BACKGROUND Although structural heart disease is often present in patients with nonrheumatic atrial fibrillation, the echocardiographic precursors of atrial fibrillation have not been reported previously. In this elderly, population-based cohort, our objective was to examine prospectively the echocardiographic predictors of nonrheumatic atrial fibrillation. METHODS AND RESULTS Subjects in the Framingham Heart Study were routinely evaluated with M-mode echocardiography; 1924 subjects, ranging in age from 59 to 90 years, comprised the population at risk. Cox proportional hazards modeling was used to analyze the association of selected echocardiographic features with atrial fibrillation risk after adjustment for age, sex, hypertension, coronary heart disease, congestive heart failure, diabetes, and valvular heart disease. During a mean follow-up interval of 7.2 years, 154 subjects (8.0%) developed atrial fibrillation. Multivariable stepwise analysis identified left atrial size (hazard ratio [HR] per 5-mm increment, 1.39; 95% confidence interval [CI], 1.14 to 1.68), left ventricular fractional shortening (HR per 5% decrement, 1.34; 95% CI, 1.08 to 1.66), and sum of septal and left ventricular posterior wall thickness (HR per 4-mm increment, 1.28; 95% CI, 1.03 to 1.60) as independent echocardiographic predictors of atrial fibrillation. For each of the echocardiographic predictors, risk increased progressively over successive quartiles. Moreover, risk increased markedly when highest-risk-quartile measurements for these features were present in combination; the cumulative 8-year age-adjusted atrial fibrillation rates were 7.3% and 17.0%, respectively, when one and two or more highest-risk-quartile features were present, compared with 3.7% when none was present. CONCLUSIONS In this elderly, population-based sample, left atrial enlargement, increased left ventricular wall thickness, and reduced left ventricular fractional shortening were predictive of risk for nonrheumatic atrial fibrillation. These echocardiographic precursors offer prognostic information beyond that provided by traditional clinical atrial fibrillation risk factors.

Echocardiographic predictors of nonrheumatic atrial fibrillation. The Framingham Heart Study.

Assessment of left ventricular systolic and diastolic pump properties is fundamental to advancing the understanding of cardiovascular pathophysiology and therapeutics, especially for heart failure. The use of end-systolic and end-diastolic pressure-volume relationships derived from measurements of instantaneous left ventricular pressure-volume loops emerged in the 1970s as a comprehensive approach for this purpose. As invasive and noninvasive techniques for measuring ventricular volume improved over the past decades, these relations have become commonly used by basic, translational, and clinical researchers. This review summarizes 1) the basic concepts underlying pressure-volume analysis of ventricular and myocardial systolic and diastolic properties, 2) deviations from ideal conditions typically encountered in real-life applications, 3) how these relationships are appropriately analyzed, including statistical analyses, and 4) the most common problems encountered by investigators and the appropriate remedies. The goal is to provide practical information and simple guidelines for accurate application and interpretation of pressure-volume data as they pertain to characterization of ventricular and myocardial properties in health and disease.

Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers.

the method and initial application Noninvasive determination of left ventricular end-systolic stress: validation of ISSN: 1524-4539 Copyright © 1982 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 1982, 65:99-108 Circulation http://circ.ahajournals.org/content/65/1/99.citation located on the World Wide Web at: The online version of this article, along with updated information and services, is

Noninvasive determination of left ventricular end-systolic stress: validation of the method and initial application.

BASIC RESEARCH on the ventricular pressure-volume loop diagram has been revived.' Several investigators2-8 proposed that the relationship of end-systolic pressure (or wall stress) to end-systolic volume (or some dimension) may be useful in evaluating the contractile state of the heart. Grossman et al. published an important clinical study\" in 1977; many others followed. At the 1980 annual meetings of the American Heart Association and American College of Cardiology, at least 11 papers0-21 were presented concerning the end-systolic relationship between pressure and volume, pressure and thickness, and wall stress and normalized volume. Several significant studies2' 39 have also appeared in the past 5 years; a dozen clinical studies have been published. With this popularity, the original meanings of end-systolic pressure-volume relation and its parameters (e.g., Emax, m, V0 and Vd) have become ambiguous. Sometimes they were purposely modified to attempt to improve their value and other times just to make the measurement easy. Whatever the reasons, it seems appropriate to review these modifications with reference to the proponents' original ideas about fundamental aspects.

The end-systolic pressure-volume relation of the ventricle: definition, modifications and clinical use.

We developed methods for identifying beta-adrenergic receptors in human right ventricular endomyocardial biopsy tissue with the radioligand (-)[125I]iodocyanopindolol (ICYP). Specific ICYP binding in a crude, high-yield membrane preparation derived from endomyocardial biopsy tissue was high (specificity greater than 90%), of high affinity (KD around 20 pM), saturable and stereospecific for the (-) vs the (+) isomer of isoproterenol. Subjects with mild-moderate and severe biventricular dysfunction had respective decreases in beta-adrenergic receptor density of 38.2% and 57.7% when normalization methods were averaged, with no significant differences in ICYP dissociation constant. A subgroup of subjects was subdivided by left ventricular ejection fraction (LVEF) into those with mild cardiac dysfunction (LVEF less than 0.50 greater than 0.40) and severe heart failure (LVEF less than 0.20) and given graded sequential infusions of dobutamine and calcium gluconate. Those with severe cardiac dysfunction had marked impairment of the dobutamine dP/dt and stroke work index response, whereas these responses to calcium did not differ in the two groups. These data indicate that in the intact human heart endomyocardial biopsy may be used for direct analysis of beta-adrenergic receptors, heart failure-associated myocardial beta-adrenergic down-regulation begins with mild-moderate ventricular dysfunction, reduction in myocardial beta-receptor density is related to degree of heart failure, and beta-receptor down-regulation is associated with pharmacologically specific impairment of the beta-agonist-mediated contractile response.

Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response.

A thesis recently developed from a series of experiments on the isolated canine left ventricle is described. It is claimed that the ventricular presure/volume ratio at end-systole is relatively insensitive to cardiac loading and varies greatly in response to changes in ventricular contractility. The clinical viability of this basic finding rests on the substitution of diameter for volume in this formulation. Diameter can be measured using a noninvasive ultrasonic technique in the clinic. Accordingly, end-systolic pressure/diameter ratio was studied in the isolated preparation and found to be similarly insensitive to loading conditions and sensitive to inotropic interventions. A further analysis of the pressure/diameter ratio in the ventricle of the conscious dog is in progress. In parallel with these studies, use of the pressure/diameter ratio to evaluate contractility in cardiac patients is being tested. The preliminary findings from conscious dogs and clinic patients are briefly discussed.

Kenneth M. Bakalar

Papers

End-systolic pressure/volume ratio: A new index of ventricular contractility☆