| Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access |
| Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc |
| Journal website https://www.cardiologyres.org |
Review
Volume 13, Number 1, February 2022, pages 11-17
Updates on Baroreflex Activation Therapy and Vagus Nerve Stimulation for Treatment of Heart Failure With Reduced Ejection Fraction
Tables
| Study | Device | Study size | Design | Duration | Main findings |
|---|---|---|---|---|---|
| BAT: baroreflex activation therapy; VNS: vagus nerve stimulation; HF: heart failure; LVEF: left ventricular ejection fraction; LVESD: left ventricular end systolic diameter; LVESV: left ventricular end systolic volume; MLHFQ: Minnesota Living with Heart Failure Questionnaire; MSNA: muscle sympathetic nerve activity; NYHA: New York Heart Association; 6MHWD: 6-minute hall-walk distance; MANCE: major adverse neurological and cardiovascular events; CRT: cardiac resynchronization therapy. | |||||
| Gronda et al, 2015 [8] | BAT | 11 | Prospective, nonrandomized, single center | 6, 21 months | BAT improved: |
| 1) MSNA: -13.6 ± 1.6 bursts/min; -15.0 ± 2.6 burst/min, P < 0.001 | |||||
| 2) Hospitalization rates: -1.31 ± 1.63 days/month; -1.17 ± 1.74 days/month, P < 0.01 | |||||
| 3) LVEF: +3.3±1.7%; +0.8±1.7%, P = 0.006 | |||||
| 4) 6MHWD: +69.7 ± 24.4 m; +58.4 ± 33.4 m, P = 0.01 | |||||
| 5) MLHFQ: -11.5 ± 4.6 points; -13.2 ± 5.4 points, P = 0.006 | |||||
| 6) NYHA: 73% of patients decreased by two classes | |||||
| Abraham et al, 2015 [10] | BAT | 146 | Multi-center randomized control trial | 6 months | BAT improved: |
| 1) Hospitalization rates: -0.49 ± 0.2 hospitalizations/patient/year, P ≤ 0.05 | |||||
| 2) 6MHWD: +59.6 ± 14.1 m, P < 0.001 | |||||
| 3) NYHA: 55% of patients decreased by one NYHA class | |||||
| Safety: 6-month MANCE-free rate = 85.9% | |||||
| Zile et al, 2015 [7] | BAT | 118 | Post-hoc analysis of multi-center randomized control trial | 6 months | BAT + no CRT improved: |
| 1) LVEF: +4.3±1.20%, P < 0.05 | |||||
| 2) 6MHWD: +85.5 ± 20.5 m, P < 0.05 | |||||
| 3) MLHFQ score: -21.6 ± 3.6 points, P < 0.05 | |||||
| 4) HF hospitalization rate: -0.53 ± 0.2 hospitalizations, P < 0.05 | |||||
| BAT + CRT improved: | |||||
| 1) MLHFQ: -9.3 ± 4.0 points, P < 0.05 | |||||
| Safety: 6-month MANCE-free rate 96-100% | |||||
| Dell’Oro et al, 2017 [9] | BAT | 7 | Prospective, nonrandomized single center long-term follow-up | 43 months | BAT improved: |
| 1) MSNA: -19.6 ± 4.4 bursts/min, P < 0.05 | |||||
| 2) Hospitalization rates: -9.29 ± 3.9 days/year/patient, P < 0.02 | |||||
| 3) LVEF: +4.4±5%, P < 0.05 | |||||
| 4) 6MHWD: +106.8 ± 58 m, P < 0.02 | |||||
| Premchand et al, 2014 [11] | VNS Cyberonics device | 60 | Open label multi-center, randomized uncontrolled feasibility trial | 6 months | VNS improved: |
| 1) LVEF: +4.5% (95% CI: 2.4 - 6.6) | |||||
| 2) 6MHWD: +56 m (95% CI: 37 - 75) | |||||
| 3) MLHFQ: -18 points (95% CI: -20 to -13) | |||||
| 4) NYHA: 77% of patients improved | |||||
| Adverse events: cough (n = 19), dysphonia (n = 13), and oropharyngeal pain at implant site (n = 8), embolic stroke (n = 1) | |||||
| Zannad et al, 2015 [13] | VNS Boston Scientific device | 99 | Multi-center randomized, sham-controlled trial | 6 months | VNS showed no significant improvement in: 1) LVEF; 2) LVESD; 3) LVESV |
| VNS improved: | |||||
| 1) NYHA: 62% of patients decreased by one NYHA class | |||||
| 2) MLHFQ: -7.7 points (CI -14.3 to -0.03), P = 0.049 | |||||
| Premchand et al, 2016 [12] | VNS Cyberonics device | 49 | Open label multi-center, randomized uncontrolled feasibility trial long-term follow-up | 12 months | VNS improved: |
| 1) LVEF: +6.3%, P < 0.005 | |||||
| 2) 6MHWD: +64 m, P < 0.005 | |||||
| 3) MLHFQ: -21 points, P < 0.005 | |||||
| 4) NYHA: 57% class II and 47% class III to 70% class I and 30% class II | |||||
| Adverse events: dysphonia, implant site pain, shoulder pain | |||||
| Gold et al., 2016 [15] | VNS Cardiofit device | 707 | Multi-center randomized, open-label controlled trial | 12 months | VNS failed to show reduction in rate of death or HF events in patients with chronic HF |
| De Ferrari et al, 2017 [14] | VNS Boston Scientific device | 91 | Open-label multi-center, randomized, uncontrolled feasibility trial follow-up | 18 months | VNS failed to show significant improvement in LVESD, the primary efficacy endpoint, or LVEF after long-term follow-up |
| Baseline characteristics | Age (years) | Sex (% male) | NYHA class III (%) | NYHA class II (%) | LVEF (%) | Patients on ICD (%) | Patients on CRT (%) |
|---|---|---|---|---|---|---|---|
| BAT: baroreflex activation therapy; VNS: vagus nerve stimulation; NYHA: New York Heart Association; LVEF: left ventricular ejection fraction; ICD: implantable cardioverter defibrillator; CRT: cardiac resynchronization therapy. | |||||||
| BAT (Gronda et al, 2015 [8]) | 67 ± 9 | 72.7 | 100 | - | 32.6 | 63.6 | - |
| BAT (Abraham et al, 2015 [10]) | 64 ± 11 | 87.3 | 98.6 | - | 24 | 88.7 | 33.8 |
| No BAT control (Abraham et al, 2015 [10]) | 66 ± 12 | 84.1 | 100 | - | 25 | 85.5 | 30.4 |
| BAT + CRT (Zile et al, 2015 [7]) | 68 ± 9 | 91.1 | 100 | - | 24 | 91.1 | - |
| BAT + no CRT (Zile et al, 2015 [7]) | 63 ± 12 | 83.2 | 98.2 | - | 25 | 85.3 | - |
| BAT (Dell’Oro et al, 2017 [9]) | 66.5 ± 3 | 85.7 | 100 | - | 33.2 | - | - |
| VNS (Premchand et al, 2014 [11]) | 51.5 ± 12.2 | 87 | 43 | 57 | 32.4 | 0 | 0 |
| VNS (Zannad et al, 2015 [13]) | 59.8 ± 12.2 | 89 | 81 | 11 | 30.5 | 81 | 8 |
| No-VNS control (Zannad et al, 2015 [13]) | 59.3 ± 10.1 | 81 | 69 | 22 | 30.8 | 69 | 13 |
| VNS (Premchand et al, 2016 [12]) | 52 ± 13 | 86 | 43 | 57 | 33 | 0 | - |
| VNS (Gold et al, 2016 [15]) | 61.7 ± 10.5 | 77.8 | 100 | - | 23.9 | 49.3 | 33.2 |
| No-VNS control (Gold et al, 2016 [15]) | 60.9 ± 11.2 | 80.8 | 100 | - | 25.2 | 46.9 | 35 |
| VNS (De Ferrari et al, 2017 [14]) | 59.8 ± 11.5 | 85 | 76 | 17.9 | 29.9 | 78 | 9 |