency statin indicated
(>50% LDL-C expected reduction)
atorvastastin 40-80 mg, rosuvastatin 20-40 mg
• Clinical atherosclerotic coronary artery disease
(any age)
• Fasting LDL-C >190 mg/dL (age >20 years)
• Diabetes AND 10-year risk >7.5%
Moderate-potency statin indicated
(35-50% LDL-C expected reduction)
atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin
20-40 mg, pravastatin 40-80 mg, lovastatin 40 mg,
fluvastatin 40 mg BID
• Diabetes AND 10-year risk <7.5%
• 10-year risk >7.5%
• Age >75 years
all health care providers. Second, the pivotal randomized clinical trials (RCT) demonstrating benefit with statin treatment
did not target specific LDL-C levels but instead used fixed statin dosing in their primary design. In a sense, using fixed-dose
statin treatment may therefore represent evidence-based practice more reflective of RCT data. The only statement about
LDL-C lowering in these guidelines is the expected range of 35% -50% reduction for the moderate potency regimen and
>50% reduction for the high potency regimen, which can be used to determine patient adherence.
Special exceptions
Of note, the 2013 guidelines are purposefully silent regarding statin use in patients receiving hemodialysis or with systolic
congestive heart failure despite clinically apparent high CV risk. In these populations, RCTs of statin use have not clearly
demonstrated a preventative benefit.6, 7 Similarly, high-potency statin use has not consistently demonstrated a preventative
benefit above and beyond moderate-potency regimens in individuals >75 years of age, and an individualized approach is
recommended, taking potential risk for drug interactions, toxicity, and patient preferences into account.
Points to consider
Though intended to simplify and facilitate appropriate statin treatment, controversy remains concerning the 2013 update.
The PCE has been criticized due to lack of prospective validation and an apparent tendency to overestimate CV event
risk.8 Others have taken issue with the decision to exclusively use RCT-derived evidence in the formulation of these
recommendations despite the existence of other high-quality, non-RCT data.
As with any set of consensus guidelines, it is always important to consider the individual being treated, taking care not to
let guidelines replace or supersede clinical judgment. For example, according to the 2013 guidelines, statin therapy would
not be recommended for a normotensive 65-year-old woman with total cholesterol of 220 mg/dL, HDL-C of 40 mg/dL,
and LDL-C of 180 mg/dL as her 10-year CV risk is 5.9% by the PCE. Similarly, a 52-year-old man with multiple coronary
stents who is tolerating high potency statin treatment with an LDL-C of 120 mg/dL (from a baseline of 205 mg/dL) would
not receive additional therapy to drive the LDL lower according to these new guidelines. Reflecting the controversial nature
of the new guidelines, it is important to note that they have not been endorsed by the American Diabetes Association,
the Endocrine Society, or the National Lipid Association, who all continue to support a strategy based on targeting riskappropriate LDL-C goals.
Conclusion
The updated 2013 cholesterol treatment guidelines attempt to address a changing United States demographic and simplify
decision-making in primary and secondary prevention. While the impact of these changes remains to be seen, the
importance of personalizing the care of each patient has not changed.
(Continued on page 12)
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Incorporating New Guidelines on Cholesterol Management into Clinical Practice
Continued from page 11
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Sorlie P, Levy D, Stone NJ, Wilson PW. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart
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AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Suleymanlar G, Tsakiris D, Tesar V, Todorov V, Wiecek A, Wuthrich RP, Gottlow M, Johnsson E, Zannad F.
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