TABLE 1.
Summary of Prospective Clinical Trials of Autonomic Modulation in Humans
| Modality | Clinical Trial | Design | Patient Population | n | Outcome |
|---|---|---|---|---|---|
| Atrial arrhythmias | |||||
| Vagus nerve stimulation | Stavrakis et al. (51) | Randomized sham-controlled trial | Patients undergoing cardiac surgery | 54 | Decreased incidence of post-operative AF |
| Tragus stimulation | Stavrakis et al. (55) | Randomized sham-controlled trial | Patients with paroxysmal AF undergoing EP study | 40 | Decreased inducible AF duration during EP study |
| TREAT AF (56) | Randomized sham-controlled trial | Paroxysmal AF | 53 | Decreased AF burden at 6 months | |
| Renal denervation | Pokushalov et al. (63) | Randomized open-label trial | Paroxysmal or persistent AF and resistant hypertension | 27 | Decreased recurrence of any atrial tachyarrhythmia at 3 months |
| AFFORD (64) | Single-arm feasibility trial | Paroxysmal or persistent AF and hypertension | 20 | Decreased AF burden at 12 months | |
| ERADICATE AF (65) | Randomized open-label trial | Paroxysmal AF undergoing AF ablation | 302 | Increased freedom from AF, flutter, or tachycardia recurrence at 12 months | |
| Ventricular arrhythmias | |||||
| Vagus nerve stimulation | De Ferrari et al. (87) | Single-arm open-label trial | Systolic heart failure, NYHA functional class II or III, LVEF ≤35% | 32 | Significant improvement in NYHA functional class, quality of life, 6-min walk distance |
| ANTHEM HF (91) | Randomized open-label trial | Systolic heart failure, NYHA functional class II or III, LVEF ≤40% | 60 | Significant improvement in LVEF, HRV, NYHA functional class | |
| NECTAR HF (90) | Randomized single-blind trial | Systolic heart failure, NYHA functional class II or III, LVEF ≤35% | 96 | No significant change in LVESV or LVEF at 6 months | |
| INOVATE HF (89) | Randomized open-label trial | Systolic heart failure, NYHA functional class III, LVEF ≤40% | 707 | No significant difference in all-cause mortality or worsening heart failure | |
| Tragus stimulation | Yu et al. (97) | Randomized sham-controlled trial | Patients with ST-segment elevation myocardial infarction | 95 | Decreased ventricular arrhythmias within 24 h |
| Renal denervation | Symplicity HF (99) | Single-arm feasibility trial | Systolic heart failure, NYHA functional class III, LVEF <40%, renal impairment | 39 | Decreased NT-proBNP at 12 months |
| Spinal cord stimulation | SCS HEART (106) | Nonrandomized open-label trial | Systolic heart failure, NYHA functional class III, LVEF ≤35% | 22 | Improved NYHA functional class, LVEF, exercise capacity, quality of life |
| DEFEAT HF (107) | Randomized single-blind trial | Systolic heart failure, NYHA functional class III, LVEF ≤35% | 66 | No difference in incidence of ventricular arrhythmias | |
| Baroreceptor activation therapy | HOPE4HF (113) | Randomized open-label trial | Systolic heart failure, NYHA functional class III, LVEF ≤35% | 146 | Improved NYHA functional class, quality of life, exercise capacity, NT-proBNP |
AF = atrial fibtillation; AFFORD = Atrial fibrillation reduction by renal sympathetic denervation; ANTHEM HF = Autonomic Regulation Therapy for the Improvement of Left Ventricular Function and Heart Failure Symptoms; DEFEAT-HF = Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Systolic Heart Failure; ERADICATE AF = Effect of Renal Denervation and Catheter Ablation vs Catheter Ablation Alone on Atrial Fibrillation Recurrence Among Patients With Paroxysmal Atrial Fibrillation and Hypertension; HRV = heart rate variability; LVEF = left ventricular ejection fraction; LVESV = left ventricular end systolic volume; NECTAR HF = NEural Cardiac TherApy foR Heart Failure; HOPE4HF = Hope for Heart Failure; NT-proBNP=N-terminal B-type natriuretic peptide; NYHA = New York Heart Association; SCS HEART = Spinal Cord Stimulation for Heart Failure as a Restorative Treatment; Symplicity HF = Renal Denervation in Patients With Chronic Heart Failure & Renal Impairment; TREAT AF = Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation.