Nathaniel Reichek

The Women’s Ischemia Syndrome Evaluation (WISE) Study: protocol design, methodology and feasibility report ☆

OBJECTIVESnThe Womens Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute-sponsored, four-center study designed to: 1) optimize symptom evaluation and diagnostic testing for ischemic heart disease; 2) explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenoses, and 3) evaluate the influence of reproductive hormones on symptoms and diagnostic test response.nnnBACKGROUNDnAccurate diagnosis of ischemic heart disease in women is a major challenge to physicians, and the role reproductive hormones play in this diagnostic uncertainty is unexplored. Moreover, the significance and pathophysiology of ischemia in the absence of significant epicardial coronary stenoses is unknown.nnnMETHODSnThe WISE common core data include demographic and clinical data, symptom and psychosocial variables, coronary angiographic and ventriculographic data, brachial artery reactivity testing, resting/ambulatory electrocardiographic monitoring and a variety of blood determinations. Site-specific complementary methods include physiologic and functional cardiovascular assessments of myocardial perfusion and metabolism, ventriculography, endothelial vascular function and coronary angiography. Women are followed for at least 1 year to assess clinical events and symptom status.nnnRESULTSnIn Phase I (1996-1997), a pilot phase, 256 women were studied. These data indicate that the WISE protocol is safe and feasible for identifying symptomatic women with and without significant epicardial coronary artery stenoses.nnnCONCLUSIONSnThe WISE study will define contemporary diagnostic testing to evaluate women with suspected ischemic heart disease. Phase II (1997-1999) is ongoing and will study an additional 680 women, for a total WISE enrollment of 936 women. Phase III (2000) will include patient follow-up, data analysis and a National Institutes of Health WISE workshop.

Early Contrast-Enhanced MRI Predicts Late Functional Recovery After Reperfused Myocardial Infarction

BACKGROUNDnWe have observed 3 abnormal patterns on contrast-enhanced MRI early after reperfused myocardial infarction (MI): (1) absence of normal first-pass signal enhancement (HYPO), (2) normal first pass signal followed by hyperenhanced signal on delayed images (HYPER), or (3) both absence of normal first-pass enhancement and delayed hyperenhancement (COMB). This study examines the association between these patterns in the first week after MI and late recovery of myocardial contractile function by use of magnetic resonance myocardial tissue tagging.nnnMETHODS AND RESULTSnSeventeen patients (14 men) with a mean age of 53+/-12 years were studied after a reperfused first MI. Contrast-enhanced images were acquired immediately after bolus administration of gadolinium and 7+/-2 minutes later. Tagged images were acquired at weeks 1 and 7. Circumferential segment shortening (%S) was measured in regions displaying HYPER, COMB, or HYPO contrast patterns and in remote regions (REMOTE) at weeks 1 and 7. At week 1, %S was depressed in HYPER, COMB, and HYPO (9+/-8%, 7+/-6%, and 5+/-4%, respectively) and were less than REMOTE (18+/-6%, P<0.003). However, in HYPER, %S improved at week 7 from 9+/-8% to 18+/-5% (P<0.001 versus week 1). In contrast, HYPO did not improve significantly (5+/-4% to 6+/-3%, P=NS) and COMB tended to improve 7+/-6% to 11+/-6% (P=0.06).nnnCONCLUSIONSnHYPER has partially reversible dysfunction and represents predominantly viable myocardium. COMB shows borderline improvement and likely contains an admixture of viable and necrotic myocardium. HYPO shows little functional improvement at 7 weeks, presumably because of irreversible myocardial damage.

Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory).

The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Womens Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant ( > 50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in < 10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p < 0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk.

Age-associated changes in regional aortic pulse wave velocity ☆

OBJECTIVESnThis study was designed to determine noninvasively the age-associated changes in regional mechanical properties in normals using phase-contrast magnetic resonance imaging (PCMRI).nnnBACKGROUNDnIt has been well documented that there is a progressive increase in aortic pulse wave velocity (PWV) with age. Previously, PWV has been measured at a single aortic location, or has compared arterial waves between carotid and femoral points to determine PWV.nnnMETHODSnApplanation tonometry (TONO) and in-plane PCMR was performed in 24 volunteers (12 men) ranging in age from 21 to 72 years old. The PCMRI PWV was measured in three aortic segments. As validation, TONO was performed to determine PWV between the carotid and femoral artery.nnnRESULTSnWhen PCMRI PWV was averaged over the three locations, it was not different from TONO (7.9 +/- 2.3 vs. 7.6 +/- 2.4 m/s, respectively). When the volunteers were divided into groups of < 55 and > or =55 years old, the younger group showed similar PWV at each aortic location. However, the older group displayed significantly increased PWV in the region spanning the ascending and proximal descending aorta compared with the mid-thoracic or abdominal segments (10.6 +/- 2.5 m/s, 9.2 +/- 2.8 m/s, and 7.1 +/- 1.7 m/s, respectively, p < 0.001, analysis of variance).nnnCONCLUSIONSnIn-plane PCMRI permits determination of PWV in multiple aortic locations in a single acquisition. Progressive fragmentation of elastic fibers and alterations in the regulation of vascular tone may result in an age-related, regional increase in PWV primarily affecting the proximal aorta.

Characterization of Signal Properties in Atherosclerotic Plaque Components by Intravascular MRI

Magnetic resonance imaging (MRI) is capable of distinguishing between atherosclerotic plaque components solely on the basis of biochemical differences. However, to date, the majority of plaque characterization has been performed by using high-field strength units or special coils, which are not clinically applicable. Thus, the purpose of the present study was to evaluate MRI properties in histologically verified plaque components in excised human carotid endarterectomy specimens with the use of a 5F catheter-based imaging coil, standard acquisition software, and a clinical scanner operating at 0.5 T. Human carotid endarterectomy specimens from 17 patients were imaged at 37 degrees C by use of an opposed solenoid intravascular radiofrequency coil integrated into a 5F double-lumen catheter interfaced to a 0.5-T General Electric interventional scanner. Cross-sectional intravascular MRI (156x250 microm in-plane resolution) that used different imaging parameters permitted the calculation of absolute T1and T2, the magnetization transfer contrast ratio, the magnitude of regional signal loss associated with an inversion recovery sequence (inversion ratio), and regional signal loss in gradient echo (gradient echo-to-spin echo ratio) in plaque components. Histological staining included hematoxylin and eosin, Massons trichrome, Kossa, oil red O, and Gomoris iron stain. X-ray micrographs were also used to identify regions of calcium. Seven plaque components were evaluated: fibrous cap, smooth muscle cells, organizing thrombus, fresh thrombus, lipid, edema, and calcium. The magnetization transfer contrast ratio was significantly less in the fibrous cap (0.62+/-13) than in all other components (P<0.05) The inversion ratio was greater in lipid (0.91+/-0.09) than all other components (P<0.05). Calcium was best distinguished by using the gradient echo-to-spin echo ratio, which was lower in calcium (0.36+/-0.2) than in all plaque components, except for the organizing thrombus (P<0.04). Absolute T1 (range 300+/-140 ms for lipid to 630+/-321 ms for calcium) and T2 (range 40+/-12 ms for fresh thrombus to 59+/-21 ms for smooth muscle cells) were not significantly different between groups. In vitro intravascular MRI with catheter-based coils and standard software permits sufficient spatial resolution to visualize major plaque components. Pulse sequences that take advantage of differences in biochemical structure of individual plaque components show quantitative differences in signal properties between fibrous cap, lipid, and calcium. Therefore, catheter-based imaging coils may have the potential to identify and characterize those intraplaque components associated with plaque stability by use of existing whole-body scanners.

MRI myocardial tagging

MRI myocardial tagging is now a well‐developed method for evaluation of regional myocardial contraction. A series of progressively more refined imaging strategies, combined with advances in analytic strategies have provided a strong armamentarium of methods. Important insights into normal human physiology of left ventricular systolic and diastolic function have been developed using one‐dimensional, two‐dimensional and three‐dimensional analyses of myocardial deformation. In disease states, improved understanding and detection of early alterations in myocardial function in hypertensive heart disease has been possible. In addition, improved understanding of effects of ischemia and infarction on regional function has been possible. Further, after acute myocardial infarction, clearer definition of the natural history of contractile dysfunction in the infarct region and the zone adjacent to the infarct have been possible. Similarly, effects on regional function of a number of important pharmacologic agents used for treatment, such as angiotensin converting enzyme inhibitors, beta blockers and angiotensin receptor blockers have been characterized. In the cardiomyopathies, myocardial tagging has permitted more reliable assessment of heterogeneity of segmental function, especially in hypertrophic cardiomyopathy. Finally, initial applications of myocardial tagging to assessment of right ventricular regional function in hypertrophied hearts with and without major congenital abnormalities have generated advances in understanding of effects of hypertrophy on right ventricular function.J. Magn. Reson. Imaging 1999;10:609–616.

Effect of general anesthesia on the severity of mitral regurgitation by transesophageal echocardiography

The effect of general anesthesia on the severity of mitral regurgitation (MR) was examined in 43 patients with moderate or severe MR who underwent preoperative and intraoperative transesophageal echocardiography. Systolic blood pressure, mean arterial pressure, and left ventricular end-diastolic and end-systolic dimensions were significantly lower during the intraoperative study, reflecting altered loading conditions. The mean color Doppler jet area and mean vena contracta decreased and the mean pulmonary venous flow pattern changed from reversed to blunted, reflecting a significant reduction in the severity of MR. Overall, 22 of the 43 patients (51%) improved at least 1 MR severity grade when assessed under general anesthesia. Thus, intraoperative transesophageal echocardiography may significantly underestimate the severity of MR. A thorough preoperative assessment is preferable when deciding whether to perform mitral valve surgery.

Weight cycling and high-density lipoprotein cholesterol in women: evidence of an adverse effect: A report from the NHLBI-sponsored WISE study☆

OBJECTIVESnWe undertook an analysis of weight cycling, coronary risk factors and angiographic coronary artery disease (CAD) in women.nnnBACKGROUNDnThe effect of weight cycling on cardiovascular mortality and morbidity is controversial, and the impact of weight cycling on cardiovascular risk factors is unclear.nnnMETHODSnThis is a cross-sectional population study of 485 women with coronary risk factors undergoing coronary angiography for evaluation of suspected myocardial ischemia enrolled in the Womens Ischemia Syndrome Evaluation (WISE). Reported lifetime weight cycling-defined as voluntary weight loss of at least 10 lbs at least 3 times--coronary risk factors including core laboratory determined blood lipoproteins and CAD, as determined by a core angiographic laboratory, are the main outcome measures.nnnRESULTSnOverall, 27% of women reported weight cycling--19% cycled 10 to 19 lbs, 6% cycled 20 to 49 lbs, and 2% cycled 50+ lbs. Reported weight cycling was associated with 7% lower high-density lipoprotein cholesterol (HDL-C) levels in women (p = 0.01). The HDL-C effect was directly related to the amount of weight cycled with women who lost > or = 50 lbs/cycle having HDL-C levels 27% lower than noncyclers (p = 0.0025). This finding was independent of other HDL-C modulators, including estrogen status, physical activity level, alcohol intake, body mass index, diabetes, beta-blocker use, cigarette smoking and race. Weight cycling was not associated with an increased prevalence of CAD in this population.nnnCONCLUSIONSnWeight cycling is associated with lower HDL-C in women of a magnitude that is known to be associated with an increased risk of cardiac events as demonstrated in prior clinical trials.

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry.

OBJECTIVESnThis study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation.nnnBACKGROUNDnMagnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo.nnnMETHODSnCircumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites.nnnRESULTSnPaired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001).nnnCONCLUSIONSnMagnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.

Psychosocial Variables Are Associated With Atherosclerosis Risk Factors Among Women With Chest Pain: The WISE Study

Objective We investigated associations between atherosclerosis risk factors (smoking behavior, serum cholesterol, hypertension, body mass index, and functional capacity) and psychological characteristics with suspected linkages to coronary disease (depression, hostility, and anger expression) in an exclusively female cohort. Methods Six hundred eighty-eight middle-aged women with chest pain warranting clinical investigation completed a comprehensive diagnostic protocol that included quantitative coronary angiography to assess coronary artery disease (CAD). Primary analyses controlled for menopausal status, age, and socioeconomic status variables (income and education). Results High depression scores were associated with a nearly three-fold risk of smoking (odds ratio (OR) = 2.8, 95% confidence interval (CI) = 1.4–5.7) after covariate adjustment, and women reporting higher depression symptoms were approximately four times more likely to describe themselves in the lowest category of functional capacity (OR = 3.7, 95% CI = 1.7–7.8). High anger-out scores were associated with a four-fold or greater risk of low high-density lipoprotein cholesterol concentration (<50 mg/dl; OR = 4.0, 95% CI = 1.4–11.1) and high low-density lipoprotein cholesterol concentration (>160 mg/dl; OR = 4.8, 95% CI = 1.5–15.7) and a larger body mass index (OR = 3.5, 95% CI = 1.1–10.8) after covariate adjustment. Conclusions These results demonstrate consistent and clinically relevant relationships between psychosocial factors and atherosclerosis risk factors among women and may aid our understanding of the increased mortality risk among women reporting high levels of psychological distress.