Temporal trends in characteristics and outcomes of patients undergoing percutaneous mitral valve repair

Table 1 Baseline characteristics, mean ±SD, n (%)

Variable	Pooled real-life variables	EVEREST program, population size	EVEREST vs pooled variable, MD or OR (95%CI)	COAPT trial, population size	COAPT vs pooled variable, MD or OR (95%CI)	MITRA-FR trial, population size	MITRA-FR vs pooled variable, MD or OR (95%CI)
First five-year period
Age (year)	71.99 ± 0.16; Q = 3.32	73.3 ± 10.5 (n = 616)	1.40 (0.57-2.23)	71.7 ± 11.8 (n = 302)	-0.20 (-1.53 to 1.13)	70.1 ± 10.1 (n = 152)	-1.80 (-3.41 to -0.19)
Male	67.5% (62.4-72.5); I2 = 97	364/616 (59.1)	0.97 (0.82-1.15)	201/302 (66.6)	1.33 (1.04-1.71)	120/152 (78.9)	2.51 (1.69-3.73)
Diabetes mellitus	33.9% (30.2-37.6); I2 = 79	239/616 (38.8)	1.20 (1.01-1.43)	106/302 (35.1)	1.03 (0.80-1.31)	50/152 (32.9)	0.93 (0.66-1.31)
Non-ischemic etiology	35.3 (30.8-40.0); I2 = 57	407/615 (66.2)	3.59 (2.92-4.42)	118/302 (39.1)	1.18 (0.91-1.53)	57/152 (37.5)	1.10 (0.77-1.56)
Prior myocardial infarction	41.9% (35.9-48.0); I2 = 84	334/602 (55.5)	1.89 (1.58-2.26)	156/302 (51.7)	1.62 (1.27-2.06)	75/152 (49.3)	1.48 (1.06-2.05)
Prior percutaneous coronary intervention	42.3% (35.9-48.9); I2=95	292/615 (47.5)	1.20 (1.01-1.43)	130/302 (43.0)	1.00 (0.79-1.27)	71/152 (46.7)	1.16 (0.84-1.61)
Atrial fibrillation	51.7% (46.2-57.1); I2 = 92	359/552 (65.0)	1.71 (1.42-2.06)	173/302 (57.3)	1.24 (0.98-1.57)	49/142 (34.5)	0.49 (0.34-0.69)
Renal insufficiency	46.1% (35.4-56.9); I2 = 98	163/616 (26.5)	0.38 (0.31-0.46)	214/299 (71.6)	2.66 (2.05-3.45)	22/152 (14.5)	0.18 (0.11-0.28)
ACEI/ARB	69.8% (64.4-74.9); I2 = 57	390/616 (63.3)	0.72 (0.58-0.90)	204/302 (71.9)	0.87 (0.66-1.16)	111/152 (82.2)	1.13 (0.77-1.67)
Beta-blocker	84.3% (79.5-88.6); I2 = 77	491/616 (79.7)	0.98 (0.78-1.24)	275/302 (91.1)	2.54 (1.68-3.85)	134/152 (88.2)	1.86 (1.12-3.09)
Diuretics	90.4% (87.7-92.8); I2 = 51	543/616 (88.1)	0.98 (0.98-1.31)	270/302 (89.4)	1.11 (0.74-1.65)	151/152 (99.3)	19.81 (2.75-142.48)
Oral anticoagulation agents	50.0% (23.5-77.3); I2 = 95	253/616 (41.1)	0.87 (0.66-1.15)	140/302 (46.4)	1.08 (0.78-1.48)	93/152 (61.2)	1.97 (1.32-2.92)
ICD device	30.1% (21.7-39.2); I2 = 91	170/600 (28.3)	0.92 (0.75-1.12)	91/302 (30.1)	1.00 (0.77-1.30)	48/151 (31.8)	1.08 (0.76-1.55)
Any cardiac device	49.4% (38.6-60.1); I2 = 96	170/600 (28.3)	0.41 (0.33-0.49)	206/302 (68.1)	2.20 (1.71-2.84)	94/151 (62.3)	1.69 (1.21-2.37)
Second five-year period
Age (year)	73.10 ± 0.24; Q = 3.66	73.3 ± 10.5 (n = 616)	0.20 (-0.63 to 1.03)	71.7 ± 11.8 (n = 302)	-1.40 (-2.73 to -0.07)	70.1 ± 10.1 (n = 152)	-3.00 (-4.61 to -1.39)
Male	66.5% (63.4-69.6); I2 = 56	364/616 (59.1)	0.69 (0.58-0.83)	201/302 (66.6)	0.95 (0.74-1.23)	120/152 (78.9)	1.80 (1.21-2.68)
Diabetes mellitus	30.8% (27.2-34.4); I2 = 56	239/616 (38.8)	1.32 (1.10-1.58)	106/302 (35.1)	1.12 (0.87-1.44)	50/152 (32.9)	1.02 (1.02-1.44)
Non-ischemic etiology	48.3% (38.1-58.6); I2 = 70	407/615 (66.2)	2.18 (1.66-2.86)	118/302 (39.1)	0.71 (0.52-0.98)	57/152 (37.5)	0.67 (0.45-0.99)
Prior myocardial infarction	24.9% (18.3-32.0); I2 = 79	334/602 (55.5)	3.03 (2.51-3.66)	156/302 (51.7)	2.60 (2.03-3.33)	75/152 (49.3)	2.37 (1.70-3.31)
Prior percutaneous coronary intervention	38.6% (32.7-44.7); I2 = 62	292/615 (47.5)	1.53 (1.24-1.89)	130/302 (43.0)	1.28 (0.98-1.67)	71/152 (46.7)	1.49 (1.05-2.10)
Atrial fibrillation	58.1% (51.2-64.8); I2 = 91	359/552 (65.0)	1.40 (1.16-1.69)	173/302 (57.3)	1.01 (0.79-1.28)	49/142 (34.5)	0.40 (0.28-0.57)
Renal insufficiency	47.8% (41.2-54.4); I2 = 67	163/616 (26.5)	0.35 (0.28-0.42)	214/299 (71.6)	2.41 (1.85-3.15)	22/152 (14.5)	0.16 (0.10-0.26)
ACEI/ARB	78.1% (72.4-83.3); I2 = 71	390/616 (63.3)	0.46 (0.37-0.58)	204/302 (71.9)	0.56 (0.42-0.74)	111/152 (82.2)	0.72 (0.49-1.07)
Beta-blocker	87.2% (84.5-89.6); I2 = 49	491/616 (79.7)	0.67 (0.53-0.85)	275/302 (91.1)	1.74 (1.15-2.64)	134/152 (88.2)	1.27 (0.77-2.12)
Diuretics	92.4% (89.8-94.8); I2 = 61	543/616 (88.1)	0.61 (0.45-0.82)	270/302 (89.4)	0.69 (0.46-1.03)	151/152 (99.3)	12.38 (1.72-89.08)
Oral anticoagulation agents	56.3% (26.7-83.7); I2 = 92	253/616 (41.1)	0.48 (0.35-0.66)	140/302 (46.4)	0.60 (0.42-0.85)	93/152 (61.2)	1.09 (0.71-1.67)
ICD device	33.9% (24.1-44.4); I2 = 87	170/600 (28.3)	0.89 (0.71-1.12)	91/302 (30.1)	0.97 (0.73-1.29)	48/151 (31.8)	1.05 (0.72-1.52)
Any cardiac device	48.8% (34.8-62.9); I2 = 96	170/600 (28.3)	0.46 (0.38-0.56)	206/302 (68.1)	2.49 (1.93-3.21)	94/151 (62.3)	1.91 (1.36-2.68)

EVEREST: Endovascular Valve Edge-to-Edge Repair Study; COAPT: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation; MITRA-FR: Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation; 95%CI: 95% confidence interval; ACEI/ARB: Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers; ICD: Implantable cardioverter-defibrillator; MD: Mean difference; OR: Odds ratio.

Table 2 Hospital presentation and echocardiographic parameters, mean ±SD, n (%)

Variable	Pooled real-life variables	EVEREST program, population size	EVEREST vs pooled variable, MD or OR (95%CI)	COAPT trial, population size	COAPT vs pooled variable, MD or OR (95%CI)	MITRA-FR trial, population size	MITRA-FR vs pooled variable, MD or OR (95%CI)
First five-year period
NYHA II	10.5 (7.2-14.2); I2 = 84	107/615 (17.4)	1.60 (1.26-2.02)	129/302 (42.7)	5.66 (4.40-7.28)	56/152 (36.8)	4.43 (3.13-6.26)
NYHA III	24.9 (18.3-32.0); I2 = 79	387/615 (62.9)	4.13 (3.41-5.00)	154/302 (50.9)	2.53 (1.98-3.24)	82/152 (53.9)	2.85 (2.04-3.98)
NYHA IV	23.3 (18.9-27.9); I2 = 84	108/615 (17.6)	0.77 (0.62-0.96)	18/302 (5.9)	0.23 (0.14-0.37)	14/152 (9.2)	0.37 (0.21-0.64)
NYHA III/IV	89.8 (86.2-92.9); I2 = 87	495/615 (80.5)	0.60 (0.48-0.75)	172/302 (57.0)	0.19 (0.15-0.25)	96/152 (63.1)	0.25 (0.18-0.35)
MR grade 3+	40.5% (31.3-50.0); I2 = 97	355/616 (58.1)	2.21 (1.86-2.63)	148/302 (49.0)	0.95 (0.74-1.22)	46/123 (37.4)	0.97 (0.67-1.41)
MR grade 4+	60.8% (52.4-68.9); I2 = 96	139/616 (22.7)	0.17 (0.14-0.20)	154/302 (51.0)	0.59 (0.47-0.75)	76/123 (61.8)	0.92 (0.64-1.34)
LVEDV (ml)	177.34 ± 1.22; Q = 7.73	162.2 ± 52.8 (558)	-15.10 (-19.48 to -10.72)	194.4 ± 69.2 (n = 302)	17.10 (9.30-24.90)	258.8 ± 71.11 (n = 152)	80.70 (69.40-92.00)
LVEF (%)	25.81 ± 0.22; Q = 50.71	43.2 ± 11.7 (558)	17.40 (16.43-18.37)	31.3 ± 9.1 (n = 302)	5.50 (4.47-6.53)	33.3 ± 6.5 (n = 152)	7.50 (6.47-8.53)
Second five-year period
NYHA II	11.2 (5.4-18.6); I2 = 93	107/615 (17.4)	1.11 (0.87-1.41)	129/302 (42.7)	3.93 (3.03-5.09)	56/152 (36.8)	3.07 (2.16-4.37)
NYHA III	68.9 (60.4-76.8); I2 = 90	387/615 (62.9)	0.88 (0.72-1.08)	154/302 (50.9)	0.54 (0.42-0.70)	82/152 (53.9)	0.61 (0.43-0.85)
NYHA IV	21.8 (14.6-29.9); I2 = 86	108/615 (17.6)	0.69 (0.54-0.89)	18/302 (5.9)	0.21 (0.13-0.34)	14/152 (9.2)	0.33 (0.19-0.58)
NYHA III/IV	90.6 (84.1-95.7); I2 = 94	495/615 (80.5)	0.69 (0.55-0.87)	172/302 (57.0)	0.22 (0.17-0.29)	96/152 (63.1)	0.29 (0.20-0.41)
MR grade 3+	57.3 (37.6-75.8); I2 = 98	355/616 (58.1)	2.27 (1.90-2.73)	148/302 (49.0)	1.61 (1.26-2.04)	46/123 (37.4)	1.00 (0.69-1.45)
MR grade 4+	57 (36.3-76.5); I2 = 98	139/616 (22.7)	0.15 (0.13-0.19)	154/302 (51.0)	0.55 (0.43-0.70)	76/123 (61.8)	0.86 (0.59-1.25)
LVEDV (ml)	155.38 ± 0.31; Q = 8.26	162.2 ± 52.8 (558)	6.80 (2.42-11.18)	194.4 ± 69.2 (n = 302)	39.00 (31.20-46.80)	258.8 ± 71.11 (n = 152)	102.60 (91.30-113.90)
LVEF	35.15 ± 0.17; Q = 15.97	43.2 ± 11.7 (558)	8.00 (7.03-8.97)	31.3 ± 9.1 (n = 302)	-3.90 (-4.93, -2.87)	33.3 ± 6.5 (n = 152)	-1.90 (-2.93 to -0.87)

¹136.2 ± 37.4 mL/m² converted to mL using 1.9 m².

EVEREST: Endovascular Valve Edge-to-Edge Repair Study; COAPT: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation; MITRA-FR: Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation; 95%CI: 95% confidence interval; ACEI/ARB: Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers; ICD: Implantable cardioverter-defibrillator; MD: Mean difference; OR: Odds ratio; LVEF: Left ventricular ejection fraction; LVEDV: Left ventricular end-diastolic volume; MR: Mitral regurgitation; NYHA: New York Heart Association.

Table 3 Procedural and clinical outcomes, mean ±SD, n (%)

Variable	Pooled real-life variables	EVEREST program, population size	EVEREST vs pooled variable, MD or OR (95%CI)	COAPT trial, population size	COAPT vs pooled variable, MD or OR (95%CI)	MITRA-FR trial, population size	MITRA-FR vs pooled variable, MD or OR (95%CI)
First five-year period
Post procedure
One device implanted	50.6 (41.2-60.0); I2 = 92	-	-	106/293 (36.2)	0.78 (0.61-1.00)	63/138 (45.7)	0.83 (0.59-1.18)
Two devices implanted	42.4 (35.2-49.8); I2 = 88	-	-	157/293 (53.6)	1.56 (1.22-1.99)	62/138 (44.9)	1.10 (0.78-1.56)
Three or more devices implanted	4.2 (2.9-5.7); I2 = 14	-	-	24/293 (8.2)	1.96 (1.19-3.21)	13/138 (9.4)	2.28 (1.21-4.29)
MR grade 1+	56.1 (48.5-63.5); I2 = 90	307/589 (52.1)	0.82 (0.69-0.98)	214/260 (82.3)	3.51 (2.53-4.86)	54/123 (43.9)	0.59 (0.41-0.85)
MR grade 2+	39.5 (33.0-46.2); I2 = 87	215/589 (36.5)	1.02 (0.84-1.22)	33/260 (12.7)	0.26 (0.18-0.37)	23/123 (18.7)	0.41 (0.26-0.64)
MR grade ≤ 2+	93.2 (89.6-96.2); I2 = 90	523/589 (88.8)	0.58 (0.44-0.78)	247/260 (95.0)	1.40 (0.79-2.48)	115/123 (93.5)	1.06 (0.71-2.19)
MR grade ≥ 3+	8.2 (5.4-11.6); I2 = 87	66/589 (11.2)	1.43 (1.07-1.91)	13/260 (5.0)	0.60 (0.34-1.06)	8/123 (6.25)	0.79 (0.38-1.64)
At follow-up
NYHA I/II at 12 months	74.4 (68.6-79.9); I2 = 77	511/616 (83.0)	1.74 (1.38-2.19)	171/237 (72.2)	0.931 (0.69-1.25)	76/112 (67.8)	0.76 (0.50-1.13)
MR grade ≤ 2+ at 12 months	85.1 (79.7-89.8); I2 = 88	349/413 (84.5)	1.20 (0.90-1.60)	199/210 (94.8)	3.98 (2.15-7.37)	79/97 (81.4)	0.97 (0.57-1.63)
All-cause mortality within 12 months	20 (15.7-24.6); I2 = 74	138/616 (22.4)	1.15 (0.92-1.44)	57/302 (19.1)	0.92 (0.68-1.26)	37/152 (24.3)	1.28 (0.87-1.89)
Second five-year period
Post procedure
One device implanted	46.6 (40.6-52.5); I2 = 86	-	-	106/293 (36.2)	0.74 (0.57-0.95)	63/138 (45.7)	1.09 (0.77-1.55)
Two devices implanted	46.9 (43.2-50.7); I2 = 64	-	-	157/293 (53.6)	1.22 (0.96-1.56)	62/138 (44.9)	0.86 (0.61-1.22)
Three or more devices implanted	6.3 (3.2-10.2); I2 = 81	-	-	24/293 (8.2)	1.04 (0.66-1.62)	13/138 (9.4)	1.21 (0.67-2.19)
MR grade 1+	57.7 (49.4-65.7); I2 = 82	307/589 (52.1)	0.65 (0.54-0.78)	214/260 (82.3)	2.76 (1.98-3.84)	54/123 (43.9)	0.46 (0.32-0.67)
MR grade 2+	24.9 (18.3-32.0); I2 = 79	215/589 (36.5)	1.40 (1.15-1.70)	33/260 (12.7)	0.35 (0.24-0.52)	23/123 (18.7)	0.56 (0.35-0.89)
MR grade ≤ 2+	89.7 (82.6-95.3); I2 = 90	523/589 (88.8)	0.60 (0.44-0.81)	247/260 (95.0)	1.43 (0.80-2.56)	115/123 (93.5)	1.08 (0.52-2.26)
MR grade ≥ 3+	11.4 (2.9-23.6); I2 = 90	66/589 (11.2)	1.38 (0.97-1.96)	13/260 (5.0)	0.57 (0.31-1.05)	8/123 (6.25)	0.76 (0.36-1.62)
At follow-up
NYHA I/II at 12 months	75.1 (56.6-90.0); I2 = 93	511/616 (83.0)	1.54 (1.16-2.03)	171/237 (72.2)	0.82 (0.58-1.15)	76/112 (67.8)	0.76 (0.43-1.03)
MR grade ≤ 2+ at 12 months	87.4 (81.1-92.6); I2 = 83	349/413 (84.5)	0.73 (0.52-1.02)	199/210 (94.8)	2.41 (1.27-4.58)	79/97 (81.4)	0.58 (0.34-1.02)
All-cause mortality within 12 months	18.1 (11.5-25.8); I2 = 86	138/616 (22.4)	1.14 (0.90-1.46)	57/302 (19.1)	0.92 (0.67-1.28)	37/152 (24.3)	1.28 (0.85-1.91)

EVEREST: Endovascular Valve Edge-to-Edge Repair Study; COAPT: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation; MITRA-FR: Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation; 95%CI: 95% confidence interval; MD: Mean difference; OR: Odds ratio; LVEF: Left ventricular ejection fraction; LVEDV: Left ventricular end-diastolic volume; MR: Mitral regurgitation; NYHA: New York Heart Association; NYHA: New York Heart Association.