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Biomedical subjects

Elyse Foster

Publications and source records attributed to Elyse Foster.

At least 37 records · Page 2Linked to original sources

Closed-chest cell injections into mouse myocardium guided by high-resolution echocardiography.

The mouse is an important model for the development of therapeutic stem cell/bone marrow cell implantation to treat ischemic myocardium. However, its small heart size hampers accurate implantation into the left ventricular (LV) wall. Precise injections have required surgical visualization of the heart, which is subject to complications and is impractical for delayed or repeated injections. Furthermore, the thickness of the myocardium is comparable to the length of a needle bevel, so surgical exposure does not prevent inadvertent injection into the LV cavity. We describe the use of high-resolution echocardiography to guide nonsurgical injections accurately into the mouse myocardial wall. We optimized this system by using a mixture of ultrasound contrast and fluorescent microspheres injected into the myocardium, which enabled us to interpret the ultrasound image of the needle during injection. Quantitative dye injection studies demonstrated that guided closed-chest injections and open-chest injections deliver comparable amounts of injectate to the myocardium. We successfully used this system in a mouse myocardial infarction model to target the injection of labeled cells to a region adjacent to the infarct. Intentional injection of tracer into the LV cavity resulted in a small accumulation in the myocardium, suggesting that non-guided cell injections into mouse hearts may appear to be successful even if the majority of the injectate is lost in the chamber. The use of this system will allow more precise cellular implantation into the mouse myocardium by accurately guiding injections to desired locations, confirming successful implantation of cells, in a clinically relevant time frame.

Animals↗

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.

Adult↗

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.

Adult↗

A comparison of cardiac resynchronization by sequential biventricular pacing and left ventricular pacing to simultaneous biventricular pacing: rationale and design of the DECREASE-HF clinical trial.

BACKGROUND: The first generation of cardiac resynchronization therapy (CRT) devices approved for the treatment of heart failure used simultaneous biventricular (BiV) pacing to achieve ventricular resynchronization. Left ventricular pacing alone and sequential BiV pacing also show promise as alternative ways to deliver CRT, but have not been studied together in a large randomized trial. METHODS: The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE-HF) Trial is a randomized, double-blind, 3-arm study of patients in New York Heart Association Class III or IV with an ejection fraction of 35% or less and a QRS duration > or =150 ms. Patients are randomized to receive either left ventricular pacing, simultaneous BiV pacing, or sequential BiV pacing. CONCLUSION: The study uses a novel composite endpoint that combines peak oxygen consumption and left ventricular end systolic dimension, thus combining a measure of symptomatic improvement (peak oxygen consumption) with a physiologic measure of ventricular reverse remodeling (left ventricular end systolic dimension) into a single composite score. Additionally, the safety and effectiveness of the CONTAK RENEWAL 2/4/4HE/EASYTRAK 2 system will be evaluated using: heart failure-related adverse events; system-related complications; left ventricular lead-related complications; detection time of induced ventricular fibrillation; and left ventricular lead performance (pacing threshold, pacing impedance, and R-wave amplitude).

Cardiac Output↗

Age and aneurysm position predict patterns of left ventricular dysfunction after subarachnoid hemorrhage.

Cardiac injury, including left ventricular dysfunction, frequently occurs in patients with subarachnoid hemorrhage. Patterns of left ventricular dysfunction often do not follow coronary artery distributions, and may correlate with myocardial sympathetic innervation. Left ventricular dysfunction of the anterior and anteroseptal walls that spares the apex is unusual for patients with myocardial infarction and may represent a neurally mediated pattern of injury. We performed serial echocardiography on 225 patients with subarachnoid hemorrhage and classified those with regional wall-motion abnormalities as following either an apex-sparing (AS) or apex-affected (AA) pattern. Wall-motion abnormalities were found in 61 of 225 patients studied (27%). The AS pattern was found in 49% of these patients. Younger age and anterior aneurysm position were independent predictors of this AS pattern. Both patterns of wall-motion abnormalities appear to be transient, reversible phenomena. The AS pattern may represent a unique form of neurally mediated cardiac injury.

Adult↗

Correlation between right ventricular indices and clinical improvement in epoprostenol treated pulmonary hypertension patients.

The aim of this study was to evaluate which parameter of right ventricular (RV) echocardiographic best mirrors the clinical status of patients with pulmonary arterial hypertension. Patients with pulmonary arterial hypertension on epoprostenol therapy were identified via hospital registry. Twenty patients, (16 females, 4 males) were included in the study, 9 with primary pulmonary hypertension and 11 with other diseases. Echocardiograms before therapy and at 22.7 (+/-9.3) months into therapy were compared. The right ventricular myocardial performance index (RVMPI) was measured as the sum of the isometric contraction time and the isometric relaxation time divided by right ventricular ejection time. Other measures included peak tricuspid regurgitation jet velocity (TRV), pulmonary artery systolic pressure (PASP), pulmonary valve velocity time integral (PVVTI), PASP/PVVTI (as an index of total pulmonary resistance) and symptoms by New York Heart Association (NYHA) functional class. Echo parameters of right ventricular function were analyzed in patients, before and during therapy. There was significant improvement of NYHA class in patients following epoprostenol therapy (P < 0.0001). Peak tricuspid regurgitant jet velocity (pre 4.2 +/- 0.6 m/sec, post 3.8 +/- 0.7 m/sec, P = 0.02) and PASP/PVVTI (pre 6.7 +/- 3.3 mmHg/m per second, post 4.8 +/- 2.2 mmHg/m per second, P < 0.0001) were significantly improved during treatment. RVMPI did not improve (pre 0.6 +/- 0.3, post 0.6 +/- 0.3, P = 0.54). Changes in NYHA class did not correlate with changes in RVMPI (P = 0.33) or changes in PASP/PVVTI (P = 0.58). Despite significant improvements in TRV, PASP/PVVTI, and NYHA class, there was no significant change in RVMPI on epoprostenol therapy. Changes in right ventricular indices were not correlated with changes in NYHA class.

Antihypertensive Agents↗

Prevalence and implications of diastolic dysfunction after subarachnoid hemorrhage.

INTRODUCTION: Electrocardiographic changes, troponin release, and reduced left ventricular ejection fraction have been described after subarachnoid hemorrhage (SAH). Little is known about the occurrence of diastolic dysfunction in this setting. The purpose of this study was to determine the prevalence of diastolic dysfunction and its association with cardiac outcomes after SAH. METHODS: SAH patients were prospectively enrolled into the study, and echocardiographic, clinical, chest X-ray, and cardiac troponin I data were obtained on days 1, 3, and 6 after enrollment. Each echocardiogram included Doppler recordings of mitral inflow and pulmonary venous flow. For each study, diastolic function was categorized as normal, impaired relaxation, pseudonormal, or restrictive. The relationships between diastolic dysfunction and pulmonary edema-elevated cardiac troponin I and left ventricular contractile dysfunction were quantified using both univariate and multivariate statistical methods. Clinical predictors of diastolic dysfunction were defined by multivariate logistic regression. RESULTS: Of 223 enrolled subjects, 207 had technically adequate Doppler data. Diastolic dysfunction was observed in 71% of subjects. The prevalence of diastolic versus systolic dysfunction in 44 patients with pulmonary edema was 91 versus 37%, respectively (p=0.001). After multivariate statistical adjustment, diastolic dysfunction remained a significant predictor of pulmonary edema (odds ratio [OR] 3.34, 95% CI=1.05-10.59). Diastolic dysfunction also was associated with troponin release (p=0.02). A history of hypertension and increasing age were predictive of diastolic dysfunction. CONCLUSION: Diastolic dysfunction is common after SAH. It is associated with history of hypertension and older age and may explain the development of pulmonary edema in many SAH patients.

Adult↗

Beating heart catheter-based edge-to-edge mitral valve procedure in a porcine model: efficacy and healing response.

BACKGROUND: Surgical edge-to-edge repair has been used in the treatment of mitral regurgitation. We evaluated the ability of a catheter-delivered clip (Evalve, Inc) to achieve edge-to-edge mitral valve approximation without cardiopulmonary bypass and the healing response of this technique. METHODS AND RESULTS: Twenty-one pigs underwent general anesthesia and left thoracotomy. A 10F flexible delivery catheter with a clip was placed into the left atrium. With echocardiographic and fluoroscopic guidance, the clip grasped and approximated the mid portion of the anterior and posterior leaflets. After a double orifice had been confirmed, the clip was detached and the catheter withdrawn. All animals survived and had successful clip placement. Three animals were euthanized at 4 weeks, 9 at 12 weeks, 1 at 17 weeks, 7 at 24 weeks, and 1 at 52 weeks. The clip was well positioned, with leaflet approximation in all animals except 1, in which the clip separated from the posterior leaflet at 4 weeks without affecting valve function. The clip was modified and implanted in 4 pigs; all were intact at 12 to 24 weeks. Scanning electron microscopy showed clip encapsulation with complete endothelialization. Mitral stenosis and thromboembolism did not develop. Two animals developed endocarditis (1 at 12 weeks and 1 at 17 weeks). Progressive healing occurred in all other animals. CONCLUSIONS: Edge-to-edge mitral valve approximation can be successfully and reliably achieved with a catheter-delivered clip without cardiopulmonary bypass, resulting in durable healing. The success of this device supports the development of a percutaneous catheter-based system for mitral valve repair.

Animals↗

Is PA-PWRmax truly a preload-independent index of myocardial contractility in anesthetized humans?

This study tested the hypothesis that the preload-adjusted maximal power index (PA-PWRmax) is a load-independent index of human myocardial contractility. Based on the ventricular pressure-volume relationship and derived from stroke work, the index is the product of instantaneous ventricular pressure and volume changes, divided by a correction term of end-diastolic volume (EDV2) or end-diastolic area (EDA3/2) to adjust for preload effects. Echocardiographic measures of instantaneous ventricular area change may be used to obtain PA-PWRmax noninvasively. We prospectively evaluated 28 human subjects undergoing cardiac evacuation before cardiopulmonary bypass procedures. Continuous peripheral arterial pressure, pulmonary arterial pressure, and echocardiographic views of the left ventricle in the transgastric short-axis view were recorded. Simultaneously gated instantaneous fractional shortening (FS) and PA-PWRmax indices were calculated, with FS = (EDA - ESA)/EDA and PA-PWRmax = [MAP (EDA - ESA)]/ EDA3/2, where ESA = end-systolic area and MAP = instantaneous mean arterial pressure. FS decreased uniformly with cardiac evacuation and decreasing pulmonary artery diastolic pressure (t = -5.4; 95% confidence interval, -10 to -0.046; p < 0.001), as did PA-PWRmax (t = -5.8; 95% confidence interval, -2.25 to -1.08; p < 0.001). FS and PA-PWRmax showed a strong downward correlation (r = 0.81). Unlike previous studies of autonomically denervated animals, our study did not find PA-PWRmax to be preload independent, perhaps because of the instantaneous homeostatic mechanisms of the human autonomic nervous system linking contractility to loading conditions.

Anesthesia, General↗

Impact of tricuspid regurgitation on long-term survival.

OBJECTIVES: The goal of this study was to examine mortality associated with tricuspid regurgitation (TR) after controlling for left ventricular ejection fraction (LVEF), right ventricular (RV) dilation and dysfunction, and pulmonary artery systolic pressure (PASP). BACKGROUND: Tricuspid regurgitation is a frequent echocardiographic finding; however, the association with prognosis is unclear. METHODS: We retrospectively identified 5,223 patients (age 66.5 +/- 12.8 years; predominantly male) undergoing echocardiography at one of three Veterans Affairs Medical Center laboratories over a period of four years. Follow-up data were available for four years (mean 498 +/- 402 days). Kaplan-Meier and proportional hazards methods were used to compare differences in survival among TR grades. RESULTS: Mortality increased with increasing severity of TR. The one-year survival was 91.7% with no TR, 90.3% with mild TR, 78.9% with moderate TR, and 63.9% with severe TR. Moderate or greater TR was associated with increased mortality regardless of PASP (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.16 to 1.49 for PASP >40 mm Hg; HR 1.32, 95% CI 1.05 to 1.62 for PASP < or =40 mm Hg) and LVEF (HR 1.49, 95% CI 1.34 to 1.66 for EF <50%; HR 1.54, 95% CI 1.37 to 1.71 for EF > or =50%). When adjusted for age, LVEF, inferior vena cava size, and RV size and function, survival was worse for patients with moderate (HR 1.17, 95% CI 0.96 to 1.42) and severe TR (HR 1.31, 95% CI 1.05 to 1.66) than for those with no TR. CONCLUSIONS: We conclude that increasing TR severity is associated with worse survival in men regardless of LVEF or pulmonary artery pressure. Severe TR is associated with a poor prognosis, independent of age, biventricular systolic function, RV size, and dilation of the inferior vena cava.

Aged↗

Predictors of neurocardiogenic injury after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) frequently results in myocardial necrosis with release of cardiac enzymes. Historically, this necrosis has been attributed to coronary artery disease, coronary vasospasm, or oxygen supply-demand mismatch. Experimental evidence, however, indicates that excessive release of norepinephrine from the myocardial sympathetic nerves is the most likely cause. We hypothesized that myocardial necrosis after SAH is a neurally mediated process that is dependent on the severity of neurological injury. METHODS: Consecutive patients admitted with SAH were enrolled prospectively. Predictor variables reflecting demographic (age, sex, body surface area), hemodynamic (heart rate, systolic blood pressure), treatment (phenylephrine dose), and neurological (Hunt-Hess score) factors were recorded. Serial cardiac troponin I measurements and echocardiography were performed on days 1, 3, and 6 after enrollment. Troponin level was treated as a dichotomous outcome variable. We performed univariate and multivariate analyses on the relationships between the predictor variables and troponin level. RESULTS: The study included 223 patients with an average age of 54 years. Twenty percent of the subjects had troponin I levels >1.0 microg/L (range, 0.3 to 50 microg/L). By multivariate logistic regression, a Hunt-Hess score >2, female sex, larger body surface area and left ventricular mass, lower systolic blood pressure, and higher heart rate and phenylephrine dose were independent predictors of troponin elevation. CONCLUSIONS: The degree of neurological injury as measured by the Hunt-Hess grade is a strong, independent predictor of myocardial necrosis after SAH. This finding supports the hypothesis that cardiac injury after SAH is a neurally mediated process.

Adult↗

Demonstration of coronary artery flow using transthoracic Doppler echocardiography.

Transthoracic Doppler echocardiography is emerging as a promising method for evaluating coronary artery disease. After a period of training, detection and measurement of distal left anterior descending coronary artery flow with transthoracic Doppler echocardiography is feasible in more than 90% of the patients. Using transthoracic Doppler echocardiography with a high-frequency transducer and special setting of low Nyquist limits, pathologic coronary flow dynamics can be demonstrated. Measurement of coronary flow reserve may impact diagnosis or clinical treatment in those: (1) with anginal chest pain and angiographically normal coronary arteries; (2) with intermediate-grade coronary obstruction where the physiologic significance is in doubt; and (3) who have had an attempt at revascularization and the effectiveness of the therapy is uncertain.

Blood Flow Velocity↗

Effects of resynchronization therapy on cardiac function in pacemaker patients "upgraded" to biventricular devices.

INTRODUCTION: Cardiac resynchronization therapy (CRT) improves echocardiographic measures of cardiac function and has a variable effect on QRS duration in patients with left bundle branch block (LBBB). How CRT affects these indices in patients with right ventricular (RV) pacing-induced LBBB who are "upgraded" with left ventricular (LV) leads for CRT is unknown. We studied the echocardiographic effects of RV pacing and CRT in patients with prior continuous RV pacing after LV lead placement. METHODS AND RESULTS: Fifteen consecutive patients (age 73 +/- 11 years, LV ejection fraction 24 +/- 6%, QRS duration 190 +/- 27 msec) with New York Heart Association class IIIB-IV symptoms and continuous RV pacing underwent LV lead placement for CRT. Echocardiography and ECG were performed sequentially during RV pacing and CRT. CRT was associated with significantly reduced QRS duration (190 +/- 27 msec vs 165 +/- 18 msec, P = 0.005) and reduced LV electromechanical delay (180 +/- 33 msec vs 161+/- 43 msec). Baseline QRS duration correlated with CRT response. After CRT, patients had significant improvements in indices of systolic function, including LV ejection fraction, myocardial performance index (MPI), and LV ejection time. Abnormal baseline MPI was associated with greater improvement after CRT. LV end-diastolic and systolic volumes were similarly decreased with CRT. Mitral valve deceleration time, an index of diastolic function, was not affected by CRT. CONCLUSION: "Upgrading" RV paced patients with advanced heart failure to CRT improves measures of electrical and LV mechanical synchrony and improves systolic function.

Aged↗

Harmonic imaging improves sensitivity at the expense of specificity in the detection of patent foramen ovale.

UNLABELLED: Contrast echocardiography using agitated saline is widely employed to detect right to left shunt in patients with suspected patent foramen ovale (PFO). The sensitivity of fundamental transthoracic echocardiography (FTTE) is often limited by poor far-field resolution. The purpose of this study was to evaluate the test characteristics of harmonic imaging during transthoracic echocardiography (HTTE) for the detection of PFO. METHODS: Sixty-four patients referred for transesophageal echo (TEE) for clinical indications underwent FTTE and HTTE during saline contrast injections. RESULTS: TEE identified nine PFOs. For FTTE, the sensitivity was 78% and the specificity was 100%. For HTTE, the sensitivity was 100% and the specificity was 82%. All ten false positives with HTTE occurred after five cardiac cycles, suggesting transpulmonary transit of the bubbles. CONCLUSION: In the detection of PFO, HTTE improves sensitivity at the expense of specificity, particularly if the timing of contrast appearance in the left heart is ignored.

Adult↗