Preventing Cardiac Conduction Defects With Drug Therapy
What is the cardiac conduction system, and what happens when it has defects? The cardiac conduction system is a group of specialized cardiac muscle cells that are responsible for sending signals to the heart causing to contract. The main components of this system are the SA node, AV node, bundle of His, bundle branches, and Purkinje fibers. A cardiac conduction defect occurs as a result of alterations in cardiac conduction through any of the components of the system and is a serious and potentially life-threatening disorder necessitating a permanent pacemaker in some individuals. At present there is no effective way to treat conduction defects in patients with cardiomyopathies, or heart block, making the need for such breakthroughs important. To date, no drug therapy has shown the potential to treat these defects.
Recently, a secondary analysis of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed that in 21,004 persons, predominantly older men, 1114 developed a conduction defect of first-degree AV block, left anterior fascicular bock, complete or incomplete left bundle branch block, complete or incomplete right bundle branch block, or intraventricular conduction delay when assessed by serial electrocardiograms.1 Of the 1114, the most common was right bundle branch block, followed by left bundle branch block, and intraventricular conduction delay. When compared to the control antihypertensive chlorthalidone, the angiotensin-converting enzyme (ACE) inhibitor lisinopril was associated with a 19% reduction in conduction abnormalities, (HR = 0.81; 95% CI, 0.69 to 0.95; p = 0.01), whereas treatment with amlodipine or pravastatin did not show any association decrease in defects. Importantly, this effect occurred independent of blood pressure lowering, as chorthalidone was a more effective blood pressure lowering agent than lisinopril in the ALLHAT trial.2
The study is limited by several factors including a small effect size of only 1114 individuals, a retrospective analysis, and the lack of reporting of atrial fibrillation which is associated with atrial conduction slowing.3-4
Why an ACE inhibitor but not other treatments? The answer may lie in the negative trophic effects of ACE inhibitors, that through a reduction in angiotensin II levels, a decrease activation of extracellular signal-regulated protein kinase and decrease fibroblast proliferation may occur.5 From a clinical perspective, ACE inhibitors are far more effective than chorthalidone in reducing left ventricular mass over time.6 These pharmacological changes to the underlying physiology may potentially contribute to the prevention of conduction defects. Of course, further controlled research is clearly warranted to verify and uncover the potential mechanisms of this important finding.
Mark A. Munger, PharmD, FCCP, FACC, is a Professor of Pharmacotherapy and Adjunct Professor of Internal Medicine, at the University of Utah, where he also serves as the Associate Dean, Academic Affairs for the College of Pharmacy.
References:
1. Dewland TA, Soliman EZ, Davis BR, et al.; Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. Effect of antihypertensive and lipid-lowering treatment to prevent heart attack trail (ALLHAT) on conduction system disease. JAMA Intern Med. 2016;176(8):1085-1092.
2. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic; The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-2997.
3. Narayan SM, Baykaner T, Maron DJ. Can cardiac conduction system disease by prevented? JAMA Intern Med. 2016;176(8):1093-1094.
4. Lalani GG, Schricker A, Gibson M, Rostamian A, Krummen DE, Narayan SM. Atrial conduction slows immediately before the onset of human atrial fibrillation; a bi-atrial contact mapping study of transitions to atrial fibrillation. J Am Coll Cardiol. 2012;59(6):595-606.
5. Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: A meta-analysis. J Am Coll Cardiol. 2005;45(11):1832-1839.
