Plasma Oxylipins: A Potential Risk Assessment Tool in Atherosclerotic Coronary Artery Disease.

Background: While oxylipins have been linked to coronary artery disease (CAD), little is known about their diagnostic and prognostic potential. Objective: We tested whether plasma concentration of specific oxylipins may discriminate among number of diseased coronary arteries and predict median 5-year outcomes in symptomatic adults. Methods: Using a combination of high-performance liquid chromatography (HPLC) and quantitative tandem mass spectrometry, we conducted a targeted analysis of 39 oxylipins in plasma samples of 23 asymptomatic adults with low CAD risk and 74 symptomatic adults (≥70% stenosis), aged 38-87 from the Greater Portland, Oregon area. Concentrations of 22 oxylipins were above the lower limit of quantification in >98% of adults and were compared, individually and in groups based on precursors and biosynthetic pathways, in symptomatic adults to number of diseased coronary arteries [(1) n = 31; (2) n = 23; (3) n = 20], and outcomes during a median 5-year follow-up (no surgery: n = 7; coronary stent placement: n = 24; coronary artery bypass graft surgery: n = 26; death: n = 7). Results: Plasma levels of six quantified oxylipins decreased with the number of diseased arteries; a panel of five oxylipins diagnosed three diseased arteries with 100% sensitivity and 70% specificity. Concentrations of five oxylipins were lower and one oxylipin was higher with survival; a panel of two oxylipins predicted survival during follow-up with 86% sensitivity and 91% specificity. Conclusions: Quantification of plasma oxylipins may assist in CAD diagnosis and prognosis in combination with standard risk assessment tools.

Coronary autoregulation is abnormal in syndrome X: insights using myocardial contrast echocardiography.

BACKGROUND: Syndrome X in women is thought to be caused by coronary microvascular dysfunction, the exact site of which is unknown. The aim of this study was to characterize the microvascular site of dysfunction in these patients using myocardial contrast echocardiography. METHODS: Women with exertional angina, positive test results on stress imaging, but no coronary artery disease (the study group, n = 18) and age-matched control women also with no coronary artery disease (n = 17) were enrolled. Myocardial contrast echocardiography was performed at rest and during dipyridamole-induced hyperemia. Mean microbubble velocity (ß) and myocardial blood volume (A) were measured, and myocardial blood flow (A · ß) was computed. In addition, plasma concentrations of eicosanoids, female sex hormones, and C-reactive protein were measured. RESULTS: Rest ß and myocardial blood flow (A · ß) were higher in the study compared with the control women (1.61 ± 0.68 vs. 0.74 ± 0.44, P = .0001, and 157 ± 121 vs. 54 ± 54, P = 0.0001, respectively) despite similar heart rates and systolic blood pressures. After the administration of dipyridamole, whereas the changes in A and A · ß were not significantly different between the two groups, ß reserve (the ratio of stress ß to rest ß) was markedly lower in the study group (1.48 ± 0.62 vs. 2.78 ± 0.94, P = .0001). Blood hematocrit, eicosanoids, female sex hormones, glucose, and C-reactive protein were not different between the two groups. CONCLUSIONS: Coronary autoregulation is abnormal in patients with syndrome X (higher resting ß and myocardial blood flow and lower ß reserve), which suggests that the coronary resistance vessels are the site of microvascular abnormality.

A predictive instrument using contrast echocardiography in patients presenting to the emergency department with chest pain and without ST-segment elevation.

OBJECTIVE: Risk stratification of patients presenting to the emergency department (ED) with suspected cardiac chest pain (CP) and an undifferentiated electrocardiogram (ECG) is difficult. We hypothesized that in these patients a risk score incorporating clinical, ECG, and myocardial contrast echocardiography (MCE) variables would accurately predict adverse events occurring within the next 48 hours. METHODS: Patients with CP lasting for 30 minutes or more who did not have ST-segment elevation on the ECG, were enrolled. Regional function (RF) and myocardial perfusion (MP) were assessed by MCE. A risk model was developed in the initial 1166 patients (cohort 1) and validated in subsequent 720 patients (cohort 2). Any abnormality or ST changes on ECG (odds ratio [OR] 2.5; 95% confidence interval [CI], 1.4-4.5, P = .002, and OR 2.9, 95% CI, 1.7-4.8, P < .001, respectively), abnormal RF with normal MP (OR 3.5, 95% CI, 1.8-6.5, P < .001), and abnormal RF with abnormal MP (OR 9.6, 95% CI, 5.8-16.0, P < .001) were found to be significant multivariate predictors of nonfatal myocardial infarction or cardiac death. RESULTS: The estimate of the probability of concordance for the risk model was 0.82 for cohort 1 and 0.83 for cohort 2. The risk score in both cohorts stratified patients into 5 distinct risk groups with event rates ranging from 0.3% to 58%. CONCLUSION: A simple predictive instrument has been developed from clinical, ECG, and MCE findings obtained at the bedside that can accurately predict events occurring within 48 hours in patients presenting to the ED with suspected cardiac CP and an ECG that is not diagnostic for acute ischemic injury. Its application could enhance care of patients with CP in the ED. For instance, patients with a risk score of 0 could be discharged from the ED without further workup. However, this needs to be validated in a multicenter study.

Prognostic value of dipyridamole stress myocardial contrast echocardiography: comparison with single photon emission computed tomography.

BACKGROUND: Dipyridamole stress myocardial contrast echocardiography (MCE) can be used to detect coronary artery disease (CAD). Because it measures myocardial blood flow velocity in addition to measuring myocardial blood volume, it was hypothesized that it should have greater prognostic utility than single photon-emission computed tomography (SPECT), which measures only myocardial blood volume. Because blood flow mismatch precedes wall thickening (WT) abnormalities during demand ischemia, it was also postulated that perfusion on MCE would be superior to WT abnormalities on echocardiography for this purpose. METHODS: The incidence of nonfatal myocardial infarction and cardiac death was determined in 261 patients with known or suspected CAD over a mean follow-up period of 14 months who underwent simultaneous dipyridamole stress MCE and 99mTc-sestamibi SPECT. Comparisons of survival curves were conducted with stratified (and unstratified) log-rank tests. RESULTS: Abnormal results on MCE were found to be the best predictor of an adverse outcome (odds ratio, 23; 95% confidence interval, 6-201; P<.0001) and provided incremental prognostic value over clinical variables (age>60 years, the presence of >or=3 cardiac risk factors, known peripheral vascular disease, prior myocardial infarction, and left ventricular systolic function), inducible WT abnormalities, and SPECT. Prognoses were worst in patients who had both abnormal results on MCE and inducible WT abnormalities and best in those who had neither. Patients with abnormal results on MCE but no inducible WT abnormalities had intermediate outcomes. CONCLUSION: In patients with known or suspected CAD undergoing dipyridamole stress, MCE provides powerful prognostic information that is superior to clinical variables, electrocardiography, left ventricular systolic function, WT analysis, and SPECT. MCE may therefore serve as a method of choice for myocardial perfusion assessment in patients with known or suspected CAD. Larger studies are needed to confirm these findings.

Cost-efficiency of myocardial contrast echocardiography in patients presenting to the emergency department with chest pain of suspected cardiac origin and a nondiagnostic electrocardiogram.

Assessment of patients presenting to the emergency department (ED) with suspected cardiac chest pain and a nondiagnostic electrocardiogram (ECG) is lengthy and costly. It was hypothesized that myocardial contrast echocardiography (MCE) can be cost-efficient in such patients by detecting those with chest pain that is noncardiac in nature. Accordingly, cost-efficiency was evaluated in 957 patients presenting to the ED with suspected cardiac chest pain, but no ST-segment elevation on the ECG, who underwent MCE. Economic outcome calculations were based on costs estimated from national average Medicare charges adjusted by a cost-charge ratio. Based on routine clinical criteria, 641 patients (67%) were admitted to the hospital, whereas 316 (33%) were discharged directly from the ED. The average cost per patient using routine evaluation was $5,000. Patients with normal MCE results (n = 523) had a very low primary event rate (death, acute myocardial infarction) of 0.6% within 24 hours after presentation, making it relatively safe to discharge patients directly from the ED with a normal MCE result. Hence, if MCE had been used for decision making, 523 patients (55%) would have been discharged directly from the ED and 434 (45%) would have been admitted to the hospital. Preventing unnecessary admissions and tests would have saved an average of $900 per patient, in addition to reducing their ED stay. In conclusion, by excluding cardiac causes in patients presenting to the ED with chest pain and a nondiagnostic ECG, MCE can prevent unnecessary admissions and downstream resource utilization, making it a cost-efficient tool in the evaluation of these patients.

Effect of time delay on the diagnostic use of contrast echocardiography in patients presenting to the emergency department with chest pain and no S-T segment elevation.

BACKGROUND: The purpose of this study was to assess the effect of time delay on the diagnostic and prognostic use of contrast echocardiography (CE) in patients presenting to the emergency department (ED) with chest pain (CP) and no S-T segment elevation. METHODS: Patients (n = 957, 498 men) presenting to the ED within 12 hours of suggested cardiac CP underwent CE. Regional function (RF) and myocardial perfusion were interpreted separately by expert readers blinded to all other clinical data. Primary (acute myocardial infarction and total mortality) and secondary (unstable angina and revascularization) events within 24 hours of enrollment were determined. RESULTS: Patients were divided into 4 quartiles based on the time interval between their last episode of CP and CE. Patients in quartile I had CE during CP (time delay of 0 minutes). The time delay in quartiles II, III, and IV were 54 +/- 45, 213+/-54, and 556 +/- 184 minutes, respectively (P < .001). The incidence of events was similar among the 4 quartiles. In each quartile, patients with normal RF had the lowest incidence of events, whereas those with both abnormal RF and myocardial perfusion had the highest incidence of events. Patients with abnormal RF but normal myocardial perfusion had an intermediate event rate. CONCLUSIONS: In patients presenting to the ED within 12 hours of CP, the timing of CE does not influence its ability to predict events that occur 24 hours later. These findings have important implications in the performance of CE in the ED.

Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure.

OBJECTIVES: We studied structural and functional cardiac alterations in obstructive sleep apnea (OSA), their relationship to the severity of OSA, and the effects of treatment with continuous positive airway pressure (CPAP). BACKGROUND: Obstructive sleep apnea may influence the cardiac function by several mechanisms in the awake patient. METHODS: Left and right ventricular morphology and function were studied using echocardiography before and after treatment with CPAP in symptomatic patients (Epworth sleepiness score, 10 +/- 4.8) with severe OSA (apnea-hypopnea index [AHI], 42 +/- 24). The patients (n = 43, 32 men) had no known cardiac disease and were obese (body mass index, 31.6 +/- 5.4 kg/m2). The same echocardiographic parameters were studied in age-matched overweight patients (n = 40; body mass index, 26.4 +/- 2.3 kg/m2). RESULTS: The patients were hypertensive (systolic blood pressure, 153 +/- 25 mm Hg), with a higher resting heart rate (77 +/- 10 beats/min, p = 0.008) compared with age-matched control patients (n = 40). There was right ventricular dilatation, hypertrophic interventricular septum, reduced left ventricular stroke volume, tissue Doppler-determined systolic and diastolic velocities of the left and right ventricle, and normal pulmonary artery pressure. The structural and functional parameters were significantly associated with AHI (p < 0.004). Multiple stepwise regression showed the interventricular septum thickness, right ventricular free wall, and mitral annulus tissue Doppler systolic velocities to be predictive of a higher AHI (p < 0.001). Six months after treatment with CPAP, significant improvements were observed in the symptoms and hemodynamics, as well as left and right ventricular morphology and function. CONCLUSIONS: The structural and functional consequences of OSA on the heart are influenced by the severity of AHI. These effects are reversible if the apneic episodes are abolished.

Myocardial contrast echocardiography versus Thrombolysis In Myocardial Infarction score in patients presenting to the emergency department with chest pain and a nondiagnostic electrocardiogram.

OBJECTIVES: We hypothesized that regional function (RF) and myocardial perfusion (MP) are superior to the Thrombolysis In Myocardial Infarction (TIMI) score for diagnosis and prognostication in patients presenting to the emergency department (ED) with chest pain (CP) and a nondiagnostic electrocardiogram. BACKGROUND: Rapid diagnosis and prognostication is difficult in patients presenting to the ED with suspected cardiac CP. METHODS: Contrast echocardiography was performed to assess RF and MP on 957 patients presenting to the ED with suspected cardiac CP and a nondiagnostic electrocardiogram. A modified TIMI (mTIMI) score was calculated from six immediately available variables. A full TIMI score also was derived after troponin levels were able to be accessed adequately. Follow-up was performed for early (within 24 h), intermediate (30 day), and late primary (death and myocardial infarction) or secondary (unstable angina and revascularization) events. RESULTS: The mTIMI score was unable to discriminate between intermediate- compared to high-risk patients at any follow-up time point, whereas only 2 of 523 patients with normal RF had an early primary event. Regional function provided incremental prognostic value over mTIMI scores for predicting intermediate and late events. In patients with abnormal RF, MP further classified patients into intermediate- and high-risk groups. The full TIMI score could not improve upon these results at any follow-up time point. CONCLUSIONS: Contrast echocardiography can rapidly and accurately provide short-, intermediate-, and long-term prognostic information in patients presenting to the ED with suspected cardiac CP even before serum cardiac markers are known. Integrating contrast echocardiography into the ED evaluation of CP may improve the risk stratification of such patients.

Regional left ventricular perfusion and function in patients presenting to the emergency department with chest pain and no ST-segment elevation.

AIMS: We hypothesized that the assessment of left ventricular regional function (RF) and myocardial perfusion (MP) will provide incremental value over routine evaluation in patients who present to the emergency department (ED) with chest pain (CP) and no ST-segment elevation. METHODS AND RESULTS: In addition to routine clinical evaluation, patients with suspected cardiac CP and no ST-segment elevation were evaluated in the ED for RF and MP using contrast echocardiography (CE). Cardiac-related death, acute myocardial infarction, unstable angina pectoris, congestive heart failure (CHF), and revascularization were considered as events within 48 h (early). Of the 1017 patients studied, 166 (16.3%) had early events. Adding RF increased the prognostic information of clinical and EKG variables significantly (Bonferroni corrected P<0.0001) for predicting these events. When MP was added, significant additional prognostic information was obtained (Bonferroni corrected P=0.0002). All patients were followed for a median of 7.7 months (25th-75th percentiles: 2.7-12.5) Of these, 292 (28.7%) had events. Adding RF increased the prognostic information of clinical and EKG variables for determining the risk of events significantly (Bonferroni corrected P<0.0001), which was further increased by adding MP (Bonferroni corrected P<0.0001). CONCLUSION: Early assessment of RF on CE adds significant diagnostic and prognostic value to routine evaluation in patients presenting to the ED with suspected cardiac CP and no ST-segment elevation. MP provides additional significant value. CE could be a valuable tool in the early triage and management of CP patients presenting to the ED.

Measurement of myocardial blood flow velocity reserve with myocardial contrast echocardiography in patients with suspected coronary artery disease: comparison with quantitative gated Technetium 99m sestamibi single photon emission computed tomography.

BACKGROUND: The ability of high and low mechanical index (MI) imaging methods during myocardial contrast echocardiography (MCE) to assess the physiologic significance of coronary stenoses were compared with technetium 99m sestamibi single photon emission computed tomography (SPECT) in patients. METHODS: Intermittent ultraharmonic imaging (high MI) and power modulation angio (low MI) were performed during continuous infusions of the echo-enhancing contrast agent, Optison, at rest and after dipyridamole stress in 39 patients. Technetium 99m sestamibi SPECT was performed simultaneously. Images from the 3 apical windows were divided into 6 walls. Myocardial blood flow (MBF) velocity and MBF velocity reserve were quantified from pulsing interval versus acoustic intensity MCE curves in each wall using postprocessed images. RESULTS: Approximately 25% of the myocardial walls could not be analyzed from MCE because of artifacts. MBF velocity and MBF derived from both MCE methods increased significantly after dipyridamole in healthy patients (n = 143 and 129 walls for high and low MI, respectively), compared with those with either reversible (n = 11 and 10 walls for high and low MI, respectively) or fixed defects (n = 18 and 14 walls for high and low MI, respectively) on SPECT. Consequently, MBF velocity and MBF reserve were significantly greater for patients with normal perfusion. Receiver operator characteristic curves obtained for MBF velocity reserve provided a sensitivity and specificity of 82% and 87%, respectively, for high MI; versus 64% and 96%, respectively, for low MI imaging after uninterpretable images were excluded from analysis. CONCLUSIONS: Both high and low MI MCE imaging techniques can be used to determine the presence of perfusion defects as identified by technetium 99m sestamibi SPECT. Low MI imaging methods have a number of drawbacks that limit its sensitivity compared with high MI techniques.

Natural history of moderate mitral valve stenosis.

BACKGROUND: With the introduction of surgery and percutaneous balloon valvuloplasty for relieving severe mitral stenosis the natural history of the disease has markedly altered. OBJECTIVES: To determine the natural history of the disease in patients with moderate mitral valve stenosis. METHODS: Demographic, clinical and echocardiographic data were evaluated in 36 patients with moderate mitral stenosis during a follow-up of 71 +/- 15 months. RESULTS: The 36 patients comprised 32 women and 4 men with a mean age of 43.7 +/- 12.2 years; 28 were Jewish and 8 were of Arab origin. During follow-up, there was a significant decrease in mitral valve area, with an increase in mean mitral valve gradient and score. Mean loss of mitral valve area was 0.04 +/- 0.11 cm 2/year. No correlation was found between disease progression and age, past mitral valve commissurotomy, baseline mean gradient or mitral valve score. Larger baseline mitral valve area (P = 0.007) and Arab origin (P = 0.03) had an independent correlation to loss of mitral valve area. Fifteen patients (42%) did not demonstrate any loss in mitral valve area during the follow-up period. CONCLUSIONS: The rate of mitral valve narrowing in patients with moderate mitral stenosis is variable and cannot be predicted by patient's age, past commissurotomy, valve score or gradient. Secondly, larger baseline mitral valve area and Arab origin showed an independent correlation to loss of mitral valve area; and finally, in many patients valve area did not change over a long observation period.

Assessment of the vascularity of a left ventricular mass using myocardial contrast echocardiography.

In addition to a thrombus, an intracardiac mass lesion can represent a primary cardiac tumor, or a metastatic lesion to the heart. The echocardiographic appearance and location of the mass, as well as the associated clinical scenario provide useful clues regarding cause, but these echocardiographic features alone may not always be diagnostic. Because most benign cardiac tumors are relatively avascular, the vascularity of a mass may be a feature that can help differentiate benign from malignant tumors. We present a case of a patient with a history of malignant melanoma who was found incidentally to have a cardiac mass on echocardiography. Contrast echocardiography (CE) was used to evaluate the vascularity of the mass. This case is compared with another patient with an apical thrombus, which represents an "avascular" intracardiac structure.

Multivariate Analysis of Left Ventricular Mass Determinants in Adults: Different Patterns in Men and Women.

Echocardiographic left ventricular mass (LVM) estimates are strong predictors of subsequent mortality and cardiovascular events. It is known that blood pressure (BP), weight (WT), and age are significantly correlated with LVM. We hypothesized that stroke volume (SV) measured by Doppler echocardiography would also be correlated with LVM. Two hundred and thirteen patients referred for routine echocardiography had determination of LVM, cuff BP, and Doppler SV. Those with localized LV disease, valvular disease, or cor pulmonale were excluded. In both men and women, systolic BP (SBP) was more closely correlated with LVM than was diastolic blood pressure or mean arterial pressure, and SV was more closely correlated with LVM than cardiac output or cardiac index. Stepwise regression, followed by multiple regression showed that four variables (WT, SV, SBP, and AGE) explained 32.3% of the variability in LVM in men and 48.5% of the variability in LVM in women. WT and SV were significant determinants of LVM in both men and women. Age was also significant in men and SBP was also significant in women. For both men and women, SV was more significantly correlated with LVM than was SBP. The changes in LVM associated with 1 SD increments of SV and SBP, respectively, were 8 and 5 g for men and 13 and 11 g for women. We conclude that men and women have different patterns of variables influencing LVM. Doppler echocardiographic SV is a newly described determinant of LVM that has a greater correlation with LVM than does SBP. This study reemphasizes the importance of WT as the major determinant of LVM. (ECHOCARDIOGRAPHY, Volume 13, January 1996)