Table 1: Studies characteristics and patient demographics.

FIX-HF-5 Pilot
[12]
FIX-CHF-4
[13]
(Group 1/Group 2)
FIX-HF-5
[20]
FIX-HF-5C
[21]

Year 2006200820112018

Sample Size (N) 49164428160

Patients Withdrawn05 (group 1)
4 (group 2)
17 (OMT)
6 (CCM)
3 (OMT)
1 (CCM)

Study DesignCCM to all patients, 25 active CCM vs 24 inactive CCMCrossover Study: CCM to all patients; Group 1 (N=80; CCM first 3 months), Group 2 (N=84; sham first 3 months)CCM Implant (N = 215) vs OMT (N=213)CCM Implant (N = 74) vs OMT (N = 86)

Ejection Fraction Inclusion Criteria < 35%< 35%≤ 35%≥25% and ≤ 45%

Mean Follow up 6 months6 months6 months (noninferiority at 12 months)6 months

Outcomes NYHA Class, 6MWD, Stress Test, Holter MonitoringHolter Monitoring.
Changes in peak VO2, MLHFQ, and 6MWD at the end of 12 and 24 weeks.
Ventilatory anaerobic threshold, peak O2, MLHFQ, non-inferiority based on mortality and hospitalization with 12.5% allowable delta (12 months)Peak VO2, MLWHFQ, NYHA Class, 6MWD, safety assessed by percentages of patients free of device-related events.

Study Centers Single Center – Lone Star Arrhythmia and Heart Failure Center - TexasSingle Center - Germany50 US Centers
42 Centers (US, Germany, and Czechia).

Mean age (CCM/OMT)52 ± 15.0
59.6 ± 12.0
58.9 ± 9.8
59.9 ± 10
58.09 ± 12.79
58.55 ± 12.33
63 ± 11
63 ± 11

Male (CCM/OMT)68%/71%88.8%/81%73.5%/70.9%73%/79.1%

SBP (mmHg) (CCM/OMT)118.6 ± 19.7
115 ± 20.6
114.7 ± 17.0
117.1± 17.9
116.65 ± 19.48
115.61 ± 17.61
123 ± 18
126 ± 19

QRS Duration (msec) (CCM/OMT)109.2 ± 15.8
101.3 ± 14.2
119.9 ± 28.3
116.3 ± 26.6
101.63 ± 15.30
101.51 ± 12.81
103 ± 13.0
103.6 ± 12.1

ICD/Pacemaker (CCM/OMT)88% (22)
83% (20)
68.3% (55)
59.4% (50)
96% (207/215)
95% (202/213)
87.8% (65/74)
84.9% (73/86)

6MWD Baseline (m) (CCM/OMT)321
352 ± 95.4
386 ± 103
394 ± 102
326.38 ± 82.10
323.99 ± 92.44
317 ± 88
324 ± 90

NYHA Class IncludedIII and IVII and IIIIII and IVIII and IV

NYHA Class III (CCM/OMT)100%
96%
72.5%
80%
91.16%
85.92%
86.5%
90.7%

Ischemic Cardiomyopathy (CCM/OMT)64%
67%
63.8%
56%
64.7%
66.7%
62.2%
59.3%

Baseline LVEF () (CCM/OMT)24.9 ± 6.5
31.4 ± 7.4
29.3 ± 6.6
29.8 ± 7.8
25.74 ± 6.60
26.09 ± 6.54
33 ± 6
33 ± 5

Ventilatory Anaerobic Threshold (VAT) (CCM/OMT)10.6 ± 2.4
12.3 ± 2.5
Not documented10.95 ± 2.24
10.97 ± 2.18
Not documented

Peak O2 Consumption (CCM/OMT)14.3 ± 2.8
16.0 ± 2.9
14.1 ± 3.0
13.6 ± 2.7
14.74 ± 3.06
14.71 ± 2.92
15.5 ± 2.6
15.4 ± 2.8

OMT: optimal medical therapy, CCM: cardiac contractility modulation, 6MWD: 6-minute walking distance, MLWHFQ: Minnesota Living with Heart Failure Questionnaire, SBP: systolic blood pressure, SD: standard deviation, LVEF: left ventricular ejection fraction, and VAT: ventilatory anaerobic thresholds.