Table 3.
Gene therapies for bradyarrhythmias
| Vector | Delivery technique | Genetic information | Species | Target | Outcomes | |
|---|---|---|---|---|---|---|
| Miake et al., 2002 | adenovirus | injection into LV cavity + transient cross clamping of great vessels | mutant Kir2.1AAA | guinea pig | VM | spontaneous pacemaker activity in vitro, ↑ ventricular rate on ECG |
| Qu et al., 2003 | adenovirus | intramyocardial injection after TT | murine HCN2 | dog | LA appendage | ↑ If, ↑ escape rhythm during VS |
| Plotnikov et al., 2004 | adenovirus | percutaneous intramyocardial injection | murine HCN2 | dog | LBB | ↑ If, ↑ escape rhythm during VS |
| Bucchi et al., 2006 | adenovirus | percutaneous intramyocardial injection | murine HCN2 or HCN2 E324A | dog | LBB | ↑ HR, ↓ PMI (HCN2E324A = HCN2), ↑ AR (HCN2E324A > HCN2) |
| Tse et al., 2006 | adenovirus | intramyocardial injection after TT | mutant murine HCN1ΔΔΔ | guinea pig; swine | VM; LA appendage | spontaneous PM activity in vitro & ex vivo, ↑ HR & ↓ PMI in SSS |
| Plotnikov et al., 2008 | adenovirus | percutaneous intramyocardial injection | murine HCN2 or chimeric HCN212 | dog | LBB | VT (with HCN212) |
| Ruhparwar et al., 2010 | adenovirus | intramyocardial injection after TT | murine AC6 | swine | VM | creation of escape rhythm in cAVB |
| Boink et al., 2012 | adenovirus | percutaneous intramyocardial injection | HCN2 (murine) and/or AC1 | dog | LBB | cAVB: ↓ PMI (HCN2+AC1, AC1 > HCN2), ↑ HR (HCN2+AC1 > AC1, HCN2), excessive HR with HCN2+AC1 |
| Cingaloni et al., 2012 | adenovirus | intramyocardial injection after TT percutaneous via venous catheter | murine HCN2 or/and Kir2.1AAA | swine | VM; AV junction | ↑ HR & ↓ PMI in cAVB |
| Boink et al., 2013 | adenovirus | percutaneous intramyocardial after TT | murine HCN2 or/and rat SkM1 | dog | LBB or VM | cAVB: no PMI in HCN2+SkM1, ↑ HR (HCN2+SkM1 > HCN2 or SkM1), ↑ AR & ↑ circadian rhythm modulation (HCN2+SkM1 > HCN2 or SkM1 alone) |
| Hu et al., 2014 | adenovirus | percutaneous intramyocardial injection via venous catheter | human TBX18 | swine | upper posteroseptal RV | In cAVB: creation of PM cells, ↑ HR, ↓ PMI, ↑ autonomic response |
Study characteristics of gene therapy approaches for bradyarrhythmias. The origin of the exogensouly delivered genetic material is indicated if specified in the study. AR, adrenergic response; AV, atrioventricular; HR, heart rate; cAVB, complete atrioventricular block; ECG, electrocardiogram; LA, left atrium; LBB, left bundle branch; LV, left ventricle; PM, pacemaker; PMI, electronic pacemaker intervention; RV, right ventricle; VM, ventricular myocardium; SSS, sick sinus syndrome; TT, thoracotomy; VS, vagal stimulation; VT, ventricular tachycardia.