Alessandra Brofferio

Novel variant of dual left anterior descending coronary artery

A 29-year-old African American man presented with atypical chest pain. Coronary computed tomographic angiography (64-slice) showed a previously not described variant of dual (duplicated) left anterior descending artery (LAD). Duplication of LAD is a rare anomaly and has been categorized into 4 angiographic subtypes based on the origin, course, and termination of the short and long LAD. Our case is unique in that, unlike previous subtypes, the short LAD originates independently from the left coronary sinus and that the long LAD arises from the right coronary sinus and has an intramyocardial course before reaching the distal interventricular groove. It can be, thus, considered a new variant of dual LAD (type V).

Cross-sectional multiplane transesophageal echocardiographic measurements: comparison with standard transthoracic values obtained in the same setting.

Background: Several algorithms developed for cost‐effective use of transesophageal echocardiography (TEE) propose elimination of “screening” transthoracic echocardiographic (TTE) studies. Cross‐sectional measurements obtained by TTE (left atrial diameter [LAD], left ventricular internal dimensions in diastole and systole [LVIDd, LVIDs], septal and posterior wall thickness in diastole [VSTd, PWTd], LV end‐diastolic and end‐systolic volumes [LVEDV and LVESV], and LV ejection fraction [LVEF]) have not been standardized for TEE. Methods: Forty‐six patients (age 27 to 85 years, 60 ± 13 years, 25 [54%] women) underwent TEE and TTE studies. TTE was performed while the TEE probe was in place and the patient was still sedated. Standard TTE measurements were compared with corresponding TEE values obtained from mid‐esophageal and transgastric views. Results: Standard TTE measurements compared favorably with those obtained by TEE at the mid‐esophageal three‐chamber view for LAD (3.9 ± 0.6 cm vs 4.0 ± 0.7 cm, P = NS) and at the transgastric long‐axis view for LVIDd (4.6 ± 0.8 cm vs 4.7 ± 0.8 cm, P = NS), LVIDs (3.1 ± 0.9 cm vs 3.1 ± 0.9 cm, P = NS), and VSTd (0.95 ± 0.18 cm vs 0.98 ± 0.19 cm, P = NS). Biplane TTE and TEE measurements of LVEDV (106 ± 35 ml vs 112 ± 38 ml, P = NS), LVESV (37 ± 23 ml vs 37 ± 25 ml, P = NS), and LVEF (67 ± 14% vs 69 ± 14%, P = NS) also correlated closely. The negative predictive values of TEE measurements for excluding abnormal LAD, LVIDd, VSTd, PWTd, and LVEF as defined by TTE were 83%, 94%, 95%, 97%, and 97%, respectively. Conclusion: Cross‐sectional TEE measurements as obtained in this study are equivalent to standard TTE dimensions and provide reliable information that may facilitate interpretation of TEE studies in the absence of TTE information.

Value of Quantitative Analysis of Mitral Regurgitation Jet Eccentricity by Color Flow Doppler for Identification of Flail Leaflet

Early surgical intervention improves the outcome of patients with mitral regurgitation (MR) secondary to flail leaflet. Current criteria for the diagnosis of flail leaflet require a detailed definition of mitral valve anatomy, which is often challenging by transthoracic echocardiography (TTE) and, occasionally, even by transesophageal echocardiography (TEE). We studied 57 patients (mean age 63 +/- 15 years) with anatomically confirmed flail mitral leaflet and a control group of 57 patients (mean age 68 +/-14 years) with at least moderate MR but no flail leaflet. In patients with flail mitral leaflet, the mean angle formed by the axis of the MR jet and the plane of the mitral annulus was 33 +/- 11 degrees and 29 +/- 16 degrees when measured with TTE and TEE, respectively. In controls the mean angle was 66 +/- 16 degrees and 66 +/- 17 degrees by TTE and TEE, respectively (p <0.0001). Based on receiver- operating characteristic analysis, the optimal cutoff jet angle value for diagnosing flail mitral leaflet was 45 degrees with TTE (sensitivity 88%, specificity 88%), and 47 degrees by TEE (sensitivity 88%, specificity 88%). MR jet angles < or =45 degrees were also correctly identified by visual assessment of TTE images in >90% of cases, with good interobserver agreement (k = 0.76). Thus, quantitative analysis of MR jet eccentricity by color flow Doppler is highly sensitive and specific for diagnosing flail mitral leaflet.

Effect of early administration of atropine on paradoxic sinus deceleration during dobutamine stress echocardiography

Dobutamine stress echocardiography (DSE) is a well-established, safe, and reliable technique for diagnosis of coronary artery disease. The generally accepted protocol for DSE involves infusion of increasing doses of dobutamine from 5 to 40 g/kg/min at 3-minute intervals. In about 1/3 of patients, however, target heart rate cannot be achieved by the administration of dobutamine alone. Failure to achieve an adequate heart rate during DSE is attributed to the use of -adrenergic blocking agents, chronotropic incompetence, or paradoxic sinus deceleration (PSD). PSD is characterized by an initial increase followed by a significant decrease in heart rate during incremental doses of dobutamine. This is believed to result from activation of the cardioinhibitory reflex (Bezold-Jarisch reflex) through left ventricular sensory receptors. Although suggested by some, it is unclear whether left ventricular inferoposterior wall ischemia is the trigger for PSD. In the present study, we sought to identify the characteristics of patients with PSD during DSE and to determine whether early administration of atropine could prevent its development. • • • The study population consisted of 114 consecutive patients (age 36 to 91 years [66 12]; 66 women [58%]) with suspected coronary artery disease who were referred for DSE between March and June 2000. Patients were prospectively randomized into 2 protocols. Group A (n 55) underwent standard DSE protocol, consisting of incremental doses of dobutamine from 5 to 40 g/kg/min at 3-minute intervals, and if needed, up to 1 mg of atropine (0.25 mg doses at 2-minute intervals) at the completion of the 40 g/kg/min dose of dobutamine. A 3-minute infusion of dobutamine at 50 g/kg/min was given if necessary at peak (n 2). Patients in group B (n 59) underwent the same protocol except for administration of atropine at completion of the 10 g/kg/min dose of dobutamine with the aim to increase heart rate by 25% before advancing to the next dose of dobutamine. Atropine was not administered if the patient had a specific contraindication. End points for DSE termination were: (1) attainment of target heart rate, (2) completion of stress protocol, (3) echocardiographic evidence of ischemia, or (4) development of significant arrhythmia, hypertension, hypotension, or intolerable symptoms. A standard echocardiographic image acquisition protocol was used and heart rate was recorded from 12-lead electrocardiograms performed at 1-minute intervals. DSE was considered positive for ischemia if any worsening in left ventricular wall motion developed during the test except for a change from akinesia to dyskinesia. PSD was defined as a reduction in heart rate of 5 beats/min lasting for 3 minutes at dobutamine infusion rates of 10 g/kg/min. Data are presented as mean SD and numbers and percentages. Differences between continuous variables were assessed with the unpaired Student’s t test. Chi-square or Fisher’s exact test compared proportions. No statistically significant differences were noted between the 2 groups with regard to age, sex, baseline heart rate, blood pressure, and left ventricular ejection fraction, as well as risk factors for coronary artery disease (Table 1). Similarly, the number of patients who were on -adrenergic blocking agents was not significantly different in the 2 groups (28 [52%] vs 35 [59%], p NS) (Table 1). An equal proportion of the patients in the 2 groups (73%) reached target heart rate ( 85% predicted maximum heart rate for age). In addition, DSE was terminated in 7 patients (13%) in group A and 6 patients (10%) in group B due to myocardial ischemia (p NS). Coronary angiography was performed within 1 month of DSE in 9 of these 13 patients (5 in group A and 4 in group B) and showed significant coronary artery disease ( 50% luminal narrowing in 1 major epicardial coronary artery) in all patients. Safety considerations were the reasons for termination of DSE in 6 patients (11%) in group A and 2 patients (3%) in group B (p NS). The remaining 2 patients (3%) in group A and 8 patients (14%) in group B did not reach target heart rate despite maximal doses of dobutamine and atropine (if not contraindicated) (p NS). Five of the 8 patients in group B who did not reach target heart rate were taking -adrenergic blocking agents, From the Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, New York. Dr. Shirani’s address is: Jack D. Weiler Hospital of the Albert Einstein College of Medicine, Division of Cardiology, 1825 Eastchester Road, Bronx, New York 10461-2373. E-mail: jshirani@montefiore.org. Manuscript received August 6, 2001; revised manuscript received and accepted October 31, 2001.

Impact of β1- and β2-Adrenergic Receptor Gene Single Nucleotide Polymorphisms on Heart Rate Response to Metoprolol Prior to Coronary Computed Tomographic Angiography

A slow, steady heart rate (HR) is necessary for optimal image quality during coronary computed tomographic angiography. Beta blockers are often used, but the goal HR is not achieved in some patients. The aim of this study was to examine the influence of single-nucleotide polymorphisms (SNPs) of the β(1) (codons 49 and 389) and β(2) (codons 16, 27, and 164) adrenergic receptor (AR) genes on HR response to metoprolol in 200 adults (mean age 56 ± 11 years) referred for coronary computed tomographic angiography (using a 64-slice scanner). Oral and intravenous (IV) metoprolol was given to achieve a goal HR of <60 beats/min. Overall, 37 patients (18.5%) did not reach the goal HR despite the administration of oral (181 ± 116 mg) and IV (4.2 ± 9.4 mg) metoprolol. Patients with the β(1)-AR Ser49Gly or Gly49Gly genotype (n = 49) more often failed to reach an optimal HR compared to those with the Ser49Ser genotype (n = 151) (29% vs 15%, p = 0.04), despite receiving higher doses of oral (210 ± 115 vs 172 ± 115 mg, p = 0.048) and IV (7 ± 13 vs 3 ± 8 mg, p = 0.02) metoprolol. Similarly, patients with the β(1)-AR Gly389Gly genotype (n = 11) more often failed to reach an optimal HR compared to those with the Arg389Arg and Arg389Gly genotypes (n = 189) (45% vs 17%, p = 0.02), despite receiving higher doses of IV (13 ± 15 vs 4 ± 9 mg, p = 0.002) but not oral (162 ± 105 vs 182 ± 117 mg, p = 0.50) metoprolol. Multivariate analysis identified β(1)-AR SNPs at codons 49 and 389 and β(2)-AR SNP at codon 27 as independent predictors of suboptimal HR response. In conclusion, these data indicate that the selected SNPs of β(1)-AR and β(2)-AR genes influence HR response to metoprolol in patients who undergo coronary computed tomographic angiography.

Dobutamine-Induced Myocardial Ischemia and ST-Segment Elevation in Collateral-Dependent Myocardium

In patients with obstructive coronary artery disease, electrocardiographic (ECG) ST-segment elevation (STE) is frequently seen during dobutamine stress echocardiography (DSE) in leads overlying previous transmural left ventricular (LV) myocardial infarction. The mechanism of occasional STE during DSE in LV region with inducible myocardial ischemia and no previous myocardial infarction has not been well delineated. We retrospectively identified 28 adults (age 51 to 83 years [69 ± 8]; 82% men) with STE (>1 mm at ≥80 ms after J point in ≥2 contiguous leads without pathologic Q waves) and inducible myocardial ischemia in the same territory during DSE. STE occurred in inferior (n = 16), inferolateral (n = 8), anterior (n = 1), lateral (n = 2), or anterolateral (n = 1) leads and was associated with ischemic symptoms in 17 patients (61%). Inducible LV wall motion abnormality developed in LV segments corresponding to ECG STE in all patients. Coronary arteriography (within 1 week of the index DSE) showed severe luminal narrowing in the major epicardial coronary artery supplying the region with DSE STE and ischemia (90% to 99% in 9 patients [32%] and 100% in 19 patients [68%]). The ischemic region was supplied by ipsilateral (n = 4 [14%]), contralateral (n = 21 [75%]), or both ipsilateral and contralateral (n = 3 [11%]) collateral branches. In conclusion, dobutamine-induced ECG STE in LV segments with normal baseline wall motion is a highly reliable marker of viable collateral-dependent myocardium.

Relation of baseline forearm vasodilator reserve to vascular endothelial response to estrogen replacement therapy in healthy postmenopausal women

E replacement therapy (ERT) may be protective against cardiovascular disease in postmenopausal women without established coronary heart disease, possibly by improving endothelial-dependent arterial dilation (EDAD). However, vascular endothelial function as evaluated by flow-mediated dilation (FMD) varies considerably among postmenopausal women not receiving hormone replacement therapy, and the effects of ERT are inconsistent in this patient population. Whether variability in baseline vascular endothelial function is in part responsible for the inconsistent response to ERT in postmenopausal women is currently unknown. Accordingly, the present study was undertaken to evaluate whether baseline FMD affects the vascular endothelial response to physiologic ERT in healthy postmenopausal women. • • • Seventeen women (age 49 to 68 years; range 56 1), postmenopausal for 2 years, were prospectively studied. Exclusion criteria were use of hormone replacement therapy within 3 months of enrollment, body mass index 32 kg/m, or history of coronary artery disease, congestive heart failure, diabetes, hypertension, stroke, breast or endometrial cancer, deep vein thrombosis, renal failure, or use of lipid-lowering medications. Baseline clinical, laboratory, and echocardiographic findings are listed in Table 1. The Institutional Review Board approved the study and all participants signed informed consent. Laboratory tests and ultrasound examinations were performed at baseline and at the end of a 6-week treatment period with estrogen. Estrogen preparations included transdermal estradiol 0.1 mg (13 of 17 women, 76%) or oral conjugated equine estrogen (Premarin, Wyeth-Ayerst, Philadelphia, Pennsylvania) 0.625 mg/day (4 of 17 women, 24%). The left brachial artery (BA) was imaged using a 12-MHz linear array transducer as previously reported. Reactive hyperemia was produced following release of upper arm cuff occlusion at 50 mm Hg above systolic blood pressure for 5 minutes. After cuff release, pulsewave Doppler was performed immediately and blood flow velocity was measured as early as possible within the initial 30 seconds as an average of 3 consecutive cardiac cycles. Subsequent 2-dimensional and M-mode imaging of the artery for measurement of diameter were performed between 30 and 90 seconds after cuff release. BA systolic blood flow was calculated as: (BA diameter/2) flow VTI , where VTI is the velocity time integral of the Doppler spectral signal. BA FMD was calculated as: (100 [BA diameter postcuff release BA diameter pre cuff release]/BA diameter precuff release) . The degree of reactive hyperemia was calculated as: (100 [BA flow postcuff release BA flow precuff release]/BA flow precuff release) . All data were recorded on super-VHS videotape and selected frames stored on optical disk. Data are expressed as mean SEM, numbers or percentages. Continuous variables were compared using a 2-tailed Student’s t test. A 2-tailed bivariate Pearson’s correlation coefficient was used to assess the relation of baseline FMD to its change following estrogen therapy. A p value of 0.05 was considered significant. Baseline BA diameter increased from 2.88 0.01 to 3.09 0.01 mm after reactive hyperemia, corresponding to a FMD of 7.6 1.4% (range 0% to 17.2%). Following ERT, BA diameter increased from 3.01 0.01 to 3.28 0.01 mm after reactive hyperemia, corresponding to a FMD of 9.2 0.9% (range 2.0% to 12.9%) (Figure 1). Both resting and posthyperemic BA diameters were significantly larger on ERT compared with pretreatment values. However, FMD did not increase significantly with ERT. Baseline BA flow VTI increased from 18 1 to 35 3 cm following reactive hyperemia, corresponding to resting and posthyperemic BA systolic blood flows of 1.14 0.08 and 2.68 0.24 ml/cycle (p 0.001). Following ERT, BA VTI increased from 17 1 to 45 4 cm following reactive hyperemia (Figure 2), corresponding to resting and posthyperemic BA systolic blood flows of 1.17 0.09 and 3.89 0.36 ml/cycle (p 0.001). Thus, resting BA VTI and systolic blood flow were similar before and after ERT. However, posthyperemic BA VTI and systolic blood flow increased significantly following ERT (p 0.001 for both). Reactive hyperemia increased from the baseline value after ERT (162 35% to 243 29%, p 0.05). A strong negative correlation was found between baseline BA FMD and its change from baseline following ERT (r 0.83, p 0.0001). There was no significant correlation between the change in FMD following From the Divisions of Cardiology and Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York. Dr. Ilercil’s address is: Division of Cardiology, The Jack D. Weiler Hospital of the Albert Einstein College of Medicine, 1825 Eastchester Road, Room W1-70, Bronx, New York 10461-2373. E-mail: ailercil@ montefiore.org. Manuscript received October 9, 2001; revised manuscript received and accepted January 24, 2002.