Implementation of echocardiography core laboratory best practices: a case study of the PARTNER I trial.

BACKGROUND: Multicenter clinical trials use echocardiographic core laboratories to ensure expertise and consistency in the assessment of imaging eligibility criteria, as well as safety and efficacy end points. The aim of this study was to report the real-world implementation of guidelines for best practices in echocardiographic core laboratories, including their feasibility and quality results, in a large, international multicenter trial. METHODS: Processes and procedures were developed to optimize the acquisition and analysis of echocardiograms for the Placement of Aortic Transcatheter Valves (PARTNER) I trial of percutaneous aortic valve replacement for aortic stenosis. Comparison of baseline findings in the operative and nonoperative cohorts and reproducibility analyses were performed. RESULTS: Echocardiography was performed in 1,055 patients (mean age, 83 years; 54% men) The average peak and mean aortic valve gradients were 73 ± 24 and 43 ± 15 mm Hg, and the average aortic valve area was 0.64 ± 0.20 cm(2). The average ejection fraction was 52 ± 13% by visual estimation and 53 ± 14% by biplane planimetry. The mean left ventricular mass index was 151 ± 42 g/m(2). The inoperable cohort had lower left ventricular mass and mass indexes and tended to have more severe mitral regurgitation. Core lab reproducibility was excellent, with intraclass correlation coefficients ranging from 0.92 to 0.99 and κ statistics from 0.58 to 0.85 for key variables. The image acquisition quality improvement process brought measurability to >85%, which was maintained for the duration of the study. CONCLUSIONS: This real-world echocardiographic core lab experience in the PARTNER I trial demonstrates that a high standard of measurability and reproducibility can result from extensive quality assurance efforts in both image acquisition and analysis. These results and the echocardiographic data reported here provide a reference for future studies of aortic stenosis patients and should encourage the wider use of echocardiography in clinical research.

Prognosis after change in left ventricular ejection fraction during mental stress testing in patients with stable coronary artery disease.

Previous studies of patients with stable coronary artery disease have demonstrated that decreases in the left ventricular ejection fraction (LVEF) during acute mental stress are predictive of adverse clinical outcomes. The aim of the present study was to examine the prospective relation of mental stress on clinical outcomes in a sample of 138 patients with stable coronary artery disease. Patients underwent mental stress testing and were followed for a median of 5.9 years to assess the occurrence of the combined end point of myocardial infarction or all-cause mortality. There were 32 events (17 nonfatal myocardial infarctions and 15 deaths) over the follow-up period. Of the 26 patients who exhibited myocardial ischemia during mental stress testing, 11 (42%) sustained subsequent clinical events, compared to 21 of the 112 patients (19%) who showed no mental stress-induced ischemia. LVEF change during mental stress was also related to the clinical events in a graded, continuous fashion, with each 4% decrease from the LVEF at rest associated with an adjusted hazard ratio of 1.7, (95% confidence interval 1.1 to 2.6, p = 0.011). In conclusion, reductions in the LVEF during mental stress are prospectively associated with adverse clinical outcomes.

Independent prognostic value of echocardiography and N-terminal pro-B-type natriuretic peptide in patients with heart failure.

BACKGROUND: Echocardiographic indices of cardiac structure and function and natriuretic peptide levels are strong predictors of mortality in patients with heart failure. Whether cardiac ultrasound and natriuretic peptides provide independent prognostic information is uncertain. METHODS: Echocardiograms and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) were prospectively performed in 211 patients with left ventricular systolic dysfunction who were followed for a median of 4 years. Echocardiographic variables and NT-proBNP were examined as predictors of all-cause mortality in univariable and multivariable proportional hazards models. RESULTS: Participants averaged 57 years old (SD 12 years) and had a mean left ventricular ejection fraction of 32% (SD 11%). A total of 71 patients (34%) died during the follow-up period. N-terminal pro-brain natriuretic peptide was a strong predictor of mortality (P < .001) as were multiple echocardiographic measures. In models that included age and NT-proBNP, with other clinical variables eligible for entry by stepwise selection, significant predictors of death included left ventricular ejection fraction (P = .013) and end-diastolic volume (P < .001), left atrial volume index (P = .005), right atrial volume index (P = .003), and tricuspid regurgitation area (P = .015). In models that also included left ventricular ejection fraction, end-diastolic volume of the left ventricle (P = .019), left atrial volume (P = .026), and right atrial volume (P = .020) remained significant predictors of mortality. CONCLUSIONS: Left ventricular size and function and left atrial and right atrial sizes are significant predictors of all-cause mortality in patients with heart failure, independent of NT-proBNP levels and other clinical variables.

Relationship of depression to death or hospitalization in patients with heart failure.

BACKGROUND: Depression is widely recognized as a risk factor in patients with coronary heart disease. However, patients with heart failure (HF) have been less frequently studied, and the effect of depression on prognosis, independent of disease severity, is uncertain. METHODS: Two hundred four outpatients having a diagnosis of HF, with a ventricular ejection fraction of 40% or less, underwent baseline assessments including evaluation of depressive symptoms using the Beck Depression Inventory and of HF severity determined by plasma N-terminal pro-B-type natriuretic peptide. Cox proportional hazards regression analyses were used to examine the effects of depressive symptoms on a combined primary end point of death and hospitalizations because of cardiovascular disease (hereafter referred to as cardiovascular hospitalization) during a median follow-up of 3 years. RESULTS: Symptoms of depression (Beck Depression Inventory score) were associated with risk of death or cardiovascular hospitalization (P<.001) after controlling for established risk factors including HF disease severity, ejection fraction, HF etiology, age, and medications. Clinically significant symptoms of depression (Beck Depression Inventory score >/=10) were associated with a hazard ratio of 1.56 (95% confidence interval, 1.07-2.29) for the combined end point of death or cardiovascular hospitalization. Contrary to our expectation, antidepressant medication use was associated with increased likelihood of death or cardiovascular hospitalization (hazard ratio, 1.75; 95% confidence interval,1.14-2.68, P =.01) after controlling for severity of depressive symptoms and for established risk factors. CONCLUSIONS: Symptoms of depression were associated with an adverse prognosis in patients with HF after controlling for HF severity. The unexpected association of antidepressant medications with worse clinical outcome suggests that patients with HF requiring an antidepressant medication may need to be monitored more closely.

Impaired endothelial function in coronary heart disease patients with depressive symptomatology.

OBJECTIVES: The purpose of this study was to assess whether depressive symptomatology was associated with vascular endothelial dysfunction in patients with coronary heart disease (CHD). BACKGROUND: In patients with CHD, the presence of depression is associated with a two to four times increased risk of mortality, but the disease pathways involved are uncertain. Endothelial dysfunction is an established risk factor for cardiovascular events in patients with CHD. METHODS: Flow-mediated dilation (FMD) of the brachial artery, a measure of endothelial function, was assessed in 143 patients (99 men, 44 women), ages 40 to 84 years (mean age, 63 +/- 10 years), with documented CHD. RESULTS: Patients with significant depressive symptomatology, as indicated by a Beck Depression Inventory (BDI) score > or = 10 (n = 47) showed attenuated FMD (p = 0.001) compared with patients that were not depressed (BDI < 10; n = 96). The use of antidepressant medication was associated with improved FMD (p < 0.05). CONCLUSIONS: The increased risk of cardiovascular events in CHD patients with elevated symptoms of depression may be mediated, in part, by endothelial dysfunction.

Depression and increased myocardial ischemic activity in patients with ischemic heart disease.

BACKGROUND: Depression is relatively common in patients with ischemic heart disease (IHD) and is associated with increased risk of mortality and morbidity. However, the mechanisms by which depression adversely affects clinical outcomes of patients with IHD are unknown. This study examined the relationship between depression and myocardial ischemia during mental stress testing and during daily living in patients with stable IHD.Methods and results The Center for Epidemiological Studies-Depression scale (CES-D) was administered to 135 patients with IHD to evaluate depressive symptoms. Radionuclide ventriculography was used to evaluate the occurrence of left ventricular wall motion abnormality (WMA) during mental stress and exercise testing. Forty-eight-hour ambulatory electrocardiography was used to assess myocardial ischemia during daily living. The mean CES-D score was 8.2 (SD 7.4, range 0-47) with a median of 7. Logistic regression models using restricted cubic splines revealed a curvilinear relation among CES-D scores and the probability of ischemia. For patients with CES-D scores 19, the relation among scores and ischemia during mental stress tended to be inversely related, but the portion of the sample is very small. Similar patterns of results were noted for CES-D scores and ischemia during daily life. CONCLUSIONS: Patients with mild to moderate depressive symptoms (CES-D scores

Relationship of clinic, ambulatory, and laboratory stress blood pressure to left ventricular mass in overweight men and women with high blood pressure.

OBJECTIVE: This study was designed to evaluate the relationship between left ventricular (LV) mass and blood pressure (BP) recorded in the following contexts: in the clinic, using standard auscultatory procedures, during a typical day using ambulatory BP monitoring, and in the laboratory environment during behavioral stress testing. METHODS: Ninety-seven men and women with clinic systolic blood pressure (SBP) of 130 to 180 mm Hg and/or diastolic blood pressure (DBP) of 85 to 110 mm Hg and mild to moderate obesity were included in the study. Laboratory stressors included the following tasks: Public Speaking; Anger Interview; Mirror Trace; and Cold Pressor. LV mass was measured using echocardiography and adjusted for body size by dividing by height(2.7) to yield LV mass index (LVMI). RESULTS: LVMI was positively correlated with clinic SBP (r = 0.24, p <.05), ambulatory SBP (r = 0.34, p <.01), and aggregated laboratory stress SBP (r = 0.28, p <.01). Of the individual stressors, only SBP responses to the Mirror Trace and Cold Pressor tasks were independently correlated with LVMI (r = 0.35 and 0.34, respectively, p values <.01). Hierarchical regression analyses revealed that laboratory stress SBP remained a significant predictor of LVMI, after controlling for BMI and clinic pressure. CONCLUSIONS: These findings suggest that cardiovascular responses to behavioral stress are associated with individual differences in LVMI in men and women with high blood pressure who are overweight. Laboratory studies of behavioral stress may help promote our understanding of the pathophysiology of LVH.