Download ONLINE APPENDIX Supplemental Table 1. Participating centers

ONLINE APPENDIX
Supplemental Table 1. Participating centers and recruitment numbers
Site Name
#
Subject
s
9
Enrolled
Study #
Site #
Location
Asklepios Klinik St. Georg
005
00002
Hamburg, Germany
Instituto Dante Pazzanese
de Cardiologia
005
00003
Sao Paolo, Brazil
8
Elisabeth Krankenhaus
005
00005
Essen, Germany
3
University Hospital Bonn
005
00006
Bonn, Germany
15
Sanatorio Italiano
007
00071
Asuncion, Paraguay
3
Angiographia de Occidente
007
00072
Cali, Colombia
14
Clinica CardioVID – Santa Maria
007
00073
Medellin, Colombia
2
National Institute of Cardiology
007
00074
Warsaw, Poland
5
Centrum Medical Center HCP
007
00075
Poznan, Poland
6
American Heart of Poland
007
00076
Bielsko-Biala, Poland
6
TOTALS
10
71
Supplemental Table 2. Detailed inclusion and exclusion criteria
Inclusion:
 Subject with chronic functional mitral regurgitation (FMR)
 Subject is ≥18 years old
 Documented symptoms of CHF (NYHA II-IV)
 Symptomatic despite stable (at least 30 day’s duration) optimal medical regimen
per applicable standard for subject’s heart failure stage and NHYA classification
 Symptomatic despite at least 90 days of treatment with CRT, if indicated (i.e., QRS
≥120 ms, LVEF ≤35%, etc.)
 In the opinion of the heart team (minimum of one thoracic surgeon, one
interventional cardiologist and one cardiologist) the subject is not eligible or
recommended for corrective intervention on the valve via a surgical approach;
 Left ventricular ejection fraction (LVEF) of  20% and < 45%
 Mitral regurgitation grade  2 with regurgitant volume > 30ml and EROA > 20mm2
 Subject has a mitral plane to apex dimension  5.0 cm
 Structurally normal mitral valve
 Left ventricular end diastolic diameter (LVEDD) ≥ 5.0 cm and ≤ 7.5 cm
Exclusion:
 Significant organic mitral valve pathology (e.g. rheumatic, myxomatous
degeneration, mitral valve prolapse or flail leaflets), moderate or severe valve
calcifications, ruptured or otherwise non-functional papillary muscles and/or
chordae tendinae.
 Previous mitral valve repair or mitral valve replacement
 Bio-prosthetic or mechanical aortic valve
 Endocarditis
 MI within the 30 days prior to the index procedure
 Known unstable angina within 30 days prior to index procedure
 Any PCI within 30 days prior to the index procedure
 CABG within 3 months prior to the index procedure
 Any planned PCI within 30 days post index procedure
 Planned CABG ≤ 6-months post-index procedure
 Subject with severe, multi-vessel coronary artery disease who cannot tolerate
sudden hemodynamic changes or acute hemoglobin drop
 Cardiogenic shock characterized by systolic pressure <80 mm Hg, or cardiac index
<1.8 liters/minute/m2, or intra-aortic balloon pump or intravenous inotropes are
needed to maintain a systolic pressure ≥80 mm Hg and a cardiac index ≥1.8
liters/minute/m2
 Subject with peripheral vascular disease or tortuosity that would prevent
percutaneous access with a 14 Fr introducer sheath or intervention with the Mitralign
system
 Cerebrovascular Accident (CVA) within the past 6 months
 Serum creatinine >2.5 mg/dL (or 221 µmol/L)
 Subject is on chronic kidney dialysis
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Anemia (Hb < 9 g/L)
Thrombocytopenia (platelet count <100,000/mm3) or thrombocytosis
(>750,000/mm3)
Bleeding disorders or hypercoaguable state
Active peptic ulcer or active gastrointestinal (GI) bleeding
Contraindication to therapy with aspirin, antiplatelets or anticoagulants
Contraindications to or subject’s refusal of blood transfusions
Known allergy to stainless steel or platinum iridium or polyester
Any prior true anaphylactic reaction to contrast agents; defined as known
anaphylactic or other non-anaphylactic allergic reactions to contrast agents that
cannot be adequately pre-medicated prior to the index procedure
Pregnant or lactating; or female of childbearing potential with a positive pregnancy
test 24 hours before any study related radiation exposure
Co-morbid condition(s) that, in the judgment of the Investigator, could limit the
subject’s ability to participate in the study, including compliance with follow-up
requirements, or that could impact the scientific integrity of the study
Life expectancy of less than 12 months
Subject has impaired judgment and/or is undergoing emergency treatment
Currently participating in another investigational drug or device study that has not
completed the primary endpoint or that clinically interferes with the endpoints of this
study.
Thrombus in left ventricle or left atrium
Echocardiographic evidence of congenital, pericardial or infiltrative heart disease
Suboptimal trans-thoracic echocardiographic (TTE) windows, leading to incomplete
quantification of FMR or anatomic assessment
Significant subvalvular trabecularization or muscle bridges
Subject with mitral stenosis
Subject with moderate or severe aortic or tricuspid stenosis and/or moderate or
severe aortic or tricuspid regurgitation
Supplemental Table 3. Definition of study endpoints.
Primary Endpoints
Safety:
Major adverse events (MAE) within 30 days post index procedure
MAE defined as occurrence of any of the following: Urgent mitral valverelated cardiac surgery/intervention, myocardial infarction, cardiac
tamponade, stroke, or device/procedure-related death.
Performance:
Freedom from the following at 6 months
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mitral valve-related cardiac surgery/intervention,
device and/or procedure-related death; and
an increase in ventricular diameter
Secondary Endpoints
Device success

Implantation and plication of at least one pair of pledgets and retrieval of all
non-implantable system components
Procedure success
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Device success and no MAE prior to hospital discharge
Clinical outcomes at discharge, 1, 6, 12, and 24 months post index procedure
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All-cause mortality
MI
Cardiac tamponade
Re-hospitalization for CHF and/or mitral valve-related cardiac
surgery/intervention
Stroke
Renal function
MAE
NYHA classification
MLHF (QOL Questionnaire)
6-Minute Walk Distance (6MWD)
Tenting area and distance
Left ventricular regurgitant fraction
Mitral annular diameter
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Left ventricular volumes and diameters
Hemodynamics
Effective regurgitant orifice area (EROA)
Vena contracta
Coaptation
MR grade
Supplemental Table 4. Reasons for incomplete plication procedures.
20 subjects resulted in only a single plication.
16 of these subjects only had one set of pledgets implanted for the following reasons:
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8 anatomical challenges
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4 prolonged procedures > 3 hours
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2 procedure stopped for clinical event
(1 pericardial effusion, 1 ventricular fibrillation)
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1 fibrous annulus (difficulty crossing)
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1 incorrect positioning of the first pledget in second set
Four patients with two sets implanted had only one plication due to the following
reasons:
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2 single pledget annular detachment
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2 plications resulted in suboptimal valve changes (device locked without
plication)
Supplemental Table 5. Clinical outcomes and left ventricular remodelling of patients
with or without implants.
LVEDV mean
[ml]
6 MWD mean
[m]
MR Grade
mean
NYHA Grade
mean
30 Day Change
No Implant/
Plication (n)
Plication (n)
- 8.6 ± 35.5 (9)
-18.5 ± 31.0
(31)
17.9 ± 110.1 (9)
43.3 ± 115.0
(24)
-0.4 ± 1.2 (9)
-0.4 ± 1.1 (36)
-0.1 ± 0.6 (9)
0.0 ± 1.0 (38)
6 Months
No Implant/
Plication (n)
Plication (n)
-14.6 ± 36.1 (8)
-21.6 ± 28.6
(27)
69.4 ± 116.1 (5) 56.5 ± 92.0 (24)
-0.2 ± 1.3 (6)
-0.5 ± 1.2 (27)
-0.3 ± 0.7 (7)
-0.4 ± 0.7 (30)
LVEDV, left ventricular end-diastolic volume; 6MWD, six minute walking distances; MR, mitral
regurgitation; NYHA, New York Heart Failure classification.