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The signs and symptoms of systolic heart failure are frequently insensitive and nonspecific, making an accurate bedside diagnosis of left ventricular systolic dysfunction (LVSD) challenging. B-type natriuretic peptide (BNP) is often used, but is not diagnostically useful when in the indeterminate range. The authors investigated the diagnostic test characteristics of acoustic cardiographic parameters to identify patients with LVSD. Four hundred thirty-three patients with contemporaneous measurements of computerized acoustic cardiography, BNP, and echocardiography were included. The acoustic cardiographic model outperformed BNP alone at detecting reduced left ventricular ejection fraction (C statistic, 0.88 vs 0.67; P<.0001). The acoustic model with BNP did not perform better than the acoustic model alone (P=.14). Within the indeterminate BNP range, the acoustic model outperformed BNP (C statistic, 0.89 vs 0.64; P<.0001). Noninvasive computerized acoustic cardiography predicted LVSD in a diverse population. This acoustic cardiographic model outperformed BNP alone for predicting LVSD., (© 2010 Wiley Periodicals, Inc.)

Background: The authors previously described an acoustic cardiographic model that predicted echocardiographic correlates of elevated left ventricular (LV) filling pressure. This study evaluated this bedside acoustic cardiographic model against invasive measurements of LV filling pressure., Methods and Results: Data were prospectively obtained from 68 adults referred for right heart catheterisation. Acoustic cardiographic measurements were obtained during right heart catheterisation. Elevated LV filling pressure was defined as a pulmonary capillary wedge pressure (PCWP) > or =15 mm Hg. Parameters generated from a previous dataset used for the current analysis were measures of LV systolic time, maximum negative area of the P wave, QTc interval and third heart sound (S3) score. Logistic regression was used to calculate area under the curve (AUC). Of the 66 patients included, 39 had elevated PCWP. Estimating the probability of an elevated PCWP from the derived model resulted in an AUC of 0.72 (95% CI 0.60 to 0.85). When the regression model's parameters were held constant but the parameter estimates were allowed to vary, the AUC in the validated model was 0.76 (95% CI 0.64 to 0.88). At a specificity of 90% the positive likelihood ratio (LR+) was 5.0 (1.7 to 15.3) and the negative likelihood ratio was 0.49 (0.34 to 0.71)., Conclusion: These data demonstrate that the four-variable model predicts elevated filling pressure at the bedside with high specificity and an intermediate LR+. With improvements in sensitivity and further prospective validation of this model in a cohort of emergency department patients with undifferentiated dyspnoea this may be a useful bedside diagnostic modality.

Background: Although the standard 12-lead electrocardiogram (ECG) is considered the gold standard to diagnose acute myocardial ischemia, nearly half of ECGs are nondiagnostic in patients who present with chest pain and have subsequent confirmation of infarction with positive serum biomarkers., Methods: A prospective study was performed to investigate the frequency and intensity of diastolic third and fourth heart sounds (S3 and S4), as measured by computerized acoustic cardiography, with myocardial ischemia induced by balloon occlusion during percutaneous coronary intervention., Results: In our 24 subjects, during percutaneous coronary intervention-induced ischemia, a new or increased intensity S3 or S4 developed in 67%. Ten (67%) of 15 patients without clinical ST criteria for ischemia also developed new or increased-intensity diastolic heart sounds., Conclusions: The combined use of diastolic heart sounds, as a measurement of ventricular dysfunction, with the standard ECG may improve the noninvasive diagnosis of myocardial ischemia that is likely to develop into infarction.

Aims: Ventricular interactions may be mediated by loading conditions and biventricular timing and coordination. We sought to understand the relationships between right (RV) and left ventricular (LV) function and dyssynchrony, examine the RV correlates of LV dyssynchrony, and determine whether improved loading conditions affect inter-ventricular interaction., Methods and Results: In 25 heart failure patients [15 with left ventricular ejection fraction (LVEF) < 40%; 10 with LVEF >/= 50%], Doppler echocardiography and invasive bi-ventricular pressure-volume haemodynamics were obtained at baseline and 30 min after infusion of the recombinant B-type natriuretic peptide vasodilator nesiritide. RV and LV intra-ventricular dyssynchrony was measured invasively using a pressure-conductance catheter. Patients with reduced LVEF had greater LV dyssynchrony (31 +/- 3 vs. 24 +/- 7%; P = 0.003) compared to those with preserved LVEF. Tricuspid annular plane systolic excursion (TAPSE) had the highest correlation with LV dyssynchrony (r = -0.52; P = 0.0002) compared to other RV echocardiographic parameters. The association between TAPSE and LV dyssynchrony was independent of RVEF and LVEF (P = 0.008). There were no acute changes in the correlations between LV dyssynchrony and TAPSE after nesiritide., Conclusion: TAPSE and LV dyssynchrony are strongly associated, independent of RV and LV ejection fraction. Of the RV echocardiographic parameters, TAPSE has the highest predictive value of LV dyssynchrony, and remained significant after vasodilator unloading.

Background: To evaluate the usefulness of currently accepted echocardiographic parameters of diastolic function to assess the acute change in left ventricular end-diastolic pressure (LVEDP) following the administration of nesiritide in a heart failure population., Methods: In 25 heart failure patients (15 with systolic dysfunction, 10 with preserved ejection fraction [EF]), Doppler echocardiography, right and left heart catheterization, and invasive biventricular pressure hemodynamics were obtained at baseline and 30 minutes after nesiritide infusion., Results: Twenty-four patients had sufficient echocardiographic images for analysis. The mean age was 60 +/- 11 years, 48% were male, 56% had coronary artery disease, and 64% had hypertension. Right ventricular systolic pressure (RVSP) had the highest correlation with LV filling pressure: pulmonary capillary wedge pressure (PCWP), pre-A wave LV, and LVEDP (r = 0.66, P = 0.0009; r = 0.63, P = 0.002; r = 0.72, P = 0.0002, respectively). Following nesiritide administration, the mean PCWP decreased from 17.1 +/- 7.8 mmHg at baseline to 9.6 +/- 6.2 mmHg (P < 0.001). Change in RVSP had the highest correlation with change in PCWP (r =-0.67, P = 0.10) and change in LVEDP (r =-0.71, P = 0.07)., Conclusion: Echocardiographic parameters are frequently assessed in attempts to estimate left heart diastolic pressures. In heart failure patients, RVSP appears to be the best predictor of LVEDP, outperforming tissue Doppler E/E'. RVSP was found to be the best echocardiographic predictor of change in LV filling pressure with intravenous vasodilator therapy in heart failure patients. RVSP may provide a noninvasive means of assessing response to cardiac therapy.

Background: Although the fourth heart sound (S4) is thought to be associated with a stiff left ventricle, this association has never been proven. Recently, single-beat estimation of the end-diastolic pressure volume relationship (EDPVR) has been characterized (P = alphaV(beta)), allowing the estimation of EDPVR in larger groups of patients. We hypothesized that the S(4) is associated with an upward- and leftward-shifted EDPVR, indicative of elevated end-diastolic stiffness., Methods and Results: Ninety study participants underwent acoustic cardiographic analysis, echocardiography, and left heart catheterization. We calculated alpha and beta coefficients to define the nonlinear slope of the EDPVR using the single-beat method for measuring left ventricular end-diastolic elastance. In the P = alphaV(beta) EDPVR estimation, alpha was similar (P = .31), but beta was significantly higher in the S(4) group (5.96 versus 6.51, P = .002), signifying a steeper, upward- and leftward-shifted EDPVR curve in subjects with an S(4). The intensity of the S(4) was associated with both beta (r = 0.42, P < .0001) and E/E' / stroke volume index, another index of diastolic stiffness (r = 0.39, P = .0008). On multivariable analysis, beta remained associated with the presence (P = .008) and intensity (P < .0001) of S(4) after controlling for age, sex, and ejection fraction., Conclusions: The S(4) is most likely generated from an abnormally stiff left ventricle, supporting the concept that the S(4) is a pathologic finding in older patients.

Background: The third heart sound (S(3)) is thought to be caused by the abrupt deceleration of left ventricular (LV) inflow during early diastole, increased LV filling pressures, and decreased LV compliance. We sought to determine whether the ratio of early mitral inflow velocity to diastolic velocity of the mitral annulus (E/E') could confirm the proposed mechanism of the S(3)., Methods: A total of 90 subjects underwent phonocardiography, echocardiography, tissue Doppler imaging, and left-sided heart catheterization., Results: Phonocardiography detected an S(3) in 21 patients (23%). Subjects with an S(3) had lower ejection fraction (P = .0006) and increased E deceleration rate (P < .0001), E/E' (P < .0001) and filling pressures (P < .0001). The phonocardiographic S(3) confidence score correlated with E/E' (r = 0.46; P < .0001) and E deceleration rate (r = 0.43, P = .0001). Of the echocardiographic variables, only E/E' was independently associated with the S(3) confidence score (P = .009), independently of invasively determined LV filling pressures (P = .001)., Conclusions: The most important determinants of the pathologic S(3) are an increased deceleration rate of early mitral inflow, elevated LV filling pressures, and abnormal compliance of the myocardium as measured by tissue Doppler imaging.

Background: Systolic time intervals measured by echocardiography and carotid artery tracings are validated methods of assessing left ventricular function. However, the clinical utility of phonoelectrocardiographic systolic time intervals for predicting heart failure using newer technology has not been evaluated., Methods: We enrolled 100 adult patients undergoing left heart catheterization. Participants underwent computerized phonoelectrocardiographic analysis, left ventricular end-diastolic pressure (LVEDP) measurement, transthoracic echocardiographic measurement of left ventricular ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. The heart rate-adjusted systolic time intervals included the time from the Q wave onset to peak S1 (electromechanical activation time, EMAT), Q wave onset to peak S2 (electromechanical systole, Q-S2), and peak S1 to peak S2 (left ventricular systolic time, LVST). Left ventricular dysfunction was defined as the presence of both LVEDP >15 mmHg and LVEF <50%., Results: EMAT (r =-0.51; P < 0.0001), EMAT/LVST (r =-0.41; P = 0.0001), and Q-S2 (r =-0.39; P = 0.0003) correlated with LVEF, but not with LVEDP. An abnormal EMAT > or =15 (odds ratio 1.38, P < 0.0001) and EMAT/LVST > or =0.40 (OR 1.13, P = 0.002) were associated with left ventricular dysfunction. EMAT > or =15 had 44% sensitivity, 94% specificity, and a 7.0 likelihood ratio for left ventricular dysfunction, while EMAT/LVST > or =0.40 had 55% sensitivity, 95% specificity, and a 11.7 likelihood ratio. In patients with an intermediate BNP (100-500 pg/mL), the likelihood ratio increased from 1.1 using the BNP result alone to 11.0 when adding a positive EMAT test for predicting left ventricular dysfunction., Conclusions: Phonoelectrocardiographic measures of systolic time intervals are insensitive but highly specific tests for detecting abnormalities in objective markers of left ventricular function. EMAT and EMAT/LVST provide diagnostic information independent of BNP for detecting patients with left ventricular dysfunction.

Background: The third heart sound (S3) and systolic time intervals (STIs) are validated clinical indicators of left ventricular (LV) dysfunction. We investigated the test characteristics of a combined score summarizing S3 and STI results for predicting LV dysfunction., Methods and Results: A total of 81 adults underwent computerized phonelectrocardiography for S3 and STI (Audicor, Inovise Medical Inc), cardiac catheterization for LV end-diastolic pressure (LVEDP), echocardiography for LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. LV dysfunction was defined as both an LVEDP >15 mm Hg and LVEF <50%. The STI measured was the electromechanical activation time (EMAT) divided by LV systolic time (LVST). Z-scores for the S3 confidence score and EMAT/LVST were summed to generate the LV dysfunction index. The LV dysfunction index had a correlation coefficient of 0.38 for LVEDP (P = .0003), -0.53 for LVEF (P < .0001), and 0.35 for BNP (P = .0008). This index had a receiver operative curve c-statistic of 0.89 for diagnosis of LV dysfunction; a cutoff >1.87 yielded 72% sensitivity, 92% specificity, 9.0 positive likelihood ratio, and 88% accuracy., Conclusions: In this preliminary study, the LV dysfunction index combined S3 and STI data from noninvasive electrophonocardiography, and yielded superior test characteristics compared to the individual tests for the diagnosis of LV dysfunction.

Background: Poor performance by physicians-in-training and interobserver variability between physicians have diminished clinicians' confidence in the value of the third heart sound (S3)., Methods: To determine whether auscultation of a clinically useful S3 improves with advancing levels of experience, we performed a prospective, blinded, observational study of 100 patients undergoing left-sided heart catheterization. Patients underwent blinded auscultation by 4 physicians (each from 1 of 4 different levels of experience), phonocardiography, measurement of blood B-type natriuretic peptide levels, echocardiography for measurement of left ventricular ejection fraction, and cardiac catheterization for measurement of left ventricular end-diastolic pressure., Results: Whereas residents' and interns' auscultatory findings demonstrated no significant agreement with phonocardiographic findings, an S3 auscultated by cardiology fellows (kappa = 0.37; P<.001) and cardiology attendings (kappa = 0.29; P = .003) agreed with phonocardiographic findings. Although the sensitivities of the S3 were low (13%-52%) for identifying patients with abnormal measures of left ventricular function, the specificities were high (85%-95%), with the best test characteristics exhibited by phonocardiography and more experienced physicians. The S3 detected by attendings and fellows was superior in distinguishing an elevated B-type natriuretic peptide level, a depressed left ventricular ejection fraction, or an elevated left ventricular end-diastolic pressure (P = .002-.02 for attendings and .02-.03 for fellows) compared with residents (P = .02-.47) or interns (P = .09-.64)., Conclusions: The S3 auscultated by more experienced physicians demonstrated fair agreement with phonocardiographic findings. Although correlations were superior for phonocardiography, the associations between the S3 and abnormal markers of left ventricular function improved with each level of auscultator experience.

Background: Elevated levels of high-sensitivity C-reactive protein (CRP), an inflammatory marker, have been associated with heart failure. However, it is not known which parameters of left ventricular dysfunction correlate with elevated levels of CRP., Methods and Results: In this cross-sectional study of 98 patients referred for cardiac catheterization, we investigated whether commonly used clinical indices of left ventricular dysfunction correlated with CRP levels. CRP levels were elevated to a greater degree in participants with diabetes mellitus (P =.006) and heart failure (P =.003). Increased CRP levels were associated with increased plasma levels of B-type natriuretic peptide (BNP; P =.0001), decreased left ventricular ejection fraction (LVEF; P =.02), and increased left-ventricular end-diastolic pressure (LVEDP; P =.0005). After multivariable adjustment, LVEDP and CRP were independently associated (P =.046)., Conclusion: CRP is increased in patients with heart failure. Of the clinical parameters of left ventricular dysfunction, direct measurement of left ventricular end-diastolic pressure is most closely associated with CRP.

Context: The third (S3) and fourth (S4) heart sounds detected by phonocardiography are considered to represent the criterion standards of the gallop sounds, but their test characteristics have not been explored., Objective: To determine the diagnostic test characteristics of the S3 and S4 for prediction of left ventricular dysfunction using a computerized heart sound detection algorithm., Design, Setting, and Participants: Prospective study of 90 adult patients undergoing elective left-sided heart catheterization at a single US teaching hospital between August 2003 and June 2004. The mean age was 62 (SD, 13) years (range, 24-90 years) and 61 (68%) were male. Within a 4-hour period, participants underwent computerized heart sound phonocardiographic analysis, cardiac catheterization, transthoracic echocardiography, and blood sampling for assessment of an S3/S4, left ventricular end-diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), and B-type natriuretic peptide (BNP), respectively., Main Outcome Measures: Diagnostic test characteristics of the computerized phonocardiographic S3 and S4 using markers of left ventricular function as criterion standards., Results: Mean (SD) LVEDP was significantly elevated (18.4 [6.9] mm Hg vs 12.1 [7.3] mm Hg; P<.001), mean (SD) LVEF was reduced (49.4% [20.2%] vs 63.6% [14.8%]; P<.001), and median (interquartile range) BNP was elevated (330 [98-1155] pg/mL vs 86 [41-192] pg/mL; P<.001) in those with an S3, S4, or both compared with patients without a diastolic heart sound. The sensitivities of these heart sounds to detect an elevated LVEDP, reduced LVEF, or elevated BNP were 41%, 52%, and 32% for an S3, and 46%, 43%, and 40% for an S4, respectively. For abnormal levels of the same markers of ventricular function, the specificities of the S3 were 92%, 87%, and 92%, while the specificities of the S4 were 80%, 72%, and 78%, respectively., Conclusions: Neither the phonocardiographic S3 nor the S4 is a sensitive marker of left ventricular dysfunction. The phonocardiographic S3 is specific for left ventricular dysfunction and appears to be superior to the moderate specificity of the phonocardiographic S4.

Background: Levosimendan is a calcium-sensitizing agent and an inodilator under current investigation in the treatment of decompensated heart failure. The effects of intravenous levosimendan on the human coronary vasculature, together with myocardial wall stress and oxygen uptake, have not been adequately studied., Methods and Results: Ten adult patients underwent right- and left-heart catheterization. Baseline coronary blood flow was determined with quantitative coronary angiography and an intracoronary Doppler-tipped guidewire. Myocardial oxygen uptake was measured with a coronary sinus catheter. Echocardiography was performed before and 30 minutes after an intravenous infusion of levosimendan (24-microg/kg bolus over 10 minutes) was begun. Pulmonary capillary wedge decreased 37% (P=0.009), cardiac output increased 9% (P=0.04), and systemic vascular resistance decreased 18% (P<0.001). Left ventricular ejection fraction increased 20% (P=0.009), and meridional systolic wall stress decreased 48% (P=0.009). Coronary artery diameter increased 10% at 15 minutes (P=0.001) and 11% at 30 minutes (P=0.01). Coronary artery velocity increased 10% over baseline (P=0.04). Coronary blood flow increased 45% (P=0.02), whereas coronary resistance decreased 36% at 30 minutes (P=0.03). Myocardial oxygen extraction decreased 9% at 30 minutes (P=0.04)., Conclusions: Levosimendan given intravenously exerts vasodilator effects on human coronary conductance and resistance arteries. Despite a decrease in coronary perfusion pressure, coronary blood flow is increased. A reduction in coronary vascular resistance and a decrease in coronary venous oxygen content indicate primary coronary vasodilation by levosimendan. Improved left ventricular systolic function and decreased myocardial oxygen extraction suggest improved myocardial efficiency.