Publications

OBJECTIVES: The authors sought to study mechanisms to explain why single premature atrial complexes (PACs) from the pulmonary veins (PVs) may initiate human atrial fibrillation (AF).

BACKGROUND: Theoretically, single PACs may initiate AF if the rate response of action potential duration (APD) restitution has a slope >1. However, human left atrial APD restitution and its relationship to AF have not been studied. We hypothesized that an APD restitution slope >1 near PVs explains the initiation of clinical AF.

METHODS: We studied 27 patients with paroxysmal and persistent (n = 13) AF. We advanced monophasic action potential catheters transseptally to superior PVs. Restitution was plotted as APD of progressively early PACs against their diastolic interval (DI) from prior beats. Activation time restitution was measured using the time from the pacing artifact to each PAC.

RESULTS: Compared with paroxysmal AF, patients with persistent AF had shorter left atrial APD and effective refractory period (p = 0.01). In paroxysmal AF, maximum left atrial APD restitution slope was 1.5 +/- 0.4; and 12 of 13 patients had slope >1 (p < 0.001). In persistent AF, PACs encountered prolonged activation for a wider range of beats than in paroxysmal AF (p = 0.01), which prolonged DI and flattened APD restitution (slope 0.7 +/- 0.2; p < 0.001); no patient had APD restitution slope >1. A single PAC produced AF in 5 patients; in all, an APD restitution slope >1 caused extreme APD oscillations after the PAC, then AF.

CONCLUSIONS: In patients with paroxysmal AF, maximum APD restitution slope >1 near the PVs enables single PACs to initiate AF. However, patients with persistent AF show marked dynamic activation delay near PVs that flattens APD restitution. Studies should determine how regional APD and conduction dynamics contribute to the substrates of persistent AF.

Based on overwhelming data demonstrating reduced morbidity and mortality, ACE inhibitors form a mainstay of therapy in all patients with symptomatic left ventricular systolic dysfunction. Furthermore, ACE inhibitors may be beneficial in the prevention of heart failure in patients with high-risk cardiovascular profiles. However, definite benefit from the use of ACE inhibitors in all patients with heart failure and preserved ejection fraction has not been demonstrated. Even though ACE inhibitors probably have a class effect in patients who have heart failure, it is recommended that ACE inhibitors that have been shown to reduce morbidity and mortality in clinical trials (captopril, enalapril, lisinopril, and ramipril) be used because studies have clearly defined a dose for these agents that is effective in modifying the natural history of the disease. Attempts should be made to up titrate patients to target doses of ACE inhibitors that have been used in clinical trials, if tolerated.

Postsurveillance data should be systematically collected, timely, and publicly available

The lipid hypothesis, which was proposed over 100 years ago, is based on the premise that dyslipidemia is central to the process of atherosclerosis. Low-density lipoprotein and lipoprotein(a) are clearly atherogenic, whereas the role of very low-density lipoprotein as an independent factor is controversial. The only lipoprotein that is clearly antiatherogenic is high-density lipoprotein (HDL), which is thought to reduce coronary risk by mediating cholesterol efflux from the periphery by way of transportation to the liver for excretion. Traditionally, fibric acid derivatives and nicotinic acid were the major pharmacologic agents used to raise circulating levels of HDL. Recent therapeutic advances have been made in the ability to increase HDL. Apolipoprotein A-I Milano and cholesterol ester transfer protein represent novel approaches to the pharmacologic therapy of individuals with low HDL levels. The mechanisms and clinical implications of these interventions are discussed here.