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Likelihood ratio measures may be used as a standard for expressing the predictive power of noninvasive cardiovascular tests, calculated from sensitivity and specificity measures or as ratios of the predictive value odds to pretest odds for positive and negative test results. The positive likelihood ratio, (+)LR, expresses the power of a positive test result to augment an estimate of disease probability independent of the pretest prevalence of disease in a given population; the negative likelihood ratio, (-)LR, expresses the power of a negative test result to augment an estimate of the probability of no disease independent of the pretest prevalence of no disease in the same population. The likelihood ratio principle is applicable to the evaluation of the predictive power of single or combined test results reported for either dichotomous or continuous end points. This part of the perspective exemplifies application of the likelihood ratio principle in a wide variety of testing conditions for coronary artery disease followed by a discussion of the limitations of likelihood ratio computation in test power evaluation. Likelihood ratios provide a more concise and unambiguous standard for calibrating the predictive power of single and combined noninvasive cardiovascular test results than are provided by measures of sensitivity, specificity, and predictive value.

The current practice of reporting positive and negative predictive value (PV), sensitivity (Se), and specificity (Sp) as measures of the power of noninvasive cardiovascular tests has significant limitations. A test result's PV and its comparison with other test results are highly dependent on the pretest disease prevalence at which it is determined; the citation of sensitivity and specificity provides no succinct or explicit quantitation of the rule-in and rule-out power of a test. This article presents a rationale for the use of an alternative standard for expressing predictive power in the form of positive and negative likelihood ratios, (+)LR and (-)LR. The likelihood ratios are composite expressions of test power, which incorporate the Se and Sp and their respective complements [(1 - Se) and (1 - Sp)], thus yielding single unambiguous measures of positive and negative predictive power. The likelihood ratios are calculated as follows: (+)LR = Se/(1 - Sp) and (-)LR = Sp/(1 - Se). On analysis of the predictive value equations, the likelihood ratios equal the quotients of the posttest predictive value odds to the pretest prevalence odds for disease and no disease, respectively, as follows: (+)LR = (+)PVOd/POD and (-)LR = (-)PVOn/PON, where (+)PVOd is positive predictive value odds for disease, POD is prevalence odds for disease, (-)PVOn is negative predictive value odds for no disease, and PON is prevalence odds for no disease. Thus, the likelihood ratios are measures of the odds advantage in posttest probability of disease or no disease relative to pretest probability, independent of disease prevalence in the tested population. The quotients of the (+)LR or the (-)LR among test results studied in a common population are direct expressions of their relative predictive power in that population. The likelihood ratio principle is applicable to the evaluation of the predictive power of multiple tests performed in a common population and to estimating predictive power at multiple test thresholds.

Employing equilibrium-gated radionuclide ventriculography in the left anterior oblique view, six geometric models and five mathematic coefficients of nonuniformity in regional left ventricular emptying were tested for their relative mortality risk-stratifying power and capacity to augment the risk-discriminating potency of the continuous and dichotomized global ejection fraction. Radionuclide ventriculography was performed an average of 7.6 days after acute myocardial infarction. All geometric models significantly separated 20 normal subjects from 137 patients with recent infarction (p less than 0.001). Cumulative mortality data demonstrated that significant independent univariate dichotomizing potency and augmentation of the mortality risk-discriminating power of the global ejection fraction were provided by models of regional emptying that 1) conformed to coronary artery perfusion areas, 2) encompassed total ventricular counts, 3) expressed variability in regional relative to global ejection fraction, and 4) simulated a pattern of emptying directed toward the center of geometry of the left ventricle. The combination of a four quadrant geometric model with axes drawn 45 degrees above the horizontal and a coefficient of variation calculated as square root of sigma(GEF - REF)2/4 x 100/GEF (where GEF = global ejection fraction and REF = regional ejection fraction) proved to be optimal. This coefficient averaged 12.2% in normal subjects and 32.2% in patients with recent acute myocardial infarction (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Diastolic time (DT) is calculated as the cycle length (RR) minus electromechanical systole (QS2). The ratio of DT (RR-QS2) to RR interval times 100, or the percent diastole (%D), varies nonlinearly with heart rate (HR), increasing rapidly with decreasing HR. The effect of commonly used cardioactive agents on %D was studied in five groups of normal subjects. In group 1 (n = 12), propranolol (160 mg daily) increased %D from 55.9 +/- 1.7 to 64.7 +/- 1.3 (p less than 0.001) by slowing HR. In group 2 (n = 12), dobutamine (2.5 micrograms/kg/min) increased %D from 56.4 +/- 1.4 to 61.8 +/- 1.3 (p less than 0.005) by shortening the QS2. In group 3 (n = 10), Cedilanid-D (1.6 mg i.v.) increased %D from 55.5 +/- 1 to 63.2 +/- 0.7 (p less than 0.001), both by slowing the HR and shortening the QS2. In group 4 (n = 12), isoproterenol (2 micrograms/min) increased HR and shortened the QS2 significantly. The net result was a significant reduction of %D from 56.1 +/- 1.4 to 53.5 +/- 1.1, (p less than 0.05). In group 5 (n = 15), a 100-mg bolus of i.v. lidocaine did not have a significant effect on %D. This study indicates that cardiovascular drugs may have significant effects on the relative duration of diastole either by affecting HR or the duration of systole. This may have clinical implications for patients with coronary artery disease and patients with left ventricular hypertrophy, since in both cases coronary flow in mostly diastolic.

Determinations of systolic time intervals and echocardiographic measures of left ventricular performance were made in twenty-five normal subjects and 37 patients who had convalesced from a previous transmural myocardial infarction. On group analysis the patients with previous myocardial infarction demonstrated significant differences from the normals in each of the noninvasive measures. Among the noninvasive measures the PEP/LVET and deltaD% proved to be the most sensitive indicators of left ventricular dysfunction. Deviations from the normal range in PEP/LVET and deltaD% occurred in 65% to 70% of patients asymptomatic for dyspnea and fatigability (20 patients) and in 85% of patients asymptomatic for angina pectoris (13 patients). Neither the presence of phonocardiographically documented S3 or S4 or the finding of an abnormal C/T ratio on standard chest x-ray reliably detected patients with abnormal left ventricular performance. Among 26 patients studied by coronary arteriography, abnormal left ventricular performance by PEP/LVET and deltaD% occurred in less than 30% of those with obstruction (70% or greater) of one coronary artery and in over 80% of those with obstruction of two or three major arteries. A close correlation existed between the level of left ventricular performance measured by the PEP/LVET and the deltaD% (r = 0.93). These studies document the high degree of sensitivity of the noninvasive measures and demonstrate their superiority over clinical methods for detecting abnormal left ventricular performance in patients with previous myocardial infarction.

Anaerobically periused hearts from rats with experimentally induced hyperthyroidism exhibited accelerated deterioration of pacemaker activity and ventricular performance. The diminished anaerobic performance of hyperthyroid hearts was associated with decreased adenosine triphosphate (ATP) levels and a reduced rate of anaerobic glycolysis as reflected in decreased lactic acid production during 30 min of anoxic perfusion.Studies on whole heart homogenates demonstrated inhibition at the phosphofructokinase (PFK) step of the glycolytic pathway. Such inhibition was not demonstrated in the hyperthyroid heart cytosol. It is postulated that an inhibitor of PFK which resides dominantly in the particulate fraction is probably responsible for the diminished anaerobic glycolysis and performance of the hyperthyroid heart.

We have investigated the possibility that alterations in the duration of the systolic preejection period can be used to estimate adrenergic influences on the human left ventricle. The preejection period was determined from high speed, simultaneous recordings of the phonocardiogram, carotid pulse tracing, and electrocardiogram. The preejection period was shortened by isoproterenol, epinephrine, and moderate doses of norepinephrine-all of which activate beta adrenergic receptors-and by cedilanid-D. It was unaltered by changes in heart rate induced by atropine and right atrial electrical pacing. Beta adrenergic receptor blockade by propranolol abolished the shortening effects of the three catecholamines but did not inhibit that due to cedilanid-D. Vasoconstriction, both alpha adrenergic (epinephrine and norepinephrine after propranolol) and nonadrenergic (angiotensin), prolonged the preejection period. Most of the shortening of the preejection period by beta adrenergic receptor activating agents and cedilanid-D and all of the prolongation accompanying pharmacologic vasoconstriction occurred after the onset of the first heart sound, thereby excluding changes in electrical-mechanical delay as a major factor in the observed preejection period responses. Shortening of the preejection period by beta adrenergic activity induced with isoproterenol was dose-related. Increasing doses of propranolol produced parallel shifts to the right in the isoproterenol dose-response curve. In 37 normal resting subjects intravenous propranolol (10 mg) prolonged the preejection period an average of 10 (SE +/- 1) msec. In six patients with psychogenic sinus tachycardia and a patient with a pheochromocytoma the presence of excessive beta adrenergic influences on the left ventricle was demonstrated by the finding of an initially short preejection period which responded with an abnormally great prolongation to beta adrenergic receptor blockade.

Employing an isolated perfused rat heart preparation, we investigated the contribution of anaerobic metabolic energy to the performance, recoverability, and ultrastructure of the heart perfused at 32 degrees C in 5% albumin in Krebs-Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in the perfusate of the anaerobic substrate, glucose, resulted in marked improvement in electrical and mechanical performance of the heart and in enhanced recovery during the subsequent period of reoxygenation. Lactate production was fivefold greater in the glucose-supported anoxic heart than in the anoxic heart without glucose. Electron microscope sections of the hearts exposed to anoxia in the absence of glucose revealed alterations in mitochondrial morphology and dilatation of the longitudinal tubules. These morphologic changes during anoxia were averted by inclusion of glucose in the perfusion fluid. The data are consistent with the hypothesis that anaerobic energy generation plays a significant role in preserving myocardial function and structure and in promoting recoverability of the anoxic mammalian heart.