Mid wall fibrosis on CMR with late gadolinium enhancement may predict prognosis for LVAD and transplantation risk in patients with newly diagnosed dilated cardiomyopathy-preliminary observations from a high-volume transplant centre.

BACKGROUND: Patients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this cohort of high-risk patients. We hypothesized that LGE has high prognostic value in primary DCM patients referred for possible transplantation/left ventricular assist device (LVAD) consideration. METHODS: Over 49 consecutive months, 61 consecutives DCM patients were referred for standard CMR(1.5T, GE) to interrogate the LV pattern, distribution, and extent of LGE (MultiHance, Princeton, NJ). Inclusion criteria for a primary non-ischaemic DCM and EF <45% were met in 31 patients. DCM patients were categorized into: (i) presence of midwall LV stripe (+Stripe) and (ii) absence of midwall stripe (-Stripe) groups. Primary outcome was defined by the composite of death, need for LV assist device (LVAD), and urgent orthotopic cardiac transplantation (Tx) during a 12-month follow-up period. Kaplan-Meier survival analysis was conducted grouping patients by +Stripe and -Stripe. RESULTS: There were no differences between groups for demographics, blood pressure, labs, baseline LVEF, NYHA class, or invasive haemodynamics. There were 18 patients (58%) with +Stripe. Nine events occurred: seven patients required urgent Tx and/or LVAD implantation and two patients died. The +Stripe categorization strongly predicted the need for LVAD, urgent Tx surgery, and death (log-rank = 9, P = 0.002). All the events occurred in the +Stripe patients with no MACE experienced in the -Stripe group. The -Stripe group experienced marked signs of improvement in LVEF (P = 0.01) at follow-up. LVEDD was predictive of need for LVAD/Tx and death by univariate analysis. Otherwise, no common clinical metric such as LVEF, LVEDV, RVEF, RVEDV, or any invasive haemodynamic parameter predicted MACE. CONCLUSIONS: The presence of +Stripe on CMR is strongly predictive of LVAD, transplant need, and death during a 12-month follow-up period in DCM patients in this proof of concept study. All -Stripe patients survived without experiencing any events. Incorporating CMR imaging into routine clinical practice may have prognostic value in DCM patients; indicating conservative management in low-risk patients while expectantly managing high-risk patients.

Anginal symptoms, coronary artery disease, and adverse outcomes in Black and White women: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

BACKGROUND: Black women are less likely to be evaluated and treated for anginal symptoms, despite a higher premature cardiac mortality rate compared to white women. Our objective was to compare angina symptoms in black versus white women regarding (1) angina symptoms characterization; (2) relationship with obstructive coronary artery disease (CAD); and (3) relationship with subsequent mortality. METHODS: A cohort of 466 women (69 black and 397 white) undergoing coronary angiography for suspected ischemia and without prior history of CAD completed symptom checklists. Four symptom clusters (CHEST, UPPER, STOMACH, and TYPICAL TRIGGERS) were derived by factor analysis. All angiograms were analyzed by core lab. Mortality data over 10 years were obtained from National Death Index. RESULTS: (1) Black women had lower mean CHEST cluster scores (0.60±0.30 vs. 0.73±30, p=0.002), but higher STOMACH scores (0.41±0.25 vs. 0.30±0.25, p=0.011) than white women. (2) Prevalence and severity of CAD did not differ in black and white women and was not predicted by symptom cluster scores. (3) All-cause mortality rates were 24.9% in blacks versus 14.5% in whites, p=0.007; and cardiovascular mortality 22.5% vs.8.8%, p=0.001. Symptom clusters were not predictive of adverse events in white women. However, black women with a low TYPICAL score had significantly higher mortality compared to those with a high TYPICAL score (43% vs. 10%, p=0.006). CONCLUSIONS: Among women undergoing coronary angiography, black women report fewer chest-related and more stomach-related symptoms, regardless of presence or severity of CAD, and these racial symptom presentation differences are linked with the more adverse prognosis observed in the black women. Atypical symptom presentation may be a barrier to appropriate and timely diagnosis and treatment and contribute to poorer outcomes for black women.

Left Ventricular Energy Model Predicts Adverse Events in Women With Suspected Myocardial Ischemia: Results From The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study.

OBJECTIVES: To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. BACKGROUND: The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. METHODS: Women (n=227, mean age 59±12 years, range 31-86), with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n= 207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. RESULTS: Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, p<0.005) and IEU and systolic blood pressure by gated SEPCT (Chi-squared 34, p<0.005). The models remained predictive after adjustment for age, disease history and Framingham risk score. For each Cox model, patients were categorized as high-risk if the model hazard was positive and not high-risk otherwise. Kaplan-Meier analysis of time to MACE was performed for high-risk vs. not high-risk for MR (log rank 25.3, p<0.001) and gated SEPCT (log rank 18.2, p<001) models. CONCLUSIONS: Among women with suspected myocardial ischemia a high internal energy utilization has higher prognostic value than either a low EF or the presence of a myocardial perfusion defect assessed using two independent modalities of MR or gated SPECT.

Is there an alternative explanation to post-myocardial infarction emergence of mitral regurgitation? A CMR-LGE observational study.

BACKGROUND AND AIM OF THE STUDY: Post-myocardial infarction (MI) mitral regurgitation (MR) is thought to be due to a passive, rather than active, remodeling of the mitral valve apparatus and its relationship with other cardiac structures that contribute to MR. Standard contrast-enhanced magnetic resonance (CMR) late gadolinium enhancement (LGE) may be sensitive to non-myocardial pathology involving the mitral valve leaflets. It was hypothesized that the presence of mitral valve enhancement (MVE) on LGE imaging in post-MI patients would be associated with an increased incidence of MR. METHODS: The presence or absence of MVE was noted in patients presenting for CMR with MI and non-MI indications requiring LGE. A chi-square analysis was performed for non-contiguous variables; SPSS (Chicago) software was utilized for the statistical analysis. RESULTS: Eighty-seven patients (54 males, 33 females) underwent LGE-CMR studies utilizing a 1.5 T GE scanner with MultiHance gadolinium contrast administration. LGE+ (present) was noted in 68 patients, and LGE- (absent) in 19 patients. Post-MI patterns of LGE+ were noted in 51 patients and LGE-in 36 patients; MVE+ was noted in 39 patients and MVE- in 48; and MR+ was present in 67 patients and absent (MR-) in 20 patients. MVE was observed chiefly in post-MI patients (33/51; 65%) and infrequently in non-post-MI patients (6/36; 17%; chi2 = 17.8, p < 0.001, power = 0.995). Further, MR was present more frequently in patients with MVE (36/39; 92%) compared to patients without MVE (31/48; 65%; chi2 = 7.8, p = 0.005, power = 0.814). CONCLUSION: MVE is present in a large number of post-MI patients but rarely in non-post-MI patients. Post-MI patients with, rather than without, MVE are far more likely to have MR. These observations suggest a specific but as-yet unknown reactive process that may contribute to mitral leaflet remodeling in post-MI patients, potentially contributing to an increased incidence of MR in post-MI patients.

Combining psychosocial data to improve prediction of cardiovascular disease risk factors and events: The National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation study.

BACKGROUND: There is overlap among psychosocial predictors of cardiovascular disease (CVD). The usefulness of combining psychosocial variables as risk markers for CVD needs investigation. METHODS: Participants were 493 women in the NHLBI WISE study. Multivariate combination of Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Social Network Index (SNI), and Cook-Medley hostility subscales was evaluated, and principal components analysis also conducted. Relationships of composite psychosocial risk markers to CVD events and risk factors were assessed. RESULTS: The multivariate block of SNI, Cook-Medley Hostile Affect subscale, STAI, and BDI predicted CVD events (χ(2) = 27.8, df = 6, p < .001). Scalewise factor analysis revealed 2 factors: negative affectivity (NA) and hostility (explained variance, 45.6% and 17.1%, respectively). NA was associated with BMI (ß [SE] = 0.18 [0.09], p = .04), hostility with metabolic syndrome (exp(ß) = 0.60 [0.28], p = .04). Both factors were associated with blood pressure (BP): NA with SBP (ß = 2.53 [1.04], p = .02) and DBP (ß = 1.66 [0.60], p = .02); hostility with SBP (ß = 2.72 [1.13], p = .02) and DBP (ß = 1.83 [0.65], p = .005). Neither factor predicted CVD events. Original scales predicted CVD events: lower SNI (HR = 0.74, CI = 0.57-0.96), lower Hostile Affect (HR = 0.80, CI = 0.56-1.03), and higher BDI (HR = 1.33, CI = 1.08-1.74). CONCLUSIONS: In women with suspected ischemia, multivariate combination of psychosocial risk markers predicts CVD events; derived psychosocial factors were associated with CVD risk factors but not events. Measuring common variance among psychosocial variables may be a useful research strategy.

Relationships between cardiovascular disease risk factors and depressive symptoms as predictors of cardiovascular disease events in women.

BACKGROUND: Modifiable risk factors for cardiovascular disease (CVD) account for much of the variability in CVD outcomes and are also related to psychosocial variables. There is evidence that depression can undermine the treatment and advance the progression of CVD risk factors, suggesting that CVD risk factor relationships with CVD events may differ among those with depression. METHODS: This study tracked CVD events and mortality over a median of 5.9 years among a prospective cohort of 620 women (mean age 59.6 years [11.6]) completing a diagnostic protocol including coronary angiography and CVD risk factor assessment. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). The study outcome was combined cardiovascular mortality and events. RESULTS: Over the follow-up interval, 16.1% of the sample experienced one or more of the cardiovascular outcomes. In separate Cox regression models adjusting for age, education history, ethnicity, and coronary angiogram scores, we observed statistically significant CVD risk factor × BDI score interactions for diabetes, smoking, and waist-hip ratio factors. Simple effect analyses indicated that diabetes and smoking status were more strongly associated with cardiovascular outcomes among participants with lower BDI scores, whereas waist-hip ratio values predicted outcomes only among those with higher BDI scores. CONCLUSIONS: These results suggest that the relationship between modifiable CVD risk factors and CVD outcomes may vary with depression status in clinical samples of women. This evidence augments prior research by demonstrating that depression may influence CVD risk jointly with or independent of CVD risk factors. It also provides further support for the inclusion of depression assessment in cardiovascular clinic settings.

LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association.

BACKGROUND: In patients with severe aortic stenosis (AS), long-term data tracking surgically induced effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiovascular MRI (CMR) offers the ability to serially track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability. HYPOTHESIS: We hypothesize that changes in LV structure and function following aortic valve replacement (AVR) are detectable by CMR and once triggered by AVR, continue for an extended period. METHODS: Twenty-four patients of which ten (67 ± 12 years, 6 female) with severe, but compensated AS underwent CMR pre-AVR, 6 months, 1 year and up to 4 years post-AVR. 3D LV mass index, volumetrics, LV geometry, and EF were measured. RESULTS: All patients survived AVR and underwent CMR 4 serial CMR's. LVMI markedly decreased by 6 months (157 ± 42 to 134 ± 32 g/m2, p < 0.005) and continued trending downwards through 4 years (127 ± 32 g/m2). Similarly, EF increased pre to post-AVR (55 ± 22 to 65 ± 11%,(p < 0.05)) and continued trending upwards, remaining stable through years 1-4 (66 ± 11 vs. 65 ± 9%). LVEDVI, initially high pre-AVR, decreased post-AVR (83 ± 30 to 68 ± 11 ml/m2, p < 0.05) trending even lower by year 4 (66 ± 10 ml/m2). LV stroke volume increased rapidly from pre to post-AVR (40 ± 11 to 44 ± 7 ml, p < 0.05) continuing to increase non-significantly through 4 years (49 ± 14 ml) with these LV metrics paralleling improvements in NYHA. However, LVmass/volume, a 3D measure of LV geometry, remained unchanged over 4 years. CONCLUSION: After initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. Via CMR, surgically induced benefits to LV structure and function are durable and, unexpectedly express continued, albeit markedly incomplete improvement through 4 years post-AVR concordant with sustained improved clinical status. This supports down-regulation of both mRNA and MMP activity acutely with robust suppression long term.

Prognostic value of global MR myocardial perfusion imaging in women with suspected myocardial ischemia and no obstructive coronary disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study.

OBJECTIVES: The purpose of this study was to assess the prognostic value of global magnetic resonance (MR) myocardial perfusion imaging (MPI) in women with suspected myocardial ischemia and no obstructive (stenosis <50%) coronary artery disease (CAD). BACKGROUND: The prognostic value of global MR-MPI in women without obstructive CAD remains unknown. METHODS: Women (n = 100, mean age 57 ± 11 years, age range 31 to 76 years), with symptoms of myocardial ischemia and with no obstructive CAD, as assessed by coronary angiography, underwent MR-MPI and standard functional assessment. During follow-up (34 ± 16 months), time to first adverse event (death, myocardial infarction, or hospitalization for worsening anginal symptoms) was analyzed using global MPI and left ventricular ejection fraction (EF) data. RESULTS: Adverse events occurred in 23 (23%) women. Using univariable Cox proportional hazards regression modeling, variables found to be predictive of adverse events were global MR-MPI average uptake slope (p < 0.05), the ratio of MR-MPI peak signal amplitude to uptake slope (p < 0.05), and EF (p < 0.05). Two multivariable Cox models were formed, 1 using variables that were performance site dependent: ratio of MR-MPI peak amplitude to uptake slope together with EF (chi square: 13, p < 0.005); and a model using variables that were performance site independent: MR-MPI slope and EF (chi square: 12, p < 0.005). Each of the 2 multivariable models remained predictive of adverse events after adjustment for age, disease history, and Framingham risk score. For each of the Cox models, patients were categorized as high risk if they were in the upper quartile of the model and as not high risk otherwise. Kaplan-Meier analysis of time to event was performed for high risk versus not high risk for site-dependent (log rank: 15.2, p < 0.001) and site-independent (log rank: 13.0, p < 001) models. CONCLUSIONS: Among women with suspected myocardial ischemia and no obstructive CAD, MR-MPI-determined global measurements of normalized uptake slope and peak signal uptake, together with global functional assessment of EF, appear to predict prognosis.

DHEA-S levels and cardiovascular disease mortality in postmenopausal women: results from the National Institutes of Health--National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE).

CONTEXT: Dehydroepiandrosterone sulfate (DHEA-S), a major circulating sex steroid prohormone, declines with age. Low levels have been associated with increased cardiovascular disease (CVD) risk and all-cause mortality, although these results have not been consistently replicated, particularly in women. OBJECTIVE: Our objective was to examine the association of circulating DHEA-S levels, CVD, and mortality risk among postmenopausal women with suspected myocardial ischemia. DESIGN: In the Women's Ischemia Syndrome Evaluation, 270 postmenopausal women underwent coronary angiography and blood hormone levels for suspected ischemia and were followed annually. The primary outcome of interest was CVD mortality; secondary analyses included all-cause mortality and nonfatal CVD events (myocardial infarction, stroke, and congestive heart failure) and angiographic obstructive coronary artery disease (CAD). RESULTS: Women in the lowest DHEA-S tertile had higher CVD mortality (17% 6-yr mortality rate vs. 8%; log-rank P = 0.011), and all-cause mortality (21 vs. 10%; P = 0.011) compared with women with higher DHEA-S levels. The increased CVD mortality risk [hazard ratio (HR) = 2.55; 95% confidence interval (CI) = 1.19-5.45] remained unchanged after adjustment for multiple CVD risk factors (HR = 2.43; 95% CI = 1.06-5.56) but became nonsignificant when further adjusting for the presence or severity of angiographic obstructive CAD (HR = 1.99; 95% CI = 0.87-4.59). Results were similar for all-cause mortality. Lower DHEA-S levels were only marginally but not independently associated with obstructive CAD. CONCLUSIONS: Among postmenopausal women with coronary risk factors undergoing coronary angiography for suspected myocardial ischemia, lower DHEA-S levels were linked with higher CVD mortality and all-cause mortality. Our study provides valuable feasibility data useful for future investigations and possible mechanistic pathways.

Self-rated versus objective health indicators as predictors of major cardiovascular events: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

OBJECTIVE: To determine the association between self-rated health and major cardiovascular events in a sample of women with suspected myocardial ischemia. Previous studies showed that self-rated health is a predictor of objective health outcomes, such as mortality. METHOD: At baseline, 900 women rated their health on a 5-point scale ranging from poor to excellent as part of a protocol that included quantitative coronary angiography, cardiovascular disease (CVD) risk factor assessment, cardiac symptoms, psychotropic medication use, and functional impairment. Participants were followed for a maximum of 9 years (median, 5.9 years) to determine the prevalence of major CVD events (myocardial infarction, heart failure, stroke, and CVD-related death). RESULTS: A total of 354 (39.3% of sample) participants reported their health as either poor or fair. After adjusting for demographic factors, CVD risk factors, and coronary artery disease severity, women who rated their health as poor (hazard ratio, 2.1 [1.1-4.2]) or fair (hazard ratio, 2.0 [1.2-3.6]) experienced significantly shorter times to major CVD events compared with women who rated their health as excellent or very good. Further adjustment for functional impairment, however, attenuated the self-rated health relationships with major CVD events. CONCLUSIONS: Among women with suspected myocardial ischemia, self-rated health predicted major CVD events independent of demographic factors, CVD risk factors, and angiogram-defined disease severity. However, functional impairment seemed to explain much of the self-rated health association. These results support the clinical utility of self-rated health scores in women and encourage a multidimensional approach to conceptualizing these measures.

Comorbid depression and anxiety symptoms as predictors of cardiovascular events: results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

OBJECTIVE: To study the independent and interactive effects of depression and anxiety symptoms as predictors of cardiovascular disease (CVD) events in a sample of women with suspected myocardial ischemia. Symptoms of depression and anxiety overlap strongly and are independent predictors of CVD events. Although these symptoms commonly co-occur in medical patients, little is known about combined effects of depression and anxiety on CVD risk. METHOD: A total of 489 women completed a baseline protocol including coronary angiogram, CVD risk factor assessment, and questionnaire-based measures of depression and anxiety symptoms, using the Beck Depression Inventory (BDI) and State Trait Anxiety Inventory (STAI), respectively. Participants were followed for a median 5.9 years to track the prevalence of CVD events (stroke, myocardial infarction, heart failure, and CVD-related mortality). We tested the BDI x STAI interaction effect in addition to the BDI and STAI main effects. RESULTS: Seventy-five women (15.3% of sample) experienced a CVD event, of which 18 were deaths attributed to cardiovascular causes. Results using Cox regression indicated a significant BDI x STAI interaction effect in the prediction of CVD events (p = .02) after covariate adjustment. Simple effect analyses indicated that depression scores were significant predictors of CVD events among women with low anxiety scores (hazard ratio [HR] = 2.3 [in standard deviation units]; 95% Confidence Interval [CI] = 1.3-3.9; p = .005) but not among women with higher levels of anxiety (HR = 0.99; 95% CI = 0.70-1.4; p = .95). CONCLUSION: Among women with suspected myocardial ischemia, the value of depression symptoms for predicting CVD events varied by the severity of comorbid anxiety. These results suggest that the clinical utility of depression measures may be improved by using them in combination with measures of anxiety.

Characteristics and outcomes of trauma patients with ICU lengths of stay 30 days and greater: a seven-year retrospective study.

INTRODUCTION: Prolonged intensive care unit lengths of stay (ICU LOS) for critical illness can have acceptable mortality rates and quality of life despite significant costs. Only a few studies have specifically addressed prolonged ICU LOS after trauma. Our goals were to examine characteristics and outcomes of trauma patients with LOS >or= 30 days, predictors of prolonged stay and mortality. METHODS: All trauma ICU admissions over a seven-year period in a level 1 trauma center were analyzed. Admission characteristics, pre-existing conditions and acquired complications in the ICU were recorded. Logistic regression was used to identify independent predictors of prolonged LOS and predictors of mortality among those with prolonged LOS after univariate analyses. RESULTS: Of 4920 ICU admissions, 205 (4%) had ICU LOS >30 days. These patients were older and more severely injured. Age and injury severity score (ISS) were associated with prolonged LOS. After logistic regression analysis, sepsis, acute respiratory distress syndrome, and several infectious complications were important independent predictors of prolonged LOS. Within the group with ICU LOS >30 days, predictors of mortality were age, pre-existing renal disease as well as the development of renal failure requiring dialysis. Overall mortality was 12%. CONCLUSIONS: The majority of patients with ICU LOS >or= 30 days will survive their hospitalization. Infectious and pulmonary complications were predictors of prolonged stay. Further efforts targeting prevention of these complications are warranted.

The joint impact of smoking and exercise capacity on clinical outcomes among women with suspected myocardial ischemia: the WISE study.

BACKGROUND: Although extensive research has been conducted on both smoking and low exercise capacity alone, few studies have examined the joint impact or interaction of these two risk factors. We examined the joint and interactive effects of smoking and self-reported exercise capacity on subsequent clinical events (heart failure, myocardial infarction [MI], stroke, and cardiovascular-related mortality) among women with suspected myocardial ischemia. METHODS: At baseline (1996-1999), 789 women completed angiographic testing of coronary artery disease (CAD) severity and provided self-report information about their smoking history and exercise capacity as well as demographic and other risk factor data. Incidence of clinical events among the women was tracked for a median of 5.9 years; this analysis was conducted in 2008. RESULTS: In an adjusted survival analysis, women with a positive smoking history and self-reported low exercise capacity had the greatest risk of experiencing a clinical event (HR = 7.7, 95% CI 2.3, 25.5), followed by women with a positive smoking history and self-reported high exercise capacity (HR = 6.9, 95% CI 2.0, 24.6) and those with a negative smoking history and self-reported low exercise capacity (HR = 4.9, 95% CI 1.5, 15.8), relative to women with a negative smoking history and self-reported high exercise capacity. Additional analyses revealed a significant interaction between smoking history and exercise capacity, such that (1) women with a positive smoking history did not experience an additional significantly greater risk due to low exercise capacity, unlike those with a negative smoking history, and (2) all women experienced a significantly greater risk due to a positive smoking history regardless of their exercise capacity. CONCLUSIONS: Among women with suspected myocardial ischemia, the combined protective health effects of self-reported high exercise capacity and a negative smoking history remained significant after controlling for preexisting CAD severity and other established risk factors. These findings highlight the importance of studying behavioral risk factors in combination.

The triglyceride/high-density lipoprotein cholesterol ratio predicts all-cause mortality in women with suspected myocardial ischemia: a report from the Women's Ischemia Syndrome Evaluation (WISE).

UNLABELLED: High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are important cardiovascular risk factors in women. The prognostic utility of the TG/HDL-C ratio, a marker for insulin resistance and small dense low-density lipoprotein particles, is unknown among high-risk women. METHODS: We studied 544 women without prior myocardial infarction or coronary revascularization, referred for clinically indicated coronary angiography and enrolled in the Women's Ischemia Syndrome Evaluation (WISE). Fasting lipid profiles and detailed demographic and clinical data were obtained at baseline. Multivariate Cox-proportional hazards models for all-cause mortality and cardiovascular events (death, myocardial infarction, heart failure, stroke) over a median follow-up of 6 years were constructed using log TG/HDL-C ratio as a predictor variable and accounting for traditional cardiovascular risk factors. RESULTS: Mean age was 57 +/- 11 years; 84% were white, 55% hypertensive, 20% diabetic, 50% current or prior smokers. Triglyceride/HDL-C ranged from 0.3 to 18.4 (median 2.2, first quartile 0.35 to <1.4, fourth quartile 3.66-18.4). Deaths (n = 33) and cardiovascular events (n = 83) increased across TG/HDL-C quartiles (both P < .05 for trend). Triglyceride/HDL-C was a strong independent predictor of mortality in models adjusted for age, race, smoking, hypertension, diabetes, and angiographic coronary disease severity (hazard ratio 1.95, 95% CI 1.05-3.64, P = .04). For cardiovascular events, the multivariate hazard ratio was 1.54 (95% CI 1.05-2.22, P = .03) when adjusted for demographic and clinical variables, but became nonsignificant when angiographic results were included. CONCLUSION: Among women with suspected ischemia, the TG/HDL-C ratio is a powerful independent predictor of all-cause mortality and cardiovascular events.

Depression and cardiovascular health care costs among women with suspected myocardial ischemia: prospective results from the WISE (Women's Ischemia Syndrome Evaluation) Study.

OBJECTIVES: This study evaluated 3 novel questions in a prospective clinical cohort of women undergoing evaluation for suspected myocardial ischemia: 1) What is the relationship between depression and cardiovascular costs? 2) Does the relationship vary by definition of depression? 3) Do depression-cost relationship patterns differ among women with versus without coronary artery disease (CAD)? BACKGROUND: Comorbid depression has been linked to higher medical costs in previous studies of cardiovascular patients. METHODS: A total of 868 women presenting with suspected myocardial ischemia completed an extensive baseline examination including cardiovascular risk factor assessment and coronary angiogram. Depression was defined by: 1) current use of antidepressants; 2) a reported history of depression treatment; and 3) Beck Depression Inventory scores. Direct (hospitalizations, office visits, procedures, and medications) and indirect (out-of-pocket, lost productivity, and travel) costs were collected through 5 years of follow-up to estimate cardiovascular costs. RESULTS: Using the study criteria, 17% to 45% of the women studied met study depression criteria. Depressed women showed adjusted annual cardiovascular costs $1,550 to $3,300 higher than nondepressed groups (r = 0.08 to 0.12, p < 0.05). Depression-cost relationships also varied by CAD status, with stronger associations present among women without evidence of significant CAD. CONCLUSIONS: Depression was associated with 15% to 53% increases in 5-year cardiovascular costs, and cost differences were present using 3 definitions of depression. The results reinforce the importance of assessing depression in clinical populations and support the hypothesis that improved management of depression in women with suspected myocardial ischemia could reduce medical costs.

Routine evaluation of left ventricular diastolic function by cardiovascular magnetic resonance: a practical approach.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has excellent capabilities to assess ventricular systolic function. Current clinical scenarios warrant routine evaluation of ventricular diastolic function for complete evaluation, especially in congestive heart failure patients. To our knowledge, no systematic assessment of diastolic function over a range of lusitropy has been performed using CMR. METHODS AND RESULTS: Left ventricular diastolic function was assessed in 31 subjects (10 controls) who underwent CMR and compared with Transthoracic echocardiogram (TTE) evaluation of mitral valve (MV) and pulmonary vein (PV) blood flow. Blood flow in the MV and PV were successfully imaged by CMR for all cases (31/31,100%) while TTE evaluated flow in all MV (31/31,100%) but only 21/31 PV (68%) cases. Velocities of MV flow (E and A) measured by CMR correlated well with TTE (r = 0.81, p < 0.001), but demonstrated a systematic underestimation by CMR compared to TTE (slope = 0.77). Bland-Altman analysis of the E:A ratio and deceleration time (DT) calculated from each modality showed excellent agreement (bias -0.29, and -10.3 ms for E:A and DT, respectively). When assessing morphology using TTE, CMR correctly identified patients as having normal or abnormal inflow conditions. CONCLUSION: We have shown that there is homology between CMR and TTE for the assessment of diastolic inflow over a wide range of conditions, including normal, impaired relaxation and restrictive. There is excellent agreement of quantitative velocity measurements between CMR and TTE. Diastolic blood flow assessment by CMR can be performed in a single scan, with times ranging from 20 sec to 3 min, and we show that there is good indication for applying CMR to assess diastolic conditions, either as an adjunctive test when evaluating systolic function, or even as a primary test when TTE data cannot be obtained.

Lipid-lowering medication use and aggression scores in women: a report from the NHLBI-sponsored WISE study.

AIM: The aim of this study was to examine the association between the use of lipid-lowering medication and aggressive responding, hostility, cynicism, and depression scores in women undergoing coronary angiography. METHODS: The cohort included 498 women from the National Heart, Lung and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. WISE is a four-center study of women with chest pain who underwent quantitative coronary angiography for suspected myocardial ischemia. The psychosocial indices included the Cook Medley Hostility questionnaire, measuring aggression, hostility, and cynicism, and the Beck Depression Inventory (BDI). RESULTS: Compared to those not on lipid-lowering medication, women receiving lipid-lowering pharmacotherapy were older (62 vs. 55 years, p < 0.001) and had more hypertension, dyslipidemia, diabetes, and coronary artery disease (CAD, defined as > or =50% stenoses in at least one epicardial artery) (all p < 0.003). Women on lipid-lowering medication had higher aggressive responding scores than those not on medication, 3.0 +/- 1.8 vs. 2.7 +/- 1.7, respectively (age-adjusted p < 0.003). This association persisted after adjustment for coronary risk factors, education, and extent of angiographic disease (CAD) (p < 0.005), and after exclusion of women using psychotropic medications (p < 0.001). Hostility, cynicism, and depression scores did not differ by medication use.

Anger, hostility, and cardiac symptoms in women with suspected coronary artery disease: the Women's Ischemia Syndrome Evaluation (WISE) Study.

OBJECTIVE: To determine the relationship of anger and hostility to angiographic coronary artery disease (CAD), symptoms, and functional status among women with suspected CAD. METHODS: Data were collected from 636 women with suspected CAD referred for diagnostic angiography in the Women's Ischemia Syndrome Evaluation (WISE) Study. CAD was assessed as angiographic presence/absence of disease (> or =50% stenosis in any epicardial coronary artery). Hostility/anger, angina, symptoms, and functional status were assessed by the Cook-Medley Hostility Inventory, Spielberger Anger Expression Scale, cardiovascular symptom history, and the Duke Activity Status Index. RESULTS: Logistic regression revealed that anger-out (i.e., aggressive behavior in response to angry feelings) was independently associated with the presence/absence of angiographic CAD (OR = 1.09, CI 1.01-1.17). Anger and hostility were higher among women reporting increased cardiovascular symptoms. In women without angiographic CAD, those with nonanginal cardiac symptoms had the highest anger-out, anger expression, hostile affect, and aggressive responding scores, and those with typical angina reported the lowest functional status. Among women with CAD, functional status was lowest in women with atypical angina. CONCLUSIONS: Among women with suspected CAD, anger-out scores were associated with the presence of angiographic CAD. Anger/hostility traits were associated with increased symptoms, particularly with nonanginal chest pain in women without angiographic CAD. Relationships among psychosocial factors, cardiac symptoms, and angiographic CAD are potentially important in the management of women with suspected CAD.

Physiologic compensation is supranormal in compensated aortic stenosis: does it return to normal after aortic valve replacement or is it blunted by coexistent coronary artery disease? An intramyocardial magnetic resonance imaging study.

BACKGROUND: In compensated aortic stenosis (AS), cardiac performance measured at the ventricular chamber is typically supranormal, whereas measurements at the myocardium are often impaired. We investigated intramyocardial mechanics after aortic valve replacement (AVR) and the effects relative to the presence or absence of coronary artery disease (CAD+ or CAD-), respectively. METHODS AND RESULTS: Twenty-nine patients (46 to 91 years, 10 female) with late but not decompensated AS underwent cardiovascular MRI before AVR (PRE), with follow-up at 6+/-1 (EARLY) and 13+/-2 months (LATE) to determine radiofrequency tissue-tagged left ventricle (LV) transmural circumferential strain, torsion, structure, and function. At the myocardial level, concentric LV hypertrophy regressed 18% LATE (93+/-22 versus 77+/-17 g/m2; P<0.0001), whereas at the LV chamber level, ejection fraction was supranormal PRE, 67+/-6% (ranging as high as 83%) decreasing to 59+/-6% LATE (P<0.05), representing not dysfunction but a return to more normal LV physiology. Between the CAD+ and CAD- groups, intramyocardial strain was similar PRE (19+/-10 versus 20+/-10) but different LATE, with dichotomization specifically related to the CAD state. In the CAD- patients, strain increased to 23+/-10% (+20%), whereas in CAD+ patients it fell to 16+/-11% (-26%), representing a nearly 50% decline after AVR (P<0.05). This was particularly evident at the apex, where CAD- strain LATE improved 17%, whereas for CAD+ it decreased 2.5-fold. Transmural strain and myocardial torsion followed a similar pattern, critically dependent on CAD. AVR impacted LV geometry and mitral apparatus, resulting in decreased mitral regurgitation, negating the double valve consideration. CONCLUSIONS: In AS patients after AVR, reverse remodeling of the supranormal systolic function parallels improvement in cardiovascular MRI-derived regression of LV hypertrophy and LV intramyocardial strain. However, discordant effects are evident after AVR, driven by CAD status, suggesting that the typical AVR benefits are experienced disproportionately by those without CAD and not by those obliged to undergo concomitant coronary artery bypass grafting/AVR.

Gender as a risk factor for contrast nephropathy: effects of hydration and N-acetylcysteine.

BACKGROUND: In a few studies, N-acetylcysteine has been shown to prevent contrast-induced nephropathy in patients with chronic, stable renal failure undergoing elective procedures. Other studies have shown variable outcomes. Furthermore, the majority of prior studies have mainly studied men, and gender as a risk factor has not been studied. HYPOTHESIS: The study sought to evaluate the effectiveness of N-acetylcysteine and hydration in unselected patients with both acute and stable renal insufficiency (RI) undergoing urgent or elective cardiac or peripheral angiography. METHODS: We evaluated records of 146 patients with RI undergoing angiography. We compared patients receiving periprocedure hydration and acetylcysteine with patients who were only hydrated or received no pretreatment. We evaluated the 48-h change in serum creatinine between groups and further analyzed the effect of hydration and gender on outcomes. RESULTS: Demographics and baseline creatinine were similar between groups. Post procedure, the creatinine increased significantly in both groups, but less so in the acetylcysteine group (control: 0.35 +/- 0.08 mg/dl; acetylcysteine: 0.14 +/- 0.04 mg/dl, p < 0.05). When the control group was further stratified by hydration, the increase in creatinine for the hydrated patients was only 0.17 +/- 0.10 mg/dl compared with 0.54 +/- 0.12 mg/dl in patients with inadequate hydration. In the control group, women were more likely to receive no preprocedural hydration (59 vs. 40%), had a bigger rise in creatinine, received less protection from hydration alone, but were equally well protected by hydration plus acetylcysteine. In the acetylcysteine group, change in creatinine for women was minimal (+ 0.14 +/- 0.07 mg/dl) and not different from men (+ 0.15 +/- 0.05). CONCLUSION: Unselected patients with acute and chronic RI had no benefit from acetylcysteine beyond that seen with hydration alone. Gender may be a risk factor for contrast-induced nephropathy, with hydration offering less protection in women. Acetylcysteine (with hydration) seems to minimize the gender difference.