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    Jannet Lewis

    Breast arterial calcification (BAC) is a type of medial artery calcification that can be seen incidentally on mammography. Studies have suggested association of BAC with cardiovascular risk factors, coronary artery disease (CAD), and... more
    Breast arterial calcification (BAC) is a type of medial artery calcification that can be seen incidentally on mammography. Studies have suggested association of BAC with cardiovascular risk factors, coronary artery disease (CAD), and cardiovascular morbidity and mortality. Recently published studies have also suggested a modest correlation of BAC with coronary artery calcium (CAC) scoring. Roughly 40 million mammograms are already performed annually in the United States with overlap in patients that undergo CAD screening via CAC scoring. Thus, identification of cardiovascular risk by demonstrating an association between BAC and CAC may enable an instrumental sex-specific methodology to identify asymptomatic women at risk for CAD. The purpose of this article is to review the current state of the literature for BAC and its association with CAC, to review contemporary breast cancer screening guidelines, and to discuss the clinical implications of these findings.
    This report describes a subgroup of 17 patients with hypertrophic cardiomyopathy and an unusual and distinctive pattern of left ventricular hypertrophy characterized on echocardiography by marked thickening of the posterior left... more
    This report describes a subgroup of 17 patients with hypertrophic cardiomyopathy and an unusual and distinctive pattern of left ventricular hypertrophy characterized on echocardiography by marked thickening of the posterior left ventricular free wall and virtually normal or only modestly increased ventricular septal thickness. This distribution of hypertrophy often created a distinctive pattern of "inverted" asymmetry of the posterior wall relative to the septum. The thickness of the posterior wall was 20 to 42 mm (mean 25), while that of the basal ventricular septum was only 12 to 24 mm (mean 17). The left ventricular outflow tract was narrowed because of anterior displacement of the mitral valve within the small left ventricular cavity. Systolic anterior motion of the mitral valve was present in 16 of the 17 patients. The patients ranged in age from 13 to 54 years (mean 31) at most recent evaluation; most (11 of 17, 65%) were severely symptomatic and had experienced important symptoms early in life (before age 40). The condition of only 4 of these 11 patients improved with medical therapy over an average follow-up period of 9 years; however, 6 of the 7 patients who had unsuccessful medical treatment and underwent operation with mitral valve replacement (5 patients) or ventricular septal myotomy-myectomy (1 patient) experienced symptomatic benefit from surgery. The subgroup of patients described in this report underscores the morphologic and clinical diversity that exists within the overall disease spectrum of hypertrophic cardiomyopathy. Characteristically, the patients were young, severely symptomatic and demonstrated evidence of outflow obstruction and an "inverted" asymmetric pattern of posterior free wall left ventricular hypertrophy. (ABSTRACT TRUNCATED AT 250 WORDS)
    To determine the pharmacodynamic parameters of dobutamine during dobutamine stress echocardiography (DSE) and to determine how beta-blocker withdrawal the evening before DSE affects responses to dobutamine during DSE. Retrospective... more
    To determine the pharmacodynamic parameters of dobutamine during dobutamine stress echocardiography (DSE) and to determine how beta-blocker withdrawal the evening before DSE affects responses to dobutamine during DSE. Retrospective analysis. University medical center. One hundred thirty-six women who had chest pain or other symptoms suggestive of myocardial ischemia and were considered to have a clinical indication for coronary angiography Patients underwent DSE with dobutamine dosages titrated from 5 to 40 microg/kg/minute. The infusion was terminated if the patient reached target heart rate or symptoms developed. Those taking beta-blockers withheld their doses the evening before DSE. Traditional pharmacodynamic modeling revealed a wide range in responses to dobutamine. Data for 62% of patients not taking beta-blockers were described by the Emax (maximum heart rate response to dobutamine) model, whereas data for only 39% of patients taking beta-blockers were best described by this model (p = 0.01). Patients taking beta-blockers also had a smaller mean increment in left ventricular ejection fraction (10.8% +/- 4.2% vs 14.1% +/- 9.3%, p < 0.01), a trend toward a higher ED50 (dobutamine dosage rate causing half the maximum heart-rate response; median 16.8 microg/kg/min, p = 0.12) and a lower sigmoidicity factor determining the shape of the curve (median 2.1, p = 0.03). The response to dobutamine exhibits wide interpatient variability, even in the absence of beta-blockade. Nonetheless, in the absence of beta-blockers, in most patients the dobutamine response reaches a plateau by the time the maximum infusion rate (40 microg/kg/min) is reached. Withdrawal of beta-blockers the evening before DSE may be inadequate time for elimination of beta-blocker effect, requiring the addition of atropine to achieve the desired response during DSE.
    Our objective was to determine if β1-adrenergic receptor (β1-AR) and β2-AR gene polymorphisms influence heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) response to dobutamine during dobutamine stress... more
    Our objective was to determine if β1-adrenergic receptor (β1-AR) and β2-AR gene polymorphisms influence heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) response to dobutamine during dobutamine stress echocardiography (DSE). Patients (n=163) undergoing clinically indicated DSE were enrolled. Dobutamine doses were titrated from 5 to 40 μg kg−1 min−1 at 3 min intervals and HR, SBP
    Mitral valve prolapse is a common clinical disorder that affects approximately 3-4% of the adult population. Prolapse occurs more commonly in women and has been associated with a variety of cardiac complications including mitral... more
    Mitral valve prolapse is a common clinical disorder that affects approximately 3-4% of the adult population. Prolapse occurs more commonly in women and has been associated with a variety of cardiac complications including mitral regurgitation, endocarditis, arrhythmias, and sudden death, as well as noncardiac manifestations including stroke. Much of our earlier understanding has been influenced by significant referral biases and lack of controlled studies. Our understanding of mitral prolapse has evolved considerably since the initial descriptions nearly 3 decades ago. This review on the current knowledge regarding diagnosis and management of primary mitral valve prolapse focuses on gender-related issues that influence clinical presentation, prognosis, and therapeutic strategies.
    Coronary artery disease (CAD) is the most common cause of death in women. In general, noninvasive testing in women is less reliable compared with testing in men, and most major clinical trials in CAD have included only a minority of... more
    Coronary artery disease (CAD) is the most common cause of death in women. In general, noninvasive testing in women is less reliable compared with testing in men, and most major clinical trials in CAD have included only a minority of female subjects. The Women's Ischemia Syndrome Evaluation (WISE) Study--sponsored by the National Heart, Lung, and Blood Institute--was initiated to improve diagnostic testing in women. The study consisted of four centers that tested existing methodologies as well as innovative techniques to improve diagnostic testing in women. The WISE study also aimed to clarify physiologic determinants of myocardial ischemia and determine whether angiographically normal coronary arteries are associated with myocardial ischemia. The following discussion provides an overview of the WISE study and reviews the reported and published data from the study.
    Women with obstructive coronary disease appear to be more challenging diagnostically and suffer a more adverse prognosis than men. More than one half of women with symptoms of ischemic heart disease have no obstructive coronary artery... more
    Women with obstructive coronary disease appear to be more challenging diagnostically and suffer a more adverse prognosis than men. More than one half of women with symptoms of ischemic heart disease have no obstructive coronary artery disease at coronary angiography, yet these women frequently have persistent symptom-related disability and consume large amounts of healthcare resources. Prior evidence has been limited regarding effective diagnostic strategies for the assessment of symptomatic women. The current report synthesizes existing evidence on diagnostic testing in women, including research from the ongoing National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In addition to recent published evidence (drawn from much larger cohorts of women) that stress echocardiography and nuclear imaging are similar in their ability to risk-stratify women, the WISE study is exploring new pathophysiological mechanisms of microvascular dysfu...
    Studies with other imaging modalities have demonstrated a relationship between contrast transit and cardiac output (CO) and pulmonary vascular resistance (PVR). We tested the hypothesis that the transit time during contrast... more
    Studies with other imaging modalities have demonstrated a relationship between contrast transit and cardiac output (CO) and pulmonary vascular resistance (PVR). We tested the hypothesis that the transit time during contrast echocardiography could accurately estimate both CO and PVR compared to right heart catheterization (RHC). 27 patients scheduled for RHC had 2D-echocardiogram immediately prior to RHC. 3 ml of DEFINITY contrast followed by a 10 ml saline flush was injected, and a multi-cycle echo clip was acquired from the beginning of injection to opacification of the left ventricle. 2D-echo based calculations of CO and PVR along with the DEFINITY-based transit time calculations were subsequently correlated with the RHC-determined CO and PVR. The transit time from full opacification of the right ventricle to full opacification of the left ventricle inversely correlated with CO (r=-0.61, p<0.001). The transit time from peak opacification of the right ventricle to first appearan...
    Our objective was to determine if beta(1)-adrenergic receptor (beta(1)-AR) and beta(2)-AR gene polymorphisms influence heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) response to dobutamine during... more
    Our objective was to determine if beta(1)-adrenergic receptor (beta(1)-AR) and beta(2)-AR gene polymorphisms influence heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) response to dobutamine during dobutamine stress echocardiography (DSE). Patients (n=163) undergoing clinically indicated DSE were enrolled. Dobutamine doses were titrated from 5 to 40 microg kg(-1) min(-1) at 3 min intervals and HR, SBP and DBP were measured. Genotypes were determined for beta(1)-AR Ser49Gly, beta(1)-AR Arg389Gly, beta(2)-AR Arg16Gly and beta(2)-AR Gln27Glu polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis, pyrosequencing and single primer extension methods. beta(2)-AR Glu27 homozygotes had a greater HR response at the highest dobutamine dose than Gln27 carriers (P=0.002). Beta(2)-AR Gly16 homozygotes had a lower HR response during 5-30 microg kg(-1) min(-1) of the dobutamine infusion protocol compared to Arg16 carriers (P=0.03). Differences in SBP by beta(2)-AR codon 16 genotype and DBP by beta(1)-AR codon 389 genotype were found at baseline and were maintained throughout DSE (P=0.06 and 0.02, respectively). However, the magnitude of SBP and DBP response to dobutamine did not differ significantly by beta(2)-AR codon 16 or beta(1)-AR codon 389 genotypes, respectively. These data suggest that the four selected beta(1)- and beta(2)-AR polymorphisms do not substantially influence the magnitude of hemodynamic response to dobutamine during DSE.
    This report describes a subgroup of 17 patients with hypertrophic cardiomyopathy and an unusual and distinctive pattern of left ventricular hypertrophy characterized on echocardiography by marked thickening of the posterior left... more
    This report describes a subgroup of 17 patients with hypertrophic cardiomyopathy and an unusual and distinctive pattern of left ventricular hypertrophy characterized on echocardiography by marked thickening of the posterior left ventricular free wall and virtually normal or only modestly increased ventricular septal thickness. This distribution of hypertrophy often created a distinctive pattern of "inverted" asymmetry of the posterior wall relative to the septum. The thickness of the posterior wall was 20 to 42 mm (mean 25), while that of the basal ventricular septum was only 12 to 24 mm (mean 17). The left ventricular outflow tract was narrowed because of anterior displacement of the mitral valve within the small left ventricular cavity. Systolic anterior motion of the mitral valve was present in 16 of the 17 patients. The patients ranged in age from 13 to 54 years (mean 31) at most recent evaluation; most (11 of 17, 65%) were severely symptomatic and had experienced important symptoms early in life (before age 40). The condition of only 4 of these 11 patients improved with medical therapy over an average follow-up period of 9 years; however, 6 of the 7 patients who had unsuccessful medical treatment and underwent operation with mitral valve replacement (5 patients) or ventricular septal myotomy-myectomy (1 patient) experienced symptomatic benefit from surgery. The subgroup of patients described in this report underscores the morphologic and clinical diversity that exists within the overall disease spectrum of hypertrophic cardiomyopathy. Characteristically, the patients were young, severely symptomatic and demonstrated evidence of outflow obstruction and an "inverted" asymmetric pattern of posterior free wall left ventricular hypertrophy. (ABSTRACT TRUNCATED AT 250 WORDS)
    ... Sidney Fu, and Ian Toma Timothy McCaffrey, Constantine Tziros, Jannet Lewis, Robert Siegel, Richard Katz, OF THE TCL1A/AKT ANTI-APOPTOTIC PATHWAY CARDIOTOXICITY SUGGESTS A POSSIBLE ROLE OF SUPPRESSION GENOMIC ANALYSIS OF CHEMOTHERAPY... more
    ... Sidney Fu, and Ian Toma Timothy McCaffrey, Constantine Tziros, Jannet Lewis, Robert Siegel, Richard Katz, OF THE TCL1A/AKT ANTI-APOPTOTIC PATHWAY CARDIOTOXICITY SUGGESTS A POSSIBLE ROLE OF SUPPRESSION GENOMIC ANALYSIS OF CHEMOTHERAPY ...
    ... Coll. Cardiol. Lewis Brian Choi, Monica Mukherjee, Cynthia M. Tracy, Richard J. Katz, and Jannet F. ON WEB-ENABLED SMARTPHONE ACQUISITION BY HANDHELD ULTRASOUND AND INTERPRETATION VALIDATION OF MOBILE-TO-MOBILE ECHOCARDIOGRAM ...
    To determine whether left ventricular diastolic abnormalities are an early feature of sickle cell anemia, indexes of diastolic filling were obtained with pulsed Doppler echocardiography in 30 consecutive patients with this disease (mean... more
    To determine whether left ventricular diastolic abnormalities are an early feature of sickle cell anemia, indexes of diastolic filling were obtained with pulsed Doppler echocardiography in 30 consecutive patients with this disease (mean age 29 years; range 19 to 39) who had not experienced symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those in 30 normal control subjects of similar ages. Seventeen (57%) of the 30 patients with sickle cell anemia had evidence of abnormal left ventricular diastolic filling. Six of these 17 patients had a Doppler pattern consistent with "restrictive" filling, characterized by reduced early diastolic deceleration time (less than 110 ms) or an increased rate of decline of early flow velocity (EF slope greater than 7.4 m/s2), or both, as well as decreased late diastolic velocity-time integral (2.6 +/- 0.7 vs. 3.4 +/- 0.8 cm in normal subjects; p less than 0.05). Another 11 patients showed a Doppler waveform consistent with impaired relaxation, characterized by prolonged deceleration time (greater than 166 ms) or reduced EF slope (less than 3.8 m/s2), as well as increased late diastolic velocity-time integral (4.0 +/- 0.5 vs. 3.4 +/- 0.8 cm in normal subjects; p = 0.03). This Doppler echocardiographic analysis demonstrates that left ventricular diastolic filling patterns are altered in patients with sickle cell anemia and that these diastolic abnormalities may be present in the absence of symptoms of heart failure. These abnormal patterns suggest an intrinsic myocardial abnormality in patients with sickle anemia and may prove to be early markers of cardiac disease.
    This report describes a subgroup of 52 elderly patients with obstructive hypertrophic cardiomyopathy in whom certain clinical and morphologic features differed importantly from those of many other patients with this disease. Ages ranged... more
    This report describes a subgroup of 52 elderly patients with obstructive hypertrophic cardiomyopathy in whom certain clinical and morphologic features differed importantly from those of many other patients with this disease. Ages ranged from 60 to 84 years (mean 69) and 45 [87%] were women. Echocardiographic examination showed a relatively small heart, having only modest ventricular septal hypertrophy associated with marked distortion of left ventricular outflow tract morphology. By virtue of selection, left ventricular outflow tract size at end-diastole was substantially reduced, and anterior displacement of the mitral valve within the left ventricular cavity was particularly marked. Sizable deposits of calcium in the region of the mitral anulus, posterior to the mitral valve, appeared to contribute to the outflow tract narrowing. Systolic anterior motion of the mitral valve was severe (with apposition of the mitral valve and ventricular septum) in 32 patients and more moderate in 20. The mechanism by which systolic contact between the mitral valve and septum occurred in most patients appeared to differ from that observed more typically in many other patients with hypertrophic cardiomyopathy; in most elderly study patients, anterior excursion of the mitral valve leaflets was relatively restricted, and systolic apposition between the mitral valve and septum resulted from a combination of anterior motion of the mitral valve and posterior excursion of the septum. The vast majority (50 of 52) of the patients remained asymptomatic (or only mildly symptomatic) for most of their lives and often did not develop severe and intractable symptoms until the 6th or 7th decade (ages 56 to 81 years; mean 66). Of the 49 patients with at least 1 year follow-up study, only 12 had improvement with pharmacologic therapy; however, 14 of the 18 patients who underwent ventricular septal myotomy-myectomy or mitral valve replacement obtained symptomatic benefit from operation. In conclusion, obstructive hypertrophic cardiomyopathy in many elderly (and predominantly female) patients may assume a distinctive morphologic appearance and a progressive clinical course. This subgroup of patients appears to constitute an important segment of the disease spectrum of hypertrophic cardiomyopathy of cardiac disease in the elderly that previously has not been precisely defined nor fully appreciated.
    The purpose of the present study was to assess the influence of variations in the relative degree of dilation of left and right ventricular chambers on the clinical outcome of patients with dilated cardiomyopathy. Dilated cardiomyopathy,... more
    The purpose of the present study was to assess the influence of variations in the relative degree of dilation of left and right ventricular chambers on the clinical outcome of patients with dilated cardiomyopathy. Dilated cardiomyopathy, a primary myocardial disease characterized by ventricular dilation and systolic dysfunction, is generally associated with a poor prognosis. However, considerable variability has been observed in the clinical course and the morphologic and hemodynamic features in individual patients. We evaluated 67 consecutive patients with dilated cardiomyopathy and without evidence of ischemic or primary valvular heart disease. On the basis of diastolic ventricular chamber area measurements obtained by echocardiography, patients were classified into two groups: 38 patients with a relatively equal degree of left and right ventricular dilation (LV congruent to RV) and 29 patients with predominant and disproportionate dilation of the left ventricle (LV > RV). The 67 patients ranged in age from 19 to 81 years (mean 56); 49 (73%) were male. The two subsets of patients with dilated cardiomyopathy did not differ with regard to age, left ventricular diastolic dimension, wall thickness and mass or ejection fraction. However, patients in the LV congruent to RV group showed more severe mitral and tricuspid regurgitation by Doppler echocardiography than did those in the LV > RV group (p = 0.01 for mitral and 0.004 for tricuspid regurgitation). Over the follow-up period of 2 to 60 months (mean 28), there were 19 deaths. Survival in the LV > RV group was significantly better than in the LV congruent to RV group (p = 0.03). Patients with dilated cardiomyopathy represent a heterogeneous group with regard to both clinical outcome and the relative degree of left and right ventricular chamber dilation. Patients in the LV > RV subset appear to have better overall survival and less severe mitral and tricuspid regurgitation than do patients in the LV congruent to RV subset. Longitudinal studies are needed to determine whether these morphologic subsets in fact represent a continuum within the disease spectrum of dilated cardiomyopathy.
    Pulmonary hypertension (PH) in patients with systemic hypertension and preserved ejection fraction (PEF) has been described. However, the pathophysiology and consequences are not entirely clear. We sought to distinguish the clinical and... more
    Pulmonary hypertension (PH) in patients with systemic hypertension and preserved ejection fraction (PEF) has been described. However, the pathophysiology and consequences are not entirely clear. We sought to distinguish the clinical and anatomic features among hypertensive patients with or without coexistent PH. Echocardiograms and records of hypertensive patients with left ventricular (LV) hypertrophy and PEF from January 2009 to January 2011 were reviewed. We identified 174 patients, including 36 with PH (calculated pulmonary artery systolic pressure [PASP] ≥ 35 mmHg), and 138 with normal pulmonary pressures. Hypertensive patients with PH were older (76 ± 13 vs. 65 ± 13 years, P < 0.0001), more often female (91, 70%), had lower estimated glomerular filtration rate (eGFR) (63 ± 44 vs. 88 ± 48 mL/min, P = 0.002), and higher pro-BNP levels (3141 ± 4253 vs. 1219 ± 1900 pg/mL, P = 0.003). PH patients also had larger left atrial areas (23.7 ± 3.8 vs. 20.8 ± 4.6 cm(2) , P = 0.002), evidence of diastolic dysfunction (i.e., septal E/e' 17.6 ± 8.6 vs. 12.7 ± 4.4, P = 0.0005), and higher calculated peripheral vascular resistance (PVR) (2.3 ± 1.1 vs. 1.6 ± 0.4, P < 0.0001). Both PVR and septal E/e' showed strong linear correlation with PASP (P < 0.0001 and P < 0.0001, respectively). Hypertension in elderly patients is frequently complicated by LV diastolic dysfunction and secondary PH. These hypertensive patients tended to have reduced renal function and higher pro-BNP. Because of the known morbidity and mortality associated with PH, these observations have potentially important implications for target medical therapy.
    ABSTRACT

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