No Fever, No Murmur, No Problem? A Concealed Case of Infective Endocarditis.

BACKGROUND: Infective endocarditis is associated with significant morbidity and mortality, despite advances in diagnosis and treatment strategies. Injecting drug users are particularly at risk of endovascular infections, especially with multi-resistant and virulent microorganisms. Typically, patients with endocarditis present with constitutional symptoms, such as high fever and malaise combined with cardiorespiratory symptoms of valvular failure or emboli, such as septic pulmonary embolism. CASE REPORT: A 33-year-old female with a history of peptic ulcer disease presented to the emergency department with 3 days of increasing unilateral calf pain and swelling. There was no history of trauma or immobilization, no fever or clinical signs of sepsis or cardiopulmonary symptoms. A history of recent i.v. amphetamine injection in the forearm was elicited and empiric treatment for endovascular infection was commenced. Workup revealed methicillin-resistant Staphylococcus aureus mitral papillary endocarditis with gastrocnemius pyomyositis, multi-joint septic arthritis, and brain abscesses. After a 60-day inpatient stay, including intensive care admission for septic shock, the patient made a good recovery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The incidence of injecting drug use is increasing, and these patients are at risk of severe invasive infections with multi-resistant organisms. The emergency physician is most often responsible for the initial workup and treatment of patients with suspected infective endocarditis, with timely collection of blood cultures and appropriate antibiotics being essential interventions. This case highlights that even without fever, murmurs, or constitutional symptoms, severe multisystem infections from endocarditis can occur.

The cardiac effects of hyperbaric oxygen at 243 kPa using inchamber echocardiography.

INTRODUCTION: The adverse effects of hyperbaric oxygen (HBO) on cardiac physiology are considered a potential hazard during the treatment of some patients. The haemodynamic effects of HBO are poorly understood and the incompatibility of electrical equipment inside the chamber has made assessment difficult. At Fremantle Hyperbaric Unit, we have modified an ultrasound machine (Logiq™ e) for safe use within the hyperbaric environment. The aim of this study was to evaluate the cardiac changes that occur during HBO using in-chamber transthoracic echocardiography (TTE) in subjects without evidence of active cardiac disease. METHODS: Eleven patients and nine members of staff underwent comprehensive TTE examinations before and during HBO administered at a pressure of 243 kPa. The TTE examinations were reported by two independent cardiologists and statistically evaluated using paired Student's t-tests. RESULTS: There was a significant decrease in heart rate during HBO (65 vs. 70 bpm on air at atmospheric pressure, P = 0.002) resulting in a decrease in cardiac output (5.3 vs. 5.9 L·min⁻¹, P = 0.003). Left ventricular outflow tract (LVOT) dimension was larger during HBO than baseline imaging (2.30 vs. 2.23 cm, P = 0.0003). LVOT velocity time integrals (VTI) decreased (19.9 vs. 21.5 cm, P = 0.009) and therefore a similar stroke volume was maintained (61 vs. 65 ml, P = 0.5). Ventricular and atrial volumes, intracardiac flows and minor valvular abnormalities were not significantly affected by HBO. No adverse cardiac effects were observed. CONCLUSIONS: TTE can be safely performed within a hyperbaric chamber. Cardiac physiology is not adversely affected by HBO in individuals without active cardiac disease.

Association of the fourth heart sound with increased left ventricular end-diastolic stiffness.

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.

Accuracy of Doppler-estimated pulmonary vascular resistance in patients before liver transplantation.

The hyperdynamic circulation associated with cirrhosis is typically characterized by high cardiac output and low systemic and pulmonary vascular resistance (PVR). Approximately 4% of cirrhotic patients develop portopulmonary hypertension, which is an important predictor of hemodynamic instability after orthotopic liver transplantation. Doppler estimation of pulmonary artery systolic pressure (PASP) is used as a screening test for the presence of portopulmonary hypertension. We tested the accuracy of a noninvasive measurement of PVR (ratio of peak tricuspid regurgitant velocity [TRV] to right ventricular outflow tract velocity time integral [VTI RVOT]) to detect increased PVR in a population before liver transplantation. We compared test characteristics of the TRV/VTI RVOT ratio to echocardiographically derived PASP for detection of invasively measured PVR >1.5 Wood units. There was no significant correlation between Doppler-derived PASP and invasively measured PVR. There was a moderate and significant correlation between TRV/VTI RVOT ratio and invasively measured PVR. Compared with Doppler-derived PASP, the TRV/VTI RVOT ratio was a more accurate test for PVR >1.5 Wood units. Using a cut-off value of TRV/VTI RVOT >0.12, the sensitivity and negative predictive value for PVR >1.5 Wood units were 100%. In conclusion, the TRV/VTI RVOT ratio is a more accurate screening test for the presence of portopulmonary hypertension than PASP in patients undergoing orthotopic liver transplantation. Routine use of this ratio may decrease the need for invasive hemodynamic assessment in this patient population.

Physiology of the third heart sound: novel insights from tissue Doppler imaging.

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.

Performance of phonoelectrocardiographic left ventricular systolic time intervals and B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction.

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.

Diagnostic characteristics of combining phonocardiographic third heart sound and systolic time intervals for the prediction of 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.

Obese patients have lower B-type and atrial natriuretic peptide levels compared with nonobese.

Obesity is a risk factor for the development of heart failure, but the causal mechanism remains unclear. Impaired production or enhanced clearance of natriuretic peptides, which regulate sodium balance and sympathetic activation, may play an important role. The authors investigated the relationship of plasma B-type natriuretic peptide and atrial natriuretic peptide levels to body mass index in 100 patients referred for left heart catheterization. Hemodynamic and echocardiographic data were obtained for all study participants. Atrial natriuretic peptide and B-type natriuretic peptide levels were compared in obese (body mass index > or = 30 kg/m2) and nonobese (body mass index < 30 kg/m2) subjects. Multivariate regression analyses were performed, adjusting for clinical and hemodynamic covariates. Obese patients had significantly lower B-type natriuretic peptide (p = 0.03) and atrial natriuretic peptide (p = 0.04) levels compared with nonobese. Multivariate analysis revealed lower B-type natriuretic peptide (p = 0.095) and atrial natriuretic peptide (p = 0.007) levels in obese patients while controlling for age, sex, left ventricular end-diastolic pressure, and left ventricular ejection fraction. Low levels of circulating natriuretic peptides are thus associated with obesity and may contribute to the development of heart failure.

Relationship between accurate auscultation of a clinically useful third heart sound and level of experience.

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.

High-sensitivity C-reactive protein and parameters of left ventricular dysfunction.

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.

Association between phonocardiographic third and fourth heart sounds and objective measures of left ventricular function.

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.

Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake.

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.

Early initiation of statin therapy after a coronary event.

PURPOSE OF REVIEW: Despite improvements in the early management of acute coronary syndromes, the risk of major cardiovascular complications remains high. Lipid-modifying treatment with statins has the potential to further improve outcomes through improved endothelial function, antithrombotic and antiinflammatory actions. Statins are of proven benefit in patients with stable coronary heart disease. There has been speculation on potential mechanisms of benefit but, until recently, little data on the efficacy and safety of statins in the acute setting. Recent observational studies and randomized trials have addressed some of the questions regarding early initiation of statins in acute coronary syndromes. RECENT FINDINGS: Recent observational and randomized trials have shown that early commencement of statins in acute coronary syndromes is safe as early as 6 hours after the event and is likely to improve longer-term compliance. The current data are not sufficient to draw conclusions about the efficacy of statins early in the course of acute coronary syndromes. SUMMARY: Current management for acute coronary syndromes should include the commencement of statin therapy during initial hospital admission. This recommendation is based on safety and compliance data. More randomized trial evidence is required to determine whether early initiation will produce better outcomes than later initiation after an acute coronary event.