Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study.

PURPOSE: We sought to determine the importance of a third heart sound (S(3)) and its relation to hemodynamic and valvular dysfunction. SUBJECTS AND METHODS: We prospectively enrolled 580 patients who had isolated valvular regurgitation (mitral, n = 299; aortic, n = 121) or primary left ventricular dysfunction with or without functional mitral regurgitation (n = 160). We analyzed the associations between the clinical finding of an audible S(3) (as noted in routine clinical practice by internal medicine physicians) and hemodynamic alterations measured by comprehensive quantitative Doppler echocardiography. RESULTS: S(3) was more prevalent in patients with primary left ventricular dysfunction (46%, n = 73) than in organic mitral (16%, n = 47) or aortic (12%, n = 14) regurgitation (P <0.001). Patients with an S(3) were more likely to have class III-IV symptoms (55% [74 of 137] vs. 18% [80 of 443] of those without an S(3), P <0.001) and had a higher mean [+/- SD] pulmonary pressure (55 +/- 15 vs. 41 +/- 11 mm Hg, P <0.001). An S(3) was also related to a higher early filling velocity due to a greater filling volume, restrictive filling, or both. An S(3) was a marker of severe regurgitation (regurgitant fraction > or =40%) in patients with primary left ventricular dysfunction (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.1 to 5.5), mitral regurgitation (OR = 17; 95% CI: 5.8 to 52), and aortic regurgitation (OR = 7.1; 95% CI: 1.8-28). An S(3) was also associated with restrictive filling in primary left ventricular dysfunction (OR = 3.0; 95% CI, 1.6 to 5.9), marked dilatation in mitral regurgitation (OR = 20; 95% CI: 6.8 to 58), and an ejection fraction (<50%) in aortic regurgitation (OR = 19; 95% CI: 6.0 to 62). CONCLUSION: An audible S(3) is an important clinical finding, indicating severe hemodynamic alterations, and should lead to a comprehensive assessment and consideration of vigorous medical or surgical treatment.

A perspective on standardizing the predictive power of noninvasive cardiovascular tests by likelihood ratio computation: 1. Mathematical principles.

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.

A perspective on standardizing the predictive power of noninvasive cardiovascular tests by likelihood ratio computation: 2. Clinical applications.

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.

Hypertrophic cardiomyopathy with obstruction: important diagnostic clue provided by the direction of the mitral regurgitation jet.

We present an unusual case of hypertrophic cardiomyopathy complicated by mitral regurgitation resulting from chordal rupture with flail posterior mitral leaflet. The diagnosis was suggested by the presence of an anteriorly directed mitral regurgitation jet on transthoracic color flow imaging, in addition to the typical posterolateral-lateral jet caused by systolic anterior mitral motion. The flail posterior leaflet was confirmed by transesophageal echocardiography, and the patient underwent mitral valve repair in addition to myectomy. This combination of hypertrophic cardiomyopathy and flail mitral leaflet usually requires surgical intervention, and prompt diagnosis is important. The presence of an anteriorly directed mitral regurgitant jet should always raise suspicion of posterior mitral leaflet abnormality.

Quantitative measures of regional asynergy add independent prognostic information to left ventricular ejection fraction in patients with prior myocardial infarction.

The purpose of this study was to determine if quantitative measurements of regional asynergy add independent prognostic information to global ejection fraction in patients with chronic coronary artery disease. Four hundred eighty-six patients with a history of Q-wave myocardial infarction who underwent gated-equilibrium radionuclide angiography at least 3 months after infarction were monitored for a median duration of 4.7 years. During follow-up there were 95 deaths. Four of five regional asynergy indexes analyzed were associated with overall mortality. The strength of the association between overall mortality and the index that proved to be optimal (univariate chi2 = 26.4, p < 0.001) was stronger than for global ejection fraction (univariate chi2 = 21.5, p < 0.001). For patients with global ejection fraction <40%, 4-year survival was 87% for those with a low asynergy index versus 65% for those with a high asynergy index (p = 0.016). In conclusion, indexes of regional asynergy add independent prognostic information to global left ventricular ejection fraction.

Augmentation of mortality risk discriminating power of left ventricular ejection fraction by measures of nonuniformity in systolic emptying on radionuclide ventriculography.

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)

Left ventricular mass and systolic performance in chronic systemic hypertension.

This study was undertaken to define the relation between the extent of left ventricular (LV) hypertrophy and ventricular systolic performance in patients with chronic systemic hypertension. Ninety patients with chronic systemic hypertension were compared with 41 normal subjects as determined by angiography. LV mass was estimated from the M-mode echocardiogram. Patients were separated into 3 groups: those with LV mass of less than 2 (group I, n = 58), 2 to 4 (group II, n = 21) and more than 4 (group III, n = 11) standard deviations above mean normal. The ratio of preejection period to LV ejection time (PEP/LVET), percent shortening of the echocardiographic internal diameter (% delta D) and velocity of circumferential shortening (Vcf) were used as indexes of LV systolic performance. The frequency of abnormality, expressed as percent of patients in groups I, II and III, was 33%, 55% and 85% for PEP/LVET, 15%, 35% and 72% for % delta D, and 0%, 15% and 55% for Vcf. For each group PEP/LVET was the most frequently abnormal measure and Vcf was the least frequent abnormality. Calculation of peak and end-systolic wall stress was used as an index of the adequacy of LV hypertrophy. This index was significantly reduced in group I, did not differ from control in group II and was significantly increased in group III, indicating that hypertrophy was appropriate to wall tension in groups I and II. It is concluded that the occurrence of LV dysfunction with increasing LV mass in patients with moderate LV hypertrophy (group I and II) reflects a deficiency in intrinsic contractile performance of the hypertrophied myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

The therapeutic implications of diastolic time changes in systemic hypertension.

Twenty-five patients with chronic systemic hypertension were studied. Systolic time intervals and diastolic time were determined at baseline and after 12 weeks of therapy with nadolol, with or without bendroflumethiazide (treatment phase I), then after 12 weeks of therapy with hydralazine, bendroflumethiazide, or both (treatment phase II). Systolic, diastolic, and mean blood pressures were equally controlled after either treatment regimen. Heart rate was significantly slower after treatment phase I compared to baseline or after treatment phase II (p less than 0.001). Systolic time per minute was significantly shorter and diastolic time per beat and per minute were significantly longer after treatment phase I compared to baseline or after treatment phase II (p less than 0.001). Double and triple products decreased after either mode of therapy; however, these parameters were significantly lower after treatment phase I compared to treatment phase II (p less than 0.01). These changes in systolic and diastolic time and double and triple products may be of clinical significance during therapy of chronic systemic hypertension and may help explain the regression of left ventricular hypertrophy in patients with hypertension treated with sympathetic blocking agents.

Identification of patients with improved survival following coronary bypass surgery.

This study was designed to determine whether left ventricular performance measured noninvasively from the systolic time intervals could identify patients in whom coronary bypass surgery may improve survival. 71 patients with two- or three-vessel disease undergoing coronary bypass surgery were compared with 78 matched medically treated patients. All patients had recuperated from myocardial infarction by a mean of 17.6 months when systolic time intervals were performed. Surgical and medical patients were classified preoperatively into those with normal and those with abnormal left ventricular performance by preejection period/left ventricular ejection time (PEP/LVET less than or equal to 0.42 and greater than 0.42, respectively). Survival was analyzed by life table and log-rank test. Cumulative 5-year survival in patients with normal left ventricular performance was not statistically different in surgical and medical groups (96 vs. 93%, respectively). In contrast, cumulative survival in patients with abnormal left ventricular performance was significantly greater in the surgical group when compared to the medical group (84 vs. 62, p less than 0.01). Among the patients with abnormal left ventricular function, the mean PEP/LVET and the average vessel disease were not different in the medical and surgical groups. Multivariate analysis of 17 other clinical and laboratory risk variables were not different between these two groups. It is concluded that coronary bypass surgery my improve survival in patients with two- or three-vessel disease and left ventricular dysfunction.

Assessment of ventricular function by combined noninvasive measures: factors accounting for methodologic disparities.

We studied the predictive accuracy and disparities among cineventriculographic ejection fraction, pre-ejection period over left ventricular ejection time (PEP/LVET) obtained from the systolic time intervals and the percent shortening of the internal echocardiographic diameter (% delta D) in assessing left ventricular performance in 453 consecutive patients without valvular heart disease. In 308 patients all three tests were normal, and in 78 patients all three tests were abnormal. Overall agreement (predictive accuracy) among ejection fraction (normal greater than or equal to 57), % delta D (normal greater than or equal to 28%) and PEP/LVET (normal less than or equal to 0.42) was 85%. In 67 patients disparities among the tests as measures of global left ventricular performance were found. The major mechanisms accounting for such disparities were: (a) large segmental contraction abnormalities which selectively distort the % delta D and ejection fraction and (b) diminished isovolumic pressure (less than 45 mmHg) which distorts PEP/LVET. When patients with segmental contraction abnormalities and low isovolumic pressure were excluded the agreement between PEP/LVET and ejection fraction was 97%, ejection fraction and % delta D 98% and PEP/LVET and % delta D 97%. The combined uses of systolic time intervals and echocardiogram minimizes error due to segmental contraction abnormalities and isovolumic pressure. If both PEP/LVET and % delta D are concordant the agreement with ejection fraction is 94% for normal and 99% for abnormal left ventricular function.