vascular institute’s vascular conference advances in atrial fibrillation treatment ·...

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Advances in Atrial Fibrillation Treatment: Ablation and Left Atrial Occlusion Strategies

J. Michael Mangrum, MD

Associate Professor of Medicine

Ted Turner Clinical Scholar in Atrial Fibrillation

Director, Atrial Fibrillation Center

University of Virginia

February 17, 2018 Guerrieri Heart & Vascular Institute’s 22nd Annual Coastal Cardiac & Vascular Conference

Disclosures

• Research Grants: Medtronic, Boston Scientific, St. Jude Medical, CardioFocus

• Advisory Board: Medtronic, CardioFocus

• Speaker: Medtronic, CardioFocus, St. Jude Medical

Outline

•AF introduction

•AF ablation

• LAA occlusion

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Atrial Fibrillation: Facts

Single most common sustained cardiac dysrhythmia

In 2010, estimated 2.6 million Americans had AF and expected 12 million in 2050

Men have a 1.5 fold higher risk of developing AF

Risk of AF increases with age. (Note: only 1% of patients with AF are less than 60 years old)

Stroke is 5X more common in patients with AF

About 1 in 7 strokes are caused by AF

Hypertension is the most notable risk factor for developing AF

The estimated cost of treating Americans with AF is $26 billion per year

Deshpande, et al. Card Electrophysiol Clin 2014;6:1‐4

Definitions

• Paroxysmal AF• AF that terminates spontaneously or with intervention within 7 days of onset

• Early Persistent AF• AF sustained beyond 7 days but < 3months in duration

• Persistent AF• AF sustained beyond 7 days

• Long‐standing Persistent AF• Continuous AF of greater than 12 months duration

• Permanent AF• Decision made to remain in AF with no further attempts at rhythm control

Calkins, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2017;14:e275‐e444.

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Indications for Catheter Ablation of Atrial Fibrillation

• Symptomatic AF refractory/intolerant to at least one class I or III antiarrhythmic medication

• Paroxysmal Class I

• Persistent Class IIa

• Long‐standing persistent Class IIb

• Symptomatic AF prior to initiation of class I or III antiarrhythmic medication

• Paroxysmal Class IIa


• Long‐standing persistent Class IIb


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Indications for Surgical Ablation of Atrial Fibrillation:concomitant open (such as mitral valve)



• Persistent Class I

• Long‐standing persistent Class I






Indications for Surgical Ablation of Atrial Fibrillation:concomitant closed (such as CABG or AVR)






• Paroxysmal Class IIa


• Long‐standing persistent Class IIa


Indications for Surgical Ablation of Atrial Fibrillation:stand‐alone or hybrid

• Symptomatic AF refractory/intolerant to at least one class I or III antiarrhythmic medication and failed one or more attempts at catheter ablation or prefer a surgical approach

• Paroxysmal Class IIb




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Cox JL. Current Problems in Cardiology 1983:3‐60

Cox JL. Current Problems in Cardiology 1983:3‐60

• The resulting concept…is based on that of a maze in which there is one entrance point into the box (SAN), one true conduction route between the entrance and exit, and several blind alleys along the route. Thus we refer to this surgical procedure as the maze procedure.

• Between 1987‐91, 22 pts underwent this procedure

Cox, JL, et al. JAMA 1991;266:1976‐1980.

Cox JL, et al. J Thorac Cardiovasc Surg 1995;110:473‐84

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Multiple electrode catheter

2 thermocouples

per electrode

Introducer

sheath

14 coil electrodes

• A Focal Source of Atrial Fibrillation treated by Discrete Radiofrequency Ablation• Jais P, et al. Circulation 1997;95:572‐576

Haissaguerre M, et al. N Engl J Med 1998;339:659‐66

Pulmonary Vein Isolation (PVI)

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Cardiac Ablation for Atrial Fibrillation

• Goals• High clinical efficacy• Low complication rates

• Achieve durable pulmonary vein isolation with least amount of tissue damage/destruction

• How to achieve durable pulmonary vein isolation?• Lesions to be contiguous and transmural

• Why is there re‐connection?• Role of edema or inefficient energy deliver?

• Lack of energy titration based on patients’ anatomy?

Tools for PVI in US

• Radiofrequency (point‐by‐point ablation)

• Cryoballoon

• Laser

HeartLight Technology – Main components

Console

Balloon Catheter Sheath

Endoscope

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Case (UVA 8.15.17)

• Mr. G is a 52 y.o. male with a 3 year h/o PAF. Current AF episodes monthly

• Med Hx: HTN

• Meds: Failed flecainide and metoprolol

• ECHO: Normal LV function; LA size 4.1 cm

• Plan: PVI

Case (UVA 8.15.17)

Case (UVA 8.15.17)RSPV First set of lesions

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Case (UVA 8.15.17)

Case (UVA 8.15.17)

• RIPV not isolated

• Would like more antral RPV lesions

• LPVs limited by esophageal temperature rise

• Re‐deployed balloon in RPVs

• Increased the balloon size

• Ablated more on periphery of endoscopic view

Case (UVA 8.15.17)RSPV Second set of lesions

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Case (UVA 8.15.17)

Case (UVA 8.15.17) [Before ablation]

Case (UVA 8.15.17) [After 1st encirclement]

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Case (UVA 8.15.17) [After second encirclement of RPVs]

LaserFluid Cooled RF

Lesion Quality

Dukkipati SR, d’Avila A, Reddy VY et al. Circ Arrhythm Electrophysiol. 2010,3:266-73

Laser Ablation

PACE. 2015 Jul 14. doi: 10.1111/pace.12696.

LASER Ablation

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Baseline Regional LA/PV thickness

S

I

AP

S

I

PA

S

I

PA

RSPV

RIPV

S

I

AP

S

I

AP LSPV

LIPV

n= 8162 measurements in 30 patients

2.88±0.76

2.43±0.88

2.73±1.20

2.46±1.20

2.56±0.88

2.57±0.98

2.47±1.15

2.66±1.02

2.64±1.08

2.79±1.05 3.68±1.83

5.10±1.40

3.60±0.89

3.28±0.94

2.98±1.17

2.28±0.76

4.06±2.16

2.78±0.87

3.88±1.75

3.06±0.90LC

> 3 mm

< 3 mm

Importance of energy titration

Without energy titration, there will likely be regions without transmural lesions or there will be injury to adjacent structures

LSPV Pre 2 LSPV Post 2

HRS 2015; PO06‐60

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Laser

RIPV pre RIPV post

HRS 2015; PO06‐60

Percent change in wall thickness post ablation

0.0

10.0

20.0

30.0

40.0

50.0

60.0

LSPV(S)

LSPV(P)

LSPV(I)

LSPV(A)

LIPV(S)

LIPV(P)

LIPV(I)

LIPV(A)

RSPV(S)

RSPV(P)

RSPV(I)

RSPV(A)

RIPV(S)

RIPV(P)

RIPV(I)

RIPV(A)

RF

Laser

Region of each PV

Percent (%

) Increase in wall

thickness

% change PV [RF vs. Laser]

RF = 40.2%Laser = 14.4%

RF = 32.5%Laser = 11.8%

RF = 15.3%Laser = 2.7%

RF = 17.0%Laser = 5.3%

RF =29.5%Laser = 8.5%

Ablation Strategies for Persistent AF

PVI only

PVI + non‐PV triggers

PVI + linear lesions (Eg: 2C3L)

PVI + CFAE

PVI + linear lesions + CFAE

Step‐wise approach

PVI + “catheter MAZE” (including RA ablation)

PVI + entire posterior wall

Rotor/driver domain ablation

PVI + rotor/driver domain ablation

Hybrid AF ablation

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Substrate and Trigger Ablation for Reduction in Atrial Fibrillation Trial II [STAR AF II]

589 persistent AF patients randomized in 1:4:4 ratio to PVI only (67pts); PVI + CFAE (263pts); PVI + linear (259pts)

F/U 18 months

Primary endpoint: Freedom from any AF > 30 seconds after 1 procedure

Verma A, et al. N Engl J Med 2015;372:1812‐22

Verma A, et al. N Engl J Med 2015;372:1812‐22

59%

49%46%

P = 0.15


48 centers from 12 countries

Persistent AF patients. (Excluded if paroxysmal, persistent AF > 3 years, or LA > 6.0 cm)

Ablation performed with: Open‐irrigated ablation

EnSite Velocity, St. Jude Medical*

Post‐procedure 3 month ‘blanking’ period and drugs then stopped

If recurrence post 3 months, could start (or re‐start) AA drug and if appropriate re‐ablation [same randomized strategy] at 3‐6 months post initial procedure

Monitoring

Clinical Assessment, 12 lead ECGs , 24 Hr Holters at 3,6,9,12, and 18 months, and transtelephonic monitoring weekly for 18 months and with any symptom

Verma A, et al. N Engl J Med 2015;372:1812‐22*Funded the study


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Why the result?

Additional ablation result in new iatrogenic areas of arrhythmogenesiswhere the tissue is incompletely ablated or linear block not achieved?

Perhaps neither CFAE or lines are the correct supplemental targets?

Automated CFAE maps may not be accurate?

Can we be assured of durable PVI?

Ablation endpoint was not AF termination.

For persistent AF, is total elimination of AF necessary or is AF burden reduction an acceptable endpoint?

Driver Domains in Persistent Atrial Fibrillation (Haissaguerre M, et al. Circulation 2014;130:530‐538)

Aims

Evaluate use of non-invasive 3D Mapping (ECM) to identify drivers in distinct categories of persistent atrial fibrillation (AF).

Methods

• Prospective, non-randomized

• RF Ablation times compared to matched controls

• n=103

• Driver ablation + PVI; + linear lesions if AF not terminated

Results

Acute results: 82/103 patients experienced AF termination (80%).

Outcomes:

58/90 (64%) in stable sinus rhythm at 12 mos

16/90 repeat ablations for atrial tachycardia (12) or AF (4)

85% with AF termination free from AF at 12 mos

Anatomical Distribution of AF Drivers (above) Distribution of Mean Number of

Rotations per Patient (n=103) (below)

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AFACART Trial. (Knecht S, et al. Europace. 2017;19:1302‐1309)

Aims

To evaluate the utility of ECG mapping as a practical tool prior to ablation for persistent AF in centers with no practical experience of the system

Methods

• Multicenter (8 centers), prospective non-randomized

• N=118, PsAF <1 year, refractory to >1 AAD, LA diameter <55mm

• Primary endpoint: Acute AF to SR or AT

Results

• Driver‐only ablation resulted in AF termination in 64% of the patients (75/118)

• Acute termination rates were not significantly different across all 10 centers.

• At 1 year, 77% of patients were free from AF recurrence after only a single procedure (78% off AADs)

• 14/25 recurrences were persistent of which 4 could not be managed by DC cardioversion ± new AADs ± repeat ablation

• 3 month blanking period (Failure =AF or AT > 30secs)

• Holters at 3 , 6*, 9, & 12* months (*=72 hours)

Results Cont. 14/25 recurrences were persistent. Remaining 11 AF

recurrences were paroxysmal 37% of all patients developed atrial tachycardia managed

by AAD ± repeat ablation

Chronic Freedom from AF

46

Noninvasive mapping

47

Obtain CT scan for heart‐torso geometry2

Select beats and create mapsRecord cardiac signals from vest3 4

Prep patient and apply vest1

Phase Mapping (Atrial Fibrillation)

Phase Map Composite Map

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CardioInsight Physician Training | Confidential

AF Recording and map generation

Define phase intervals Phase maps Composite map

Identify intervals with >1000ms (recommend 1200ms) over enough samples (ex. 10+) to be representative of rhythm under investigation.

(Segment CT and combine AF recordings)

Create a playable phase map for each processed map interval

Displays composite of all detected phase map activity

Interval1

X >10

49

X >10

UVA Case 027

TVMV

Termination while ablating posterior left atrium around the left PVs

UVA Case 027

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UVA Case 018

UVA Case 001

TV

UVA Case 017

TV

UVA Case 020

TV MVMV

MV

Initial experience at UVA compared to European experience

• All types of atrial fibrillation (PAF, persistent, long‐standing persistent)

• Both Index cases and Repeat ablation cases

• Did mapping both pre‐procedure and intra‐procedure

• Modified 7 segment model to subsegments (total of 19)

• Endpoint was ablation to sinus rhythm

• Used contact force sensing ablation catheters

University of Virginia Experience• Initial Experience (February, 2017 – November, 2017)

• Atrial – 40 • Afib (Paroxysmal) – 6 (Index cases – 4, Repeat cases – 2)• Afib (Persistent) – 25 (Index cases – 12, Repeat cases – 13)• Afib (Long‐Standing Persistent) – 4 (Index cases – 0, Repeat cases – 4)• Atach – 3 (Index cases – 1, Repeat cases – 2)• Note: 1 patient non‐inducible, 1 patient atrial flutter and not mapped

• Ventricular – 5 • PVC – 5

• CRT – 6 • CardioInsight™ Mapping System was used pre‐procedure and intra‐procedure

• For the above Atrial Arrhythmia patients, the ablation strategy was to ablate to sinus rhythm

• Achieved in 28/38* (74%) CardioInsight™ cases • Presented in Afib/AT [27]. 18/27 (67%) ablated to SR• Presented in SR [13]. Induced. 11/13 (85%) ablated to SR

*Could not induce sustained Arrhythmia in 1 case and unable to map the flutter in 1 case

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0

2

4

6

8

10

12

14

AT Paroxysmal Persistent Long‐StandingPersistent

Acute Procedural Success: Type of Atrial Arrhythmia Cases and Ablation to Sinus Rhythm

Index Repeat

100% 100%

100% 100%

92% 62%

0%

Number of Patien

ts

Did not terminate with ablation

0

2

4

6

8

10

12

14

AT Paroxysmal Persistent Long‐StandingPersistent

Clinical Success – Arrhythmia‐free

Index Repeat

Mean f/u = 5.1 months

100% 100%

75% 50%

83%92%

0%

Note: Same patient in 2 cases with deep RAA trigger (not a mapping issue)

Note: Same patient in 2 cases with ASD repair and arrhythmias due to surgery

Number of Patien

ts

Did not terminate with ablation

Indications for Surgical Ablation of Atrial Fibrillation:stand‐alone or hybrid

• Symptomatic AF refractory/intolerant to at least one class I or III antiarrhythmic medication and failed one or more attempts at catheter ablation or prefer a surgical approach

• Paroxysmal Class IIb




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Hybrid Cardiac Ablation

Driver and Mangrum. J Thorac Dis 2015;7:159‐164


1 = PVI2 = Roof3 = Inferior4 = Anterior5 = LSPV to LAA6 = Inferior to CS7 = SVC8 = Intercaval

a = mitral isthmusb = CTI

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Persistent Patients (45 pts)

60±126045±7204.8±0.9

1.7±0.5

2.1±0.647

Age (years)Male (%)LVEF (%)CHF?LA Diameter

# of Failed Ablations

# of AADBMI >30 (%)

Surgery +Catheter (15)

RepeatCatheter (30)

59±146751±9164.5±0.8

1.8±1.2

1.7±0.833

P

nsnsnsnsns

ns

ns

Mahapatra S, et al. Ann Thorac Surg 2011;91: 1890‐1898


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Port Placement

• Right Side

• Left Side

Bipolar clamp

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GP Mapping and AblationHigh Frequency Stimulation

Positive Vagal Response

Epicardial Exit Block

PericardialInsertion of

Lig of Marshall

LAA

Left Pulmonary

Artery

LSPV

Ligament ofMarshall

Ligament of Marshall

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Atricure Exclude Appendage Device

Multipolar catheter in each PV

Check Box Lesion

• Check Posterior wall

• Entrance block

• Exit block with pacing

• Often Roof Line gap

• LI‐MI line includes CS burn

• Use fluoro to confirm place LI‐MI line same place as surgeon

• Isoproternol run limited by pressure

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Track Atrial Flutters

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LSPV post

LIPV post

RSPV post

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RIPV post

SVC post

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Di Biase, et al. HRS 2010

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CAP STOPS LSP AF – Procedure MetricsPost Procedure Voltage Map – Isolation of Posterior LA & PVs

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Oral Anticoagulation is Standard of Care, but Not Ideal for All NCDR Pinnacle Registry

Warfarin

• Bleeding risk

• Daily regimen

• High non‐adherence rates

• Regular INR monitoring

• Food and drug interaction issues

• Complicates surgical procedures

Novel Oral Anticoagulants

• Bleeding risk

• Daily or 2x/daily regimen

• High non‐adherence rates

• Complicates surgical procedures

• Limited reversal agents

• High cost

1. Hsu, J et al. JAMA Cardiol. Published online March 16, 2016. doi:10.1001/jamacardio.2015.0374

Use of OACs in AF Patients peaks at ~50%,use declines with increasing risk

Despite NOAC Adoption and Ability to Switch NOACs, Adherence to Anticoagulation Remains a Challenge

Source: Martinez C, et al. Therapy Persistence in Newly Diagnosed Non-Valvular Atrial Fibrillation Treated with Warfarin or NOAC. A Cohort Study. Thromb Haemost. 2015 Dec 22;115(1):31-9. doi: 10.1160/TH15-04-0350.

~30% of NOAC patients stop taking any drug at 2 years

Connection Between Non‐Valvular AF‐Related Stroke and the Left Atrial Appendage

1. Stoddard et al. Am Heart J. (2003)2. Goldman et al. J Am Soc Echocardiogr (1999)3 Blackshear JL. Odell JA., Annals of Thoracic Surg (1996)

• Stasis-related LA thrombus is a predictor of TIA1 and ischemic stroke2.

• In non-valvular AF, >90% of stroke-causing clots that come from the left atrium are formed in the LAA3.

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Left Atrial Appendage Closure Devices(FDA Approved Devices as of January, 2018)

Endocardial Epicardial

Watchman™ Lariat™ Atriclip™

WATCHMAN™ LAAC Device

Indications for Use

The WATCHMAN Device is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non‐valvular atrial fibrillation who:

• Are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2‐VASc scores and are recommended for anticoagulation therapy;

• Are deemed by their physicians to be suitable for warfarin; and

• Have an appropriate rationale to seek a non‐pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin

• One-time implant that does not need to be replaced

• Performed in a cardiac cath lab/EP suite, does not need hybrid OR

• Performed by a Heart Team

• IC/EP or IC&EP, TEE, General Anesthesia, Surgical Back- up, WATCHMAN Clinical Specialist

• Transfemoral Access: Catheter advanced to the LAA via the femoral vein

WATCHMAN™ Left Atrial Appendage Closure (LAAC) Device Procedure

• General anesthesia*

• 1 hour procedure*

• 1-2 day hospital stay*

* Typical to patient treatment in U.S. clinical trials

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WATCHMAN™ ‐Most Studied LAAC Device

Key Trials N Highlights

PROTECT AF1

(2005‐2008)707 Prospective, randomized 2:1, non‐inferiority trial of LAA closure vs. warfarin.

CAP2

(2008‐2010)566

Prospective registry allowing continued access to the WATCHMAN Device and gain further information prior to PMA approval.

PREVAIL3

(2010‐2012)407

Prospective, randomized 2:1, non‐inferiority trial to collect additional information on the WATCHMAN Device.

CAP2(2012‐2014)

579Prospective registry allowing continued access to the WATCHMAN Device prior to PMA approval.

EWOLUTION(2013‐2015)4*

1025Prospective registry allowing all patients receiving a WATCHMAN Device at participating centers in Europe, Middle East and Russia

Total patients >3,000 ~9,000 Patient‐Years of Follow‐up

1 Reddy, et al. JAMA. 2014 ;312(19): 1988‐1998.2 Reddy VY et al. Circulation. 2011; 123:417‐424.3 Holmes et al., JACC 2014,;4(1): 1‐11.4Boersma, L. V. A., et al. CCI (2015); 88(3): 460‐465.

* Majority of patients enrolled could not take anticoagulation and therefore contraindicated in the US per current labeling.

Procedural Success

Implant success defined as deployment and release of the device into the LAA; no leak ≥ 5 mm

* The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use.1 Boersma, L.et al. EHJ 2016;37(31): 2465.; 2 Reddy VY, Holmes DR, et al. JACC 2016; 69(3): 253-261.

~50% new operators

~70% new operators performed 50% of

procedures

Favorable Procedural Safety Profile: All Device and/or Procedure‐related Serious Adverse Events within 7 Days

9.9%

4.8%4.1% 4.1% 3.8%

2.8%

0%

2%

4%

6%

8%

10%

12%

PROTECT AF1st Half

PROTECT AF2nd Half

CAP PREVAIL CAP2 EWOLUTION*

Patients With Safety Event(%)

N=232 N=231 N=566 N=269 N=579 N=10191

~50% New Operators in PREVAIL

* The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use.1 Boersma, LVA.et al. EHJ 2016; 37(31): 2465.

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WATCHMAN™

*The performance and timing of TEE to re‐evaluate the LAA seal is left to physician discretion.Typical to patient treatment in U.S. clinical trials

Warfarin Cessation with WATCHMAN

92% 99%

45 Days

92% of patients were able to discontinue warfarin after 45 days, with 99% able to discontinue after 1 year3

1. Reddy, VY et al. Circulation. 2011;123:417‐424. 2 WATCHMAN FDA Panel Sponsor Presentation. Oct 2014.. 3 Holmes, DR et al. JACC 2014; 64(1):1‐12.

WATCHMAN Enables Patients to Discontinue Long‐term OAC

92%92%

99%

1 Year

EndoCATHOcclusion Balloon

FindrWIRZGuidewire System

LARIAT

Suture delivery device

TenSURE

Suture tightener SureCUTSuture cutter

SofTIP

Guide Cannula

LARIAT Procedure

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LARIAT Suture Delivery Device

• FDA Indications: The LARIAT Suture Deliver Device facilitates suture placement and knot tying for use in surgical applications where soft tissue are being approximated and/or ligated with a pre‐tied polyester suture

ACCESS DELIVER CAPTURE/CLOSE REMOVE

Standard techniques and technology for pericardial

and transseptal access are utilized for placement. The

.025” FindrWIRE & EndoCATH are positioned.

The SofTIP is oriented to the target and the .035”

FindrWIRE is delivered to connect to the .025”

FindrWIRE at the target. The LARIAT is then

advanced.

With the snare opened, the LARIAT is advanced

over the target and closed. After confirmation, the suture is released &

tightened.

All catheters are removed, reverse heparin and all that remains with the

patient is a small remnant of suture. Band-Aid

closure

PLACE Procedure PERMANENT LIGATION APPROXIMATION CLOSURE & EXCLUSION

PLACE Procedure

Bartus et al. Heart Rhythm 2011;8:188-193. Bartus et al. J Am Coll Cardiol 2012; epub.

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Katz, et al. JACC 2000;36:468‐71

• Spontaneous echo contrast or thrombus seen in incompletely ligated LAA in 9 of 18 (50%) patients

• 4 patients with incompletely ligated LAA had thromboembolic events

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AtriClip

LA Appendage AnatomyCactus (30%) Cauliflower (3%)

Chicken Wing (48%) Windsock (19%)

DiBiase et al. J Am Coll Cardiol 2012;60:531‐8.A – CT; B ‐ CMR

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Calkins et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

AF/LAA Collaborative Team Approach

• Team Members• EP, IC (structural heart interest), surgeon

• Individualize Patient• Ablation Strategy and/or device?• Are there contraindication to anticoagulation?• Arrhythmia management

• Ablation

• Other AF treatment

• Concomitant surgical needs• CABG

• Valve

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