ACCESS-Europe A Two-Phase Observational Study of the MitraClip® System in Europe

MR Severity: Site-assessed mitral regurgitation severity using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 1+ to 2+ is mild-to-moderate, 2+ to 3+ is moderate to moderate-to-Severe, 3+ is moderate-to-severe, 3+ to 4+ is moderate-to-severe to severe, 4+ is severe. MR severity was not consistently captured for patients in the Medical Management and Mitral Valve Surgery groups. The Medical Therapy & Mitral Valve Surgery comparator groups were followed & studied primarily from a health economic perspective. Availability of clinical outcomes at follow-up is limited & has not been validated. Clinical outcomes for the comparator groups will not be reported.

Time frame: At 12 months

Population: MR severity was not consistently captured for patients in the Medical Management and Mitral Valve Surgery groups. MR severity will not be reported for these comparator arms. A total of 240 patients excluded from analysis population due to death:98, withdrew consent:58, lost to follow-up:22 and missed mitral regurgitation evaluation:62 at 12 months.

MR Severity: Site-assessed mitral regurgitation severity using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 1+ to 2+ is mild-to-moderate, 2+ to 3+ is moderate to moderate-to-Severe, 3+ is moderate-to-severe, 3+ to 4+ is moderate-to-severe to severe, 4+ is severe. MR severity was not consistently captured for patients in the Medical Management and Mitral Valve Surgery groups. The Medical Therapy & Mitral Valve Surgery comparator groups were followed & studied primarily from a health economic perspective. Availability of clinical outcomes at followup is limited & has not been validated. Clinical outcomes for the comparator groups will not be reported.

Time frame: At baseline

Population: MR severity was not consistently captured for patients in the Medical Management and Mitral Valve Surgery groups. MR severity will not be reported for these comparator arms. A total of 240 patients excluded from analysis population due to death:98, withdrew consent:58, lost to follow-up:22 and missed mitral regurgitation evaluation:62 at baseline.

This outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups. Because the Medical Therapy&Mitral Valve Surgery comparator groups were followed&studied primarily from a health economic perspective.Availability of clinical outcomes at follow-up is limited & has not been validated. Clinical outcomes for the comparator groups will not be reported.

Time frame: On day 1 post procedure

Population: 1-Day Post-Procedure Safety Outcomes are reported only for patients who underwent the MitraClip procedure. This outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups

The Minnesota Living with Heart Failure Questionnaire(MLHFQ) is comprised of 21 questions.The response for each question ranges from 0(no affect on the patient's living) to 5(affected the patient's life very much during the past month).The total score for the 21 items can range from 0-105.A lower&higher MLHFQ score indicates less effect of heart failure&the worse impact of heart failure on a patient's QOL,respectively.Although the MLHFQ incorporates relevant aspects of the key dimensions of QOL (physical and emotional),the questionnaire was not designed to measure any particular dimension separately.The total score should be taken as the best measure of how heart failure and treatments impact QOL. The total score is the sum of a)the physical dimension,measured using 8 questions (possible subscale score range 0-40) b)the emotional dimension,measured using 5 questions(possible subscale score from 0-25)&c) other factors,measured using 8 questions (possible subscale score from 0-40).

Time frame: 12 months

Population: The MLWHF Questionnaire was not consistently administered to patients in the Medical Management\&Mitral Valve Surgery groups.Thus MLWHF will not be reported for these comparator arms.Of the 567 MitraClip device patients,264 analyzed due to death:98,withdrew consent:58,lost to follow-up:22\&125 patients did not complete MLWHF Questionnaire.

Time frame: Day 0 (On the day of procedure)

Population: Contrast volume is reported only for patients who underwent the MitraClip procedure. This outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups.~Contrast volume was not recorded for 9 of 567 patients. Therefore, Contrast volume is available for 558 subjects.

Device embolization is defined as bilateral Clip detachment resulting in Clip embolization. Reasons for Clip embolization include leaflet tearing, Clip unlocking, Clip fracture or inadequate Clip placement (i.e., malposition). Not included are any fractures or other failures of the Clip that do not result in Clip detachment from both leaflets. Single leaflet device attachment (SLDA) is defined as the loss of insertion of a single leaflet from the MitraClip device with ongoing insertion of the opposing leaflet. SLDAs are reported on ACCESS-EU adverse event log and MitraClip procedure electronic case report forms, and may also be reported by Abbott Vascular personnel per EU Vigilance requirements.

Time frame: Through 12 months

Population: Device Embolization and Single Leaflet Device Attachment are reported only for patients who underwent the MitraClip procedure. This outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups.

Time frame: At discharge, an average of 7.7 days following the MitraClip procedure

Population: MR severity was not consistently captured for patients in the Medical Management and Mitral Valve Surgery groups.MR severity will not be reported for these comparator arms.~A total of 521 MitraClip patients analyzed.Missing data is due to death(n=11),patient withdrawal(n=13),data unavailable(n=3),discharge echocardiogram not done/missing(n=19).

Time frame: At discharge, an average of 7.7 days following the MitraClip procedure

Population: Discharge Status and Facility is reported only for patients who underwent the MitraClip procedure. This secondary outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups.Discharge Status and Facility outcomes data is available for 563 patients.

Time frame: Day 0 (On the day of procedure)

Population: Fluoroscopy duration is reported only for patients who underwent the MitraClip procedure. This outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups~Fluoroscopy duration was not recorded for 99 of 567 patients. Therefore, Fluoroscopy duration is available for 468 patients

ICU and hospital stay is defined as the mean duration of time that patients spent in the ICU (Intensive Care Unit)/ CCU (Cardiac Care Unit)/ PACU (Post-Anesthesia Care Unit) following the MitraClip procedure. This secondary outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups.

Time frame: From the day of procedure throughout 12 months of study period

Population: ICU and Hospital Stay is reported only for patients who underwent the MitraClip procedure.The Medical Therapy\&Mitral Valve Surgery comparator groups were followed\&studied primarily from a health economic perspective. Availability of clinical outcomes for the comparator groups is limited, thus it has not been validated and reported.

Time frame: At 6 months

Population: Kaplan-Meier freedom from all-cause mortality is not reported for the Medical Management or the Mitral Valve Surgery groups comparator groups. Since they were followed \& studied primarily from a health economic perspective. Availability of clinical outcomes for the comparator groups is limited, thus it has not been validated and reported.

Time frame: At 0 day

Population: Kaplan-Meier freedom from all-cause mortality is not reported for the Medical Management or the Mitral Valve Surgery groups comparator groups. Since they were followed\&studied primarily from a health economic perspective. Availability of clinical outcomes for the comparator groups is limited, thus it has not been validated and reported.

Time frame: At 30 days

Population: Kaplan-Meier freedom from all-cause mortality is not reported for the Medical Management or the Mitral Valve Surgery groups comparator groups. Since they were followed \& studied primarily from a health economic perspective. Availability of clinical outcomes for the comparator groups is limited, thus it has not been validated and reported.

Time frame: At 12 months

Population: Kaplan-Meier freedom from all-cause mortality is not reported for the Medical Management or the Mitral Valve Surgery groups comparator groups. Since they were followed \& studied primarily from a health economic perspective. Availability of clinical outcomes for the comparator groups is limited, thus it has not been validated and reported.

This end point is assessed on subjects who underwent mitral valve surgery within 12 months post-MitraClip procedure.

Time frame: Through 12 months

Population: This outcome measure is reported only for the MitraClip device group. The need for mitral valve surgery was not captured in the Medical Management or the Mitral Valve Surgery groups.

Physicians had the option of deploying more than 1 MitraClip device if a single device did not provide satisfactory MR reduction, and if the mitral valve area was large enough to allow multiple MitraClip devices to be placed without causing mitral stenosis.

Time frame: Day 0 (On the day of procedure)

Population: Number of MitraClip Devices Implanted is reported only for patients who underwent the MitraClip procedure.The Medical Therapy\&Mitral Valve Surgery comparator groups were followed\&studied primarily from a health economic perspective. Availability of clinical outcomes for the comparator groups is limited, thus it has not been validated and reported.

New York Heart Association (NYHA) Functional Classification. Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest.Ordinary physical activity results in fatigue, palpitation, dyspnea or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest.Less than ordinary physical activity causes fatigue, palpitation dyspnea or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort.Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest.If any physical activity is undertaken,discomfort is increased.

Time frame: At baseline

Population: NYHA Functional Class was not consistently captured for patients in the Medical Management\&Mitral Valve Surgery groups.NYHA Functional Class will not be reported for these comparator arms.A total of 567 MitraClip patients,343 analyzed due to death:98,withdrew consent:58,lost to follow-up:22,patients had missing NYHA Functional Class assessment:46 .

Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status. Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity.Patients are comfortable at rest.Ordinary physical activity results in fatigue, palpitation, dyspnea/anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity.They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea/anginal pain Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort.Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken,discomfort is increased.

Time frame: At 12 month

Population: NYHA Functional Class was not consistently captured for patients in the Medical Management\&Mitral Valve Surgery groups.NYHA Functional Class will not be reported for these comparator arms.Of total 567 MitraClip patients,343 analyzed due to death:98,withdrew consent:58,lost to follow-up:22,patients had missing NYHA Functional Class assessment:46 .

Procedure Time is defined as the time of start of the transseptal procedure to the time the Steerable Guide Catheter is removed.

Time frame: Day 0 (On the day of procedure)

Population: Procedure time is reported only for patients who underwent the MitraClip procedure. This outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups.~Procedure Time was not recorded for 196 of 567 patients.Therefore, the data is available for 371 patients.

The 6-minute walk distance test will be used to measure the patient's exercise capacity.

Time frame: 12 months

Population: The 6-MWT was not consistently captured for patients in the Medical Management\&Mitral Valve Surgery groups.Thus it will not be reported for these comparator arms.Of the 567 MitraClip device patients,216 analyzed due to death:98,withdrew consent:58,lost to follow-up:22\&173 patients did not perform the 6-minute walk test at the12 month visit.~.

The 6-minute walk distance test will be used to measure the patient's exercise capacity.

Time frame: Baseline

Population: The 6-minute walk test was not consistently captured for patients in the Medical Management\&Mitral Valve Surgery groups.Thus it will not be reported for these comparator arms.Of the 567 MitraClip device patients,216 analyzed due to death:98,withdrew consent:58,lost to follow-up:22\&173 patients did not perform the 6-minute walk test at baseline.~.

The 6 minute walk distance test will be used to measure the patient's exercise capacity. The change in 6 minute walk test distance is calculated as the difference between the distance walked at 12 months and the distanced walked at baseline.

Time frame: Baseline and 12 months

Population: The 6-minute walk test was not consistently captured for patients in the Medical Management\&Mitral Valve Surgery groups.Thus it will not be reported for these comparator arms.Of the 567 MitraClip device patients,216 analyzed due to death:98,withdrew consent:58,lost to follow-up:22\&173 patients did not perform the 6-minute walk test.~.