Utility of Adenosine Sequelae in Primer Balloon Aortic Valvuloplasty

Aortic stenosis is an insidious disease with a long latency period.¹ Severe symptomatic aortic stenosis is associated with poor outcomes unless an aortic valve replacement procedure is performed.¹ In the real world, 30% of patients with severe symptomatic aortic stenosis do not undergo surgical aortic valve replacement because of advanced age, left ventricular dysfunction, or the presence of multiple comorbid conditions.² Since outcomes with medical management are uniformly poor, a less invasive and safer alternative to surgical aortic-valve replacement is needed for this expanding group of patients.³ Transcatheter aortic-valve implantation (TAVI) has emerged to be an attractive alternative in this cohort. The results of the PARTNER (Placement of AoRTic TraNscathetER Valve Trial) trial showed significant reduction in the all-cause mortality, the composite endpoint of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major stroke and major vascular events.⁴ Balloon aortic valvuloplasty (BAV) is the key step to get the valve “primed” prior to TAVI. The concept of cardiac standstill during these procedures has been used in the past to prevent cardiac contraction causing movement of the balloon during inflation, as that can lead to suboptimal results and potential damage.⁵ Balloon stability during the procedure is vital for a successful procedure and likely to minimize potential complications. However, cardiac contraction tends to push the balloon across the stenosed valve into the aorta. While surgeons use cardioplegia, fibrillators, or clamps to stop blood flow in their working field, most catheter interventions are performed on normal circulation. Rapid right ventricular pacing (RRVP) and adenosine have been used successfully with BAV for congenital aortic valve stenosis.^5,6 RRVP may trigger hypotension and may lead to decompensation in patients with systolic heart failure; hence, alternatives like adenosine have been tried. Adenosine has been used in the past to secure cardiac standstill for balloon dilatation of aortic and pulmonary valves, coarctation, and conduit stenosis in pediatric interventions. Adenosine has the advantage of being an innate product that is rapidly broken down by red blood cells and endothelium and has a half life of around 10 seconds. This guarantees a short period of asystole with a predictable return of spontaneous conduction. The duration of asystole is dose-dependent, but is also influenced by the rapidity and site of administration, as well as by cardiac output and possibly by drug interaction with dipyridmole, caffeine, etc.

In this issue of the Journal, Davidavicius et al⁷ report the findings of their study comparing the safety and feasibility of 24 vs 36 mg of adenosine during BAV. Twenty consecutive patients who underwent TAVI were randomized 1:1 to either bolus dose of 24 mg adenosine or 36 mg adenosine. The primary endpoint was successful valvuloplasty defined by complete balloon inflation and deflation across the aortic valve during the transient asystole induced by a single bolus of adenosine. The authors also investigated the incidence of ventricular ectopic beats during balloon inflation or deflation, balloon displacement requiring repositioning, and failure of adenosine to induce asystole. Standard practices as described earlier were used to perform BAV. The authors report a single bolus of adenosine induced atrioventricular (AV) block (mean duration, 18.6 ± 6.6 seconds) followed by cardiac asystole in 16 patients (80%) (low dose, n = 9).

A successful BAV was achieved in 12 patients (60%) (low dose, n = 8). Adenosine induced only bradycardia in 4 patients (20%) (low dose, n= 1). A burst of ventricular extra beat during BAV occurred in all patients. Balloon displacement occurred in 6 patients (37.5%). They report successful BAV was accomplished in 60% of patients. Authors propose adenosine infusion as a feasible alternative to RRVP in patients with high likelihood for decompensation with rapid pacing. They also report equal efficacy with low vs high-dose adenosine. No associated complications are reported with adenosine use. However, they acknowledge that the frequent occurrence of ventricular ectopic beats during transient asystole or partly from ventricular irritability secondary to hardware manipulation makes this approach unsuitable for balloon positioning. The authors investigated the previously tested role of adenosine for induction of hypotension in adult neurointerventional procedures and applied it during BAV. Although this has been used extensively for congenital aortic stenosis, its role in degenerative aortic stenosis has not been extensively investigated. The study reports no complication secondary to use of adenosine, which though impressive, could be due to a small sample size. The dose response of adenosine, however, is inconsistent both with respect to the onset and duration of asystole.⁵ Moreover, with adenosine, ventricular extra systoles cannot be controlled, leading to more robust ventricular contraction compared to a normal beat with potential for balloon movement and possible valvular damage. The response to adenosine will also differ in patients with “slick” AV node conduction or patients taking multiple AV node blocking agents. RRVP has the advantage over adenosine-induced ventricular asystole of being more predictable in timing and response, while inducing a shorter period of hypotension owing to the absence of ATP-induced vasodilatation. The term “fuzzy logic” has generally been relegated to a branch of mathematics, but this concept can now be figuratively applied to the refinement of TAVI procedure. Prospective, adequately powered, randomized trials are needed to determine if adenosine has any advantages over RRVP. This will also help us understand if a particular subgroup of patients may benefit from either method.

References

1. Ross J Jr, Braunwald E. Aortic stenosis. Circulation. 1968;38(1 Suppl):61-67.
2. Varadarajan P, Kapoor N, Bansal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006;82(6):2111-2115. 
3. Dewey TM, Brown D, Ryan WH, Herbert MA, Prince SL, Mack MJ. Reliability of risk algorithms in predicting early and late operative outcomes in high-risk patients undergoing aortic valve replacement. J Thorac Cardiovasc Surg. 2008;135(1):180-187. 
4. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597-1607.
5. De Giovanni JV, Edgar RA, Cranston A. Adenosine induced transient cardiac standstill in catheter interventional procedures for congenital heart disease. Heart. 1998;80(4):330-333.
6. Daehnert I, Rotzsch C, Wiener M, Schneider P. Rapid right ventricular pacing is an alternative to adenosine in catheter interventional procedures for congenital heart disease. Heart. 2004;90(9):1047-1050.
7. Davidavicius G, Chieffo A, Shannon J, et al. A high dose of adenosine to induce transient asystole for valvuloplasty in patients undergoing transcatheter aortic valve implantation (TAVI): is it a valid alternative to rapid pacing? A prospective pilot study. J Invasive Cardiol. 2011;23(11):467-471. 

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From the Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Address for correspondence: Rajesh Sachdeva, MD, 4300 W. 7th Street, Little Rock, AR 72205. Email: rrsachdeva@gmail.com