Diane V Thompson

Contrast-enhanced CMR is equally effective as TEE in the evaluation of left atrial appendage thrombus in patients with atrial fibrillation undergoing pulmonary vein isolation procedure

BACKGROUND Patients with atrial fibrillation (AF) routinely undergo transesophageal echocardiography (TEE) for the evaluation of the left atrial appendage (LAA) to rule out thrombus prior to undergoing pulmonary vein isolation (PVI). Cardiac magnetic resonance (CMR) is now increasingly used for the evaluation of patients with AF to define pulmonary vein (PV) anatomy prior to PVI. OBJECTIVE To hypothesize that a retrospective comparison of 2-dimensional/3-dimensional (2D/3D) contrast-enhanced CMR sequences with TEE for the evaluation of LAA thrombus in patients with AF selected for PVI will demonstrate equivalence. METHODS Ninety-seven (N = 97) consecutive patients with AF underwent near-simultaneous TEE and noncontrast and contrast CMR prior to undergoing an initial PVI procedure. The CMR images were analyzed in 2 categories: (1) the 2D noncontrast cine images and early gadolinium enhancement images showing LAA and (2) 3D contrast source images acquired during PV magnetic resonance angiography. CMR variables evaluated were the presence or absence of LAA thrombus and the quality of images, and they were compared with the results of TEE in a blinded fashion. RESULTS All subjects were analyzed for the presence or absence of LAA thrombus. Thrombus was absent in 98% of the patients on both TEE and CMR and present in 2% on both studies (100% correlation). In 6 subjects, 2D cine CMR images were indeterminate whereas all 2D early gadolinium enhancement images and 3D contrast images were successful in excluding LAA thrombus. There was 100% concordance between CMR and TEE for the final diagnosis of LAA thrombus. CONCLUSIONS In one single examination, CMR offers a comparable alternative to TEE for the complete noninvasive evaluation of LAA thrombus and PV anatomy in patients with AF referred for PVI without obligate need for TEE.

Cardiovascular and Mortality Risk of Apparent Resistant Hypertension in Women With Suspected Myocardial Ischemia: A Report From the NHLBI-Sponsored WISE Study

Background Women are more likely than men to develop resistant hypertension, which is associated with excess risk of major adverse outcomes; however, the impact of resistant hypertension in women with ischemia has not been explicitly studied. In this Womens Ischemia Syndrome Evaluation (WISE) analysis, we assessed long‐term adverse outcomes associated with apparent treatment‐resistant hypertension (aTRH) among women with suspected myocardial ischemia referred for coronary angiography. Methods and Results Women (n=927) were grouped according to baseline blood pressure (BP): normotensive (no hypertension history, BP <140/90 mm Hg, no antihypertensive drugs); controlled (BP <140/90 mm Hg and a hypertension diagnosis or on 1 to 3 drugs); uncontrolled (BP ≥140/90 mm Hg on ≤2 drugs); or aTRH (BP ≥140/90 mm Hg on 3 drugs or anyone on ≥4 drugs). Adverse outcomes (first occurrence of death [any cause], nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure or angina) were collected over 10 years of follow‐up. Apparent treatment‐resistant hypertension prevalence was 10.4% among those with hypertension. Women with aTRH had a greater incidence of adverse outcomes, compared with normotensive women (adjusted hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.94 to 5.43), and women with controlled (HR, 1.77; 95% CI, 1.26 to 2.49) and uncontrolled (HR, 1.62; 95% CI, 1.15 to 2.27) hypertension; outcome differences were evident early in follow‐up. Risk of all‐cause death was greater in the aTRH group, compared to the normotensive women and women with controlled and uncontrolled hypertension. Conclusions In this cohort of women with evidence of ischemia, aTRH was associated with a profoundly increased long‐term risk of major adverse events, including death, that emerged early during follow‐up.

Menopausal symptoms and cardiovascular disease mortality in the Women's Ischemia Syndrome Evaluation (WISE).

Objective: Studies have linked vasomotor symptoms (VMS) to markers of cardiovascular disease (CVD) risk, yet few have considered clinical cardiovascular events. Data suggest that associations may depend upon the age that symptoms occur. We examined associations between VMS and cardiovascular events and endothelial function, considering age of symptom onset. Methods: The Womens Ischemia Syndrome Evaluation enrolled women referred for coronary angiography for suspected myocardial ischemia. A total of 254 women aged more than 50 years, postmenopausal, with both ovaries, not taking hormone therapy underwent a baseline evaluation, were followed annually (median = 6.0 y), and the National Death Index was searched to ascertain CVD mortality (median = 9.3 y). A subset of participants underwent brachial artery ultrasound for flow-mediated dilation (FMD). Receiver-operating curve analysis was used to determine vasomotor symptom groups (symptoms beginning < age 42 [early onset], beginning ≥42 [later onset], never) which were examined in relation to cardiovascular events and FMD in Cox proportional hazard and linear regression models. Results: Women reporting early onset VMS (HR = 3.35, 95% CI = 1.23-7.86, P = 0.005) and women who never had VMS (HR = 2.17, 95% CI = 1.02-4.62, P = 0.05) had higher CVD mortality than women with later onset symptoms (multivariable models). Women with early onset VMS had lower FMD than women with later onset symptoms (b = −4.31, SE = 2.10, P = 0.04, multivariable). Conclusions: Women with signs and symptoms of ischemia who had VMS beginning early in midlife had higher CVD mortality and reduced endothelial function relative to women with later onset symptoms. Future research should evaluate the vascular phenotype of women with early midlife VMS.

Anxiety associations with cardiac symptoms, angiographic disease severity, and healthcare utilization: The NHLBI-sponsored Women's Ischemia Syndrome Evaluation

BACKGROUND Anxiety is common among patients presenting with suspected coronary artery disease (CAD). In a sample of women with signs and symptoms of ischemia, we examined three anxiety markers as predictors of CAD endpoints including: 1) cardiac symptom indicators; 2) angiographic CAD severity; and 3) healthcare utilization (cardiac hospitalizations and 5-year cardiovascular [CVD] healthcare costs). METHODS Participants completed a baseline protocol including coronary angiogram, cardiac symptoms, psychosocial measures and a median 5.9-year follow-up to track hospitalizations. We calculated CVD costs based on cardiac hospitalizations, treatment visits, and CVD medications. Anxiety measures included anxiolytic medication use, Spielberger Trait Anxiety Inventory (STAI) scores, and anxiety disorder treatment history. RESULTS The sample numbered 514 women with anxiety measure data and covariates (mean age=57.5 [11.1]). One in five (20.4%) women reported using anxiolytic agents. Anxiety correlated with cardiac symptom indicators (anxiolytic use with nighttime angina and nitroglycerine use; STAI scores and anxiety disorder treatment history with nighttime angina, shortness of breath, and angina frequency). Anxiety disorder treatment history (but not STAI scores or anxiolytics) predicted less severe CAD. Anxiolytic use (but not STAI scores or anxiety disorder treatment history) predicted hospitalizations for chest pain and coronary catheterization (HRs=2.0, 95% CIs=1.1-4.7). Anxiety measures predicted higher 5-year CVD costs (+9.0-42.7%) irrespective of CAD severity. CONCLUSIONS Among women with signs and symptoms of myocardial ischemia, anxiety measures predict cardiac endpoints ranging from cardiac symptom severity to healthcare utilization. Based on these findings, anxiety may warrant greater consideration among women with suspected CAD.

Depression, dietary habits, and cardiovascular events among women with suspected myocardial ischemia.

BACKGROUND Dietary habits and depression are associated with cardiovascular disease risk. Patients with depression often report poor eating habits, and dietary factors may help explain commonly observed associations between depression and cardiovascular disease. METHODS From 1996 to 2000, 936 women were enrolled in the Womens Ischemia Syndrome Evaluation at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (median follow-up, 5.9 years) for adverse outcomes (cardiovascular disease death, heart failure, myocardial infarction, stroke). Participants completed a protocol including coronary angiography (coronary artery disease severity) and depression assessments (Beck Depression Inventory scores, antidepressant use, and depression treatment history). A subset of 201 women (mean age, 58.5 years; standard deviation, 11.4) further completed the Food Frequency Questionnaire for Adults (1998 Block). We extracted daily fiber intake and daily servings of fruit and vegetables as measures of dietary habits. RESULTS In separate Cox regression models adjusted for age, smoking, and coronary artery disease severity, Beck Depression Inventory scores (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.10), antidepressant use (HR, 2.4; 95% CI, 1.01-5.9), and a history of treatment for depression (HR, 2.4; 95% CI, 1.1-5.3) were adversely associated with time to cardiovascular disease outcomes. Fiber intake (HR, 0.87; 95% CI, 0.78-0.97) and fruit and vegetable consumption (HR, 0.36; 95% CI, 0.19-0.70) were associated with a decreased time to cardiovascular disease event risk. In models including dietary habits and depression, fiber intake and fruit and vegetable consumption remained associated with time to cardiovascular disease outcomes, whereas depression relationships were reduced by 10% to 20% and nonsignificant. CONCLUSIONS Among women with suspected myocardial ischemia, we observed consistent relationships among depression, dietary habits, and time to cardiovascular disease events. Dietary habits partly explained these relationships. These results suggest that dietary habits should be included in future efforts to identify mechanisms linking depression to cardiovascular disease.

Ex vivo cardiovascular magnetic resonance measurements of right and left ventricular mass compared with direct mass measurement in excised hearts after transplantation: a first human SSFP comparison

BackgroundCMR is considered the `gold standard’ for non-invasive LV and RV mass quantitation. This information is solely based on gradient-recalled echo (GRE) sequences while contrast dependent on intrinsic T1/T2 characteristics potentially offers superior image contrast between blood and myocardium. This study aims, for the first time in humans, to validate the SSFP approach using explanted hearts obtained from heart transplant recipients. Our objective is establish the correlation between and to validate steady-state free precession (SSFP) derived LV and RV mass vs. autopsy mass of hearts from cardiac transplants patients.MethodsOver three-years, 58 explanted cardiomyopathy hearts were obtained immediately upon orthotopic heart transplantation from the OR. They were quickly cleaned, prepared and suspended in a saline-filled container and scanned ex vivo via SSFP-SA slices to define LV/RV mass. Using an automatic thresholding program, segmentation was achieved in combination with manual trimming (ATMT) of extraneous tissue incorporating 3D cardiac modeling performed by independent and blinded readers. The explanted hearts were then dissected with the ventricles surgically separated at the interventricular septum. Weights of the total heart not excluding papillary and trabecular myocardium, LV and RV were measured via high-fidelity scale. Linear regression and Bland-Altman plots were used to analyze the data. The intra-class correlation coefficient was used to assess intra-observer reliability.ResultsOf the total of 58 explanted hearts, 3 (6%) were excluded due to poor image quality leaving 55 patients (94%) for the final analysis. Significant positive correlations were found between total 3D CMR mass (450 ± 111 g) and total pathology mass (445 ± 116 g; r = 0.99, p < 0.001) as well as 3D CMR measured LV mass (301 ± 93 g) and the pathology measured LV mass (313 ± 96 g; r = 0.95, p < 0.001). Strong positive correlations were demonstrated between the 3D CMR measured RV mass (149 ± 46 g) and the pathology measured RV mass (128 ± 40 g; r = 0.76, p < 0.001). The mean bias between 3D-CMR and pathology measures for total mass, LV mass and RV mass were: 3.0 g, -16 g and 19 g, respectively.ConclusionsSSFP-CMR accurately determines total myocardial, LV and RV mass as compared to pathology weighed explanted hearts despite variable surgical removal of instrumentation (left and right ventricular assist devices, AICD and often apical core removals). Thus, this becomes the first-ever human CMR confirmation for SSFP now validating the distinction of `gold standard’.

Migraine Headache and Long Term Cardiovascular Outcomes: An extended follow-up of the Women's Ischemia Syndrome Evaluation.

BACKGROUND The association between migraine headache and cardiovascular events has been inconsistent. This study determines the long-term risk of cardiovascular events among women with and without a history of migraine headache who were under evaluation for suspected myocardial ischemia in the Womens Ischemia Syndrome Evaluation (WISE). METHODS The WISE is a National Heart, Lung and Blood Institute-sponsored prospective, multicenter study that aims to improve myocardial ischemia evaluation in women. A total of 936 women presenting with symptoms of myocardial ischemia underwent structured data collection and coronary angiography. Information pertaining to migraine headache was available in 917 women. All-cause mortality data were available on all women for a median of 9.5 years, and nonfatal cardiovascular event data were available on 888 women for a median of 6.5 years. RESULTS A total of 224 (24.4%) women reported a history of migraine headache. Compared with women who did not report a history of migraine headache, women with a history of migraine headache had an increased adjusted risk of cardiovascular event (cardiovascular death, nonfatal myocardial infarction, heart failure, or stroke) (hazard ratio 1.83; 95% confidence interval, 1.22-2.75) at a median follow-up of 6.5 years. This result was driven mainly by a twofold increase in the risk of stroke (hazard ratio 2.33; 95% confidence interval, 1.16-4.68). CONCLUSION Among women being evaluated for ischemic heart disease, those reporting a history of migraine headache had increased risk of future cardiovascular events on long-term follow-up. This risk was primarily driven by a more-than twofold increase in the risk of stroke.

Ten-Year Mortality in the WISE Study (Women’s Ischemia Syndrome Evaluation)

Background— The WISE study (Women’s Ischemia Syndrome Evaluation) was a prospective cohort study of 936 clinically stable symptomatic women who underwent coronary angiography to evaluate symptoms and signs of ischemia. Long-term mortality data for such women are limited. Methods and Results— Obstructive coronary artery disease (CAD) was defined as ≥50% stenosis on angiography by core laboratory. We conducted a National Death Index search to assess the mortality of women who were alive at their final WISE contact date. Death certificates were obtained. All deaths were adjudicated as cardiovascular or noncardiovascular by a panel of WISE cardiologists masked to angiographic data. Multivariate Cox proportional hazards regression was used to identify significant independent predictors of mortality. At baseline, mean age was 58±12 years; 176 (19%) were non-white, primarily black; 25% had a history of diabetes mellitus, 59% hypertension, 55% dyslipidemia, and 59% had a body mass index ≥30. During a median follow-up of 9.5 years (range, 0.2–11.5 years), a total of 184 (20%) died. Of these, 115 (62%) were cardiovascular deaths; 31% of all cardiovascular deaths occurred in women without obstructive CAD (<50% stenosis). Independent predictors of mortality were obstructive CAD, age, baseline systolic blood pressure, history of diabetes mellitus, history of smoking, elevated triglycerides, and estimated glomerular filtration rate. Conclusions— Among women referred for coronary angiography for signs and symptoms of ischemia, 1 in 5 died from predominantly cardiac pathogeneses within 9 years of angiographic evaluation. A majority of the factors contributing to the risk of death seem to be modifiable by existing therapies. Of note, 1 in 3 of the deaths in this cohort occurred in women without obstructive CAD, a condition often considered benign and without guideline-recommended treatments. Clinical trials are needed to provide treatment guidance for the group without obstructive CAD.

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study.

Background Sudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Womens Ischemia Syndrome Evaluation) study. Methods and Results Overall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non‐SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person‐hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P<0.0001). However, the proportion of SCD was similar across CAD severity: 40%, 58%, and 38% for no, minimal, and obstructive CAD subgroups, respectively (P value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (P=0.018) and longer corrected QT interval (P=0.023) were independent SCD predictors in the entire cohort. Corrected QT interval was an independent predictor of SCD in women without obstructive CAD (P=0.033). Conclusions SCD contributes substantially to mortality in women with and without obstructive CAD. Corrected QT interval is the single independent SCD risk factor in women without obstructive CAD. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.

Does the presence of Q waves on the EKG accurately predict prior myocardial infarction when compared to cardiac magnetic resonance using late gadolinium enhancement? A cross-population study of noninfarct vs infarct patients

BACKGROUND We hypothesize that infarct detection by electrocardiogram (EKG) is inaccurate as compared with detection by magnetic resonance imaging and is potentially independent of infarct vs noninfarct status. This might have implications for societies in which initial cardiovascular testing is uniformly EKG. OBJECTIVE This study aimed to relate EKG-defined scar to cardiovascular magnetic resonance imaging (CMR)-defined scar independent of the underlying myocardial pathology. METHODS A total of 235 consecutive patients who underwent CMR-late gadolinium enhancement (LGE) with simultaneous EKG were screened for Q waves and compared with patients with a positive LGE pattern. The patients were divided into 3 groups: (1) patients with a positive infarct LGE pattern (LGE+/+; herein defined as LGE+), (2) patients with a noninfarct LGE pattern (LGE+/-), and (3) patients with a negative LGE pattern (LGE-). RESULTS While 139 of 235 patients (59%) were either LGE+ or LGE+/-, pathological Q waves were present in only 74 of 235 patients (31%). However, of these LGE+ or LGE+/- patients, only 76 (32%) had an infarct LGE pattern representing little overlap between the presence of LGE+ and Q waves. EKG sensitivity and specificity to detect infarct: 66% and 85%, respectively. However, of 24 of 74 patients (32%) with Q waves on the EKG, 66% were LGE+/- and 34% were LGE-. Importantly, 3-dimensional volume of myocardial scar was far more predictive of a Q wave than of scar transmurality. CONCLUSION EKG-defined scar, while ubiquitous for an infarct, has low sensitivity than CMR-LGE-defined scar. Unexpectedly, a significant number of pathological Q waves had absent infarct etiology, indicating high false positivity. Similarly, underrecognition of bona fide myocardial infarction frequently occurs, while 3-dimensional CMR volume of myocardial scar is far more predictive of a Q wave than of scar transmurality. This suggests that the well-regarded EKG may be a disservice when applied on a population basis, leading to inappropriate over or under downstream testing with wide socioeconomic implications.