Swaminatha V. Gurudevan

Reproducibility of Proximal Isovelocity Surface Area, Vena Contracta, and Regurgitant Jet Area for Assessment of Mitral Regurgitation Severity

OBJECTIVES The aim of this study was to evaluate the interobserver agreement of proximal isovelocity surface area (PISA) and vena contracta (VC) for differentiating severe from nonsevere mitral regurgitation (MR). BACKGROUND Recommendation for MR evaluation stresses the importance of VC width and effective regurgitant orifice area by PISA measurements. Reliable and accurate assessment of MR is important for clinical decision making regarding corrective surgery. We hypothesize that color Doppler-based quantitative measurements for classifying MR as severe versus nonsevere may be particularly susceptible to interobserver agreement. METHODS The PISA and VC measurements of 16 patients with MR were interpreted by 18 echocardiologists from 11 academic institutions. In addition, we obtained quantitative assessment of MR based on color flow Doppler jet area. RESULTS The overall interobserver agreement for grading MR as severe or nonsevere using qualitative and quantitative parameters was similar and suboptimal: 0.32 (95% confidence interval [CI]: 0.1 to 0.52) for jet area-based MR grade, 0.28 (95% CI: 0.11 to 0.45) for VC measurements, and 0.37 (95% CI: 0.16 to 0.58) for PISA measurements. Significant univariate predictors of substantial interobserver agreement for: 1) jet area-based MR grade was functional etiology (p = 0.039); 2) VC was central MR (p = 0.013) and identifiable effective regurgitant orifice (p = 0.049); and 3) PISA was presence of a central MR jet (p = 0.003), fixed proximal flow convergence (p = 0.025), and functional etiology (p = 0.049). Significant multivariate predictors of raw interobserver agreement > or =80% included: 1) for VC, identifiable effective regurgitant orifice (p = 0.035); and 2) for PISA, central regurgitant jet (p = 0.02). CONCLUSIONS The VC and PISA measurements for distinction of severe versus nonsevere MR are only modestly reliable and associated with suboptimal interobserver agreement. The presence of an identifiable effective regurgitant orifice improves reproducibility of VC and a central regurgitant jet predicts substantial agreement among multiple observers of PISA assessment.

Aortic annular sizing for transcatheter aortic valve replacement using cross-sectional 3-dimensional transesophageal echocardiography.

OBJECTIVES This study compared cross-sectional three-dimensional (3D) transesophageal echocardiography (TEE) to two-dimensional (2D) TEE as methods for predicting aortic regurgitation after transcatheter aortic valve replacement (TAVR). BACKGROUND Data have shown that TAVR sizing using cross-sectional contrast computed tomography (CT) parameters is superior to 2D-TEE for the prediction of paravalvular aortic regurgitation (AR). Three-dimensional TEE can offer cross-sectional assessment of the aortic annulus but its role for TAVR sizing has been poorly elucidated. METHODS All patients had severe symptomatic aortic stenosis and were treated with balloon-expandable TAVR in a single center. Patients studied had both 2D-TEE and 3D imaging (contrast CT and/or 3D-TEE) of the aortic annulus at baseline. Receiver-operating characteristic curves were generated for each measurement parameter using post-TAVR paravalvular AR moderate or greater as the state variable. RESULTS For the 256 patients studied, paravalvular AR moderate or greater occurred in 26 of 256 (10.2%) of patients. Prospectively recorded 2D-TEE measurements had a low discriminatory value (area under the curve = 0.52, 95% confidence interval: 0.40 to 0.63, p = 0.75). Average cross-sectional diameter by CT offered a high degree of discrimination (area under the curve = 0.82, 95% confidence interval: 0.73 to 0.90, p < 0.0001) and mean cross-sectional diameter by 3D-TEE was of intermediate value (area under the curve = 0.68, 95% confidence interval: 0.54 to 0.81, p = 0.036). CONCLUSIONS Cross-sectional 3D echocardiographic sizing of the aortic annulus dimension offers discrimination of post-TAVR paravalvular AR that is significantly superior to that of 2D-TEE. Cross-sectional data should be sought from 3D-TEE if good CT data are unavailable for TAVR sizing.

Utility of Right Ventricular Tei Index in the Noninvasive Evaluation of Chronic Thromboembolic Pulmonary Hypertension Before and After Pulmonary Thromboendarterectomy

OBJECTIVES We evaluated the utility of tissue Doppler-derived right ventricular (RV) Tei (or myocardial performance) index in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE) and assessed correlations with mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO). BACKGROUND The assessment of RV function is limited with 2-dimensional echocardiography. The RV Tei index, an indicator of RV myocardial performance, is derived by Doppler measurements and is unaffected by RV geometry. The use of tissue Doppler imaging (at the lateral tricuspid annulus) for RV Tei index calculation is simple and eliminates the need for pulsed-wave Doppler recordings of both RV inflow and outflow. METHODS Ninety-three patients with CTEPH were prospectively studied along with 13 control patients. Right ventricular tissue Doppler imaging and right heart catheterization were performed before and after PTE. Right ventricular Tei index was compared with values of mPAP, PVR, and CO with the use of linear regression. RESULTS Right ventricular Tei index was 0.52 +/- 0.19 in patients with CTEPH and 0.27 +/- 0.09 in control patients (p < 0.0001). After PTE, RV Tei index decreased to 0.33 +/- 0.10 (p < 0.0001). Pulmonary vascular resistance correlated well with RV Tei index before (r = 0.78, p < 0.0001) and after (r = 0.67, p < 0.0001) surgery. Also, the absolute change in Tei index in each patient after PTE correlated well with the concomitant change in PVR (r = 0.75, p < 0.0001). RV Tei index did not correlate as well with mPAP (pre-operatively: r = 0.55, p < 0.0001; post-operatively: r = 0.26, p = 0.03) or CO (pre-operatively: r = 0.57, p < 0.0001; post-operatively: r = 0.43, p < 0.0001). CONCLUSIONS These results demonstrate a correlation between RV Tei index and right heart hemodynamics (particularly PVR) in CTEPH. Because PVR is difficult to estimate noninvasively -- and yet correlates with disease severity -- the RV Tei index may be a valuable noninvasive parameter for monitoring disease severity in CTEPH and outcome after PTE.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

The phosphodiesterase 5A inhibitor tadalafil restores normal blood flow regulation in exercising skeletal muscle of patients with Becker muscular dystrophy. A Shot in the Arm for Muscular Dystrophy Becker muscular dystrophy (BMD), characterized by progressive skeletal muscle wasting, is caused by mutations in the muscle protein dystrophin. Preclinical research in the dystrophin-deficient mdx mouse model of a related disease Duchenne muscular dystrophy shows that inhibitors of phosphodiesterase 5 (PDE5)—which boosts guanosine 3′,5′-monophosphate (cGMP), the downstream target of nitric oxide (NO) in vascular smooth muscle—alleviate some features of the dystrophic phenotype including vasospasm of skeletal muscle microvessels that can lead to muscle injury and fatigue. The challenge is to determine whether these compelling results in mice can be translated to benefit human patients with muscular dystrophy. In a new study, Martin et al. assessed exercise-induced attenuation of reflex sympathetic vasoconstriction in the muscles of 10 patients with BMD and 7 age-matched healthy male controls. This is a protective mechanism that optimizes perfusion of skeletal muscle to meet the metabolic demands of exercise. Reflex vasoconstriction was induced by simulated orthostatic stress and was measured as the decrease in forearm muscle oxygenation using near-infrared spectroscopy. The authors took the measurements when the forearm muscles were rested or lightly exercised in the form of a rhythmic handgrip. First, the investigators showed that exercise-induced attenuation of reflex vasoconstriction was defective in 9 of 10 patients with BMD in whom the common dystrophin mutations disrupt targeting of neuronal NO synthase (nNOS) to the muscle sarcolemma (the response was preserved in one patient in whom nNOS was localized to the muscle sarcolemma). Then, in a double-blind randomized placebo-controlled crossover trial, the authors showed that normal blood flow regulation was fully restored in eight of nine patients by a single oral 20-mg dose of the drug tadalafil, a specific PDE5 inhibitor. These findings support an essential role for sarcolemmal nNOS in modulating sympathetic vasoconstriction in exercising human skeletal muscles and implicate PDE5 inhibition as a putative therapeutic strategy for treating BMD. Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3′,5′-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

Comparison of Left Ventricular Outflow Geometry and Aortic Valve Area in Patients With Aortic Stenosis by 2-Dimensional Versus 3-Dimensional Echocardiography

The present study sought to elucidate the geometry of the left ventricular outflow tract (LVOT) in patients with aortic stenosis and its effect on the accuracy of the continuity equation-based aortic valve area (AVA) estimation. Real-time 3-dimensional transesophageal echocardiography (RT3D-TEE) provides high-resolution images of LVOT in patients with aortic stenosis. Thus, AVA is derived reliably with the continuity equation. Forty patients with aortic stenosis who underwent 2-dimensional transthoracic echocardiography (2D-TTE), 2-dimensional transesophageal echocardiography (2D-TEE), and RT3D-TEE were studied. In 2D-TTE and 2D-TEE, the LVOT areas were calculated as π × (LVOT dimension/2)(2). In RT3D-TEE, the LVOT areas and ellipticity ([diameter of the anteroposterior axis]/[diameter of the medial-lateral axis]) were evaluated by planimetry. The AVA is then determined using planimetry and the continuity equation method. LVOT shape was found to be elliptical (ellipticity of 0.80 ± 0.08). Accordingly, the LVOT areas measured by 2D-TTE (median 3.7 cm(2), interquartile range 3.1 to 4.1) and 2D-TEE (median 3.7 cm(2), interquartile range 3.1 to 4.0) were smaller than those by 3D-TEE (median 4.6 cm(2), interquartile range 3.9 to 5.3; p <0.05 vs both 2D-TTE and 2D-TEE). RT3D-TEE yielded a larger continuity equation-based AVA (median 1.0 cm(2), interquartile range 0.79 to 1.3, p <0.05 vs both 2D-TTE and 2D-TEE) than 2D-TTE (median 0.77 cm(2), interquartile range 0.64 to 0.94) and 2D-TEE (median 0.76 cm(2), interquartile range 0.62 to 0.95). Additionally, the continuity equation-based AVA by RT3D-TEE was consistent with the planimetry method. In conclusion, RT3D-TEE might allow more accurate evaluation of the elliptical LVOT geometry and continuity equation-based AVA in patients with aortic stenosis than 2D-TTE and 2D-TEE.

Automated 3-dimensional quantification of noncalcified and calcified coronary plaque from coronary CT angiography

INTRODUCTION We aimed to develop an automated algorithm (APQ) for accurate volumetric quantification of non-calcified (NCP) and calcified plaque (CP) from coronary CT angiography (CCTA). METHODS APQ determines scan-specific attenuation thresholds for lumen, NCP, CP and epicardial fat, and applies knowledge-based segmentation and modeling of coronary arteries, to define NCP and CP components in 3D. We tested APQ in 29 plaques for 24 consecutive scans, acquired with dual-source CT scanner. APQ results were compared to volumes obtained by manual slice-by-slice NCP/CP definition and by interactive adjustment of plaque thresholds (ITA) by 2 independent experts. RESULTS APQ analysis time was <2 sec per lesion. There was strong correlation between the 2 readers for manual quantification (r = 0.99, p < 0.0001 for NCP; r = 0.85, p < 0.0001 for CP). The mean HU determined by APQ was 419 +/- 78 for luminal contrast at mid-lesion, 227 +/- 40 for NCP upper threshold, and 511 +/- 80 for the CP lower threshold. APQ showed a significantly lower absolute difference (26.7 mm(3) vs. 42.1 mm(3), p = 0.01), lower bias than ITA (32.6 mm(3) vs 64.4 mm(3), p = 0.01) for NCP. There was strong correlation between APQ and readers (R = 0.94, p < 0.0001 for NCP volumes; R = 0.88, p < 0.0001, for CP volumes; R = 0.90, p < 0.0001 for NCP and CP composition). CONCLUSIONS We developed a fast automated algorithm for quantification of NCP and CP from CCTA, which is in close agreement with expert manual quantification.

Right Atrial Cavotricuspid Isthmus: Anatomic Characterization with Multi–Detector Row CT

PURPOSE To retrospectively evaluate the anatomic characteristics of the right atrial cavotricuspid isthmus (CTI) by using 64-section multi-detector row computed tomography (CT). MATERIALS AND METHODS Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. The anatomic region of the CTI was evaluated in 201 patients (116 men and 85 women; mean age, 58 years +/- 11 [standard deviation]) who underwent coronary multi-detector row CT. CTI length was assessed along three parallel isthmic levels (paraseptal, central, and inferolateral). Central isthmus depth was classified as straight (3 mm), concave (>3 to </=5 mm), or pouchlike (>5 mm). Measurements were obtained during three cardiac phases: midsystole, middiastole, and atrial contraction. Subthebesian recess dimensions and eustachian ridge width were measured. Distances from the atrioventricular node artery to the coronary sinus, from the right coronary artery (RCA) to the inferior vena cava, and from the RCA to the tricuspid valve annulus were measured. Software was used for statistical analysis. RESULTS At middiastole, the paraseptal isthmus (mean length, 20 mm +/- 3.5; range, 11-34 mm) was significantly shorter than the central isthmus (24 mm +/- 4.3; range, 12-43 mm) and the central isthmus was shorter than the inferolateral isthmus (27 mm +/- 4.8; range, 13-45 mm) (P < .001). The longest CTI measurements were obtained during midsystole, and the shortest were obtained during atrial contraction (40% variation per cardiac cycle). Isthmus contraction occurred primarily in the posterior segment of the central isthmus (RCA to inferior vena cava distance). At middiastole, the central isthmus was straight in 8% of patients, concave in 47% of patients, and pouchlike (>5 mm) in 45% of patients. The mean depth was greater during atrial contraction (6.3 mm +/- 2.1) than in midsystole (4.3 mm +/- 1.5) and middiastole (5.1 mm +/- 1.8) (32% variation during cardiac cycle). A subthebesian recess greater than 5 mm deep was identified in 45% of patients. In 24% of patients, a thick eustachian ridge greater than 4 mm was seen. The atrioventricular node artery passed close to the coronary sinus wall (mean distance, 2.1 mm +/- 0.7; range, 1-6 mm). CONCLUSION Cardiac multi-detector row CT provides extensive information regarding the size and morphology of the CTI and its related structures.

Reproducibility of coronary artery plaque volume and composition quantification by 64-detector row coronary computed tomographic angiography: An intraobserver, interobserver, and interscan variability study

BACKGROUND Interscan variability of coronary arterial plaque volume and composition quantification with coronary computed tomographic angiography (CCTA), an important attribute when considering CCTA as a serial modality, has not been examined. OBJECTIVE We sought to systematically determine intraobserver- and interobserver-interscan reproducibility of these measures. METHODS Two blinded, experienced readers independently evaluated proximal coronary segments on CCTAs from 30 patients who underwent 2 scans within 200 days (median, 124 days; interquartile range, 49-155 days) without experiencing an interim acute coronary event. Readers recorded number of plaques and, in plaques that met a preset minimal length criterion, quantified total, calcified plaque (CP), and noncalcified plaque (NCP) volumes and percentage of total plaque volume occupied by NCP. RESULTS Of 89 total segments studied, 36 contained detectable plaque, and 26 met criterion for quantification. Intraobserver, interobserver, and interscan agreements for normal segments were 100%. Intraobserver-interscan correlations of total, CP, and NCP volumes and percentage of NCP were excellent (r=0.93-0.97, P values<0.001). Interobserver-interscan correlations for all measures were also very good (r=0.81-0.96, P values<0.001). Variability in plaque volume quantification was significant, exceeding 60% of the averaged paired plaque volumes in the best-case scenario (interobserver-interscan CP volume). Quantification of percentage of NCP composition by volume was more consistent, with <24% variation in the worst-case scenario (interobserver-interscan). CONCLUSION CCTA shows promise for quantifying serial coronary plaque change. Currently, the most robust measure seems to be percentage of plaque composition, rather than plaque volume. For smaller plaques, volume quantification remains challenging.

Imaging of Patent Foramen Ovale with 64-Section Multidetector CT

PURPOSE To investigate the feasibility of 64-section multidetector computed tomography (CT) by using CT angiography (a) to demonstrate anatomic detail of the interatrial septum pertinent to the patent foramen ovale (PFO), and (b) to visually detect left-to-right PFO shunts and compare these findings in patients who also underwent transesophageal echocardiography (TEE). MATERIALS AND METHODS In this institutional review board-approved HIPAA-compliant study, electrocardiographically gated coronary CT angiograms in 264 patients (159 men, 105 women; mean age, 60 years) were reviewed for PFO morphologic features. The length and diameter of the opening of the PFO tunnel, presence of atrial septal aneurysm (ASA), and PFO shunts were evaluated. A left-to-right shunt was assigned a grade according to length of contrast agent jet (grade 1, <or=1 cm; grade 2, >1 cm to 2 cm; grade 3, >2 cm). In addition, 23 patients who underwent both modalities were compared (Student t test and linear regression analysis). A difference with P < .05 was significant. RESULTS A flap valve, seen in 101 (38.3%) patients, was patent at the entry into the right atrium (PFO) in 62 patients (61.4% of patients with flap valve, 23.5% of total patients). A left-to-right shunt was detected in 44 (16.7% of total) patients (grade 1, 61.4%; grade 2, 34.1%; grade 3, 4.5%). No shunt was seen in patients without a flap valve. Mean length of PFO tunnel was 7.1 mm in 44 patients with a shunt and 12.1 mm in 57 patients with a flap valve without a shunt (P < .0001). In patients with a tunnel length of 6 mm or shorter, 92.6% of the shunts were seen. ASA was seen in 11 (4.2%) patients; of these patients, a shunt was seen in seven (63.6%). In 23 patients who underwent CT angiography and TEE, both modalities showed a PFO shunt in seven. CONCLUSION Multidetector CT provides detailed anatomic information about size, morphologic features, and shunt grade of the PFO. Shorter tunnel length and septal aneurysms are frequently associated with left-to-right shunts in patients with PFO.

Bachmann Bundle and Its Arterial Supply: Imaging with Multidetector CT—Implications for Interatrial Conduction Abnormalities and Arrhythmias

PURPOSE To retrospectively investigate anatomy of Bachmann Bundle (BB) and its vascular supply at 64-section multidetector computed tomography (CT) in healthy patients and patients with abnormalities. MATERIALS AND METHODS The institutional review board approved this HIPAA-compliant study and waived informed consent. Clinical histories, electrocardiograms (ECGs), and coronary 64-section multidetector CT angiograms in 317 patients were reviewed (healthy group, 164; group with abnormalities, 153). Among patients with abnormalities, 68 had atrial fibrillation (AF) or interatrial conduction block (IAB) (P wave duration, >or=120 msec), 46 had severe coronary artery disease (CAD) (>or=70% stenosis of coronary artery giving rise to sinuatrial node [SAN] artery), and 39 had severe CAD and an abnormal ECG (AF or IAB). Length, anteroposterior and superoinferior diameters, attenuation, and vascular supply of BB were studied. Student t test for continuous variables and contingency tables for categorical variables were used. RESULTS BB was visualized, to greater degree, in the healthy group (90.2% vs 73.9% for group with abnormalities, P < .001). Visualization of BB was similar among subgroups with abnormalities: 71.7% in patients with severe CAD, 73.5% in patients with abnormal ECG, and 76.9% in patients with severe CAD and abnormal ECG. BB measurements were similar for both groups. Patients with nonvisualized BB displayed lower overall mean attenuation in the region, with -30.6 HU +/- 33.4 (standard deviation), but mean attenuation in healthy patients was 51.3 HU +/- 59.9 (P < .001). This finding suggests fatty infiltration. BB and BB region were mainly supplied by the right SAN artery (55.5%), followed by the left SAN artery (39.6%) and both SAN arteries (4.9%). In the group with abnormalities, there was a significant difference for SAN artery nonvisualization between those with and without identifiable BB (P = .001). CONCLUSION BB and its vascular supply can easily be demarcated on cardiac CT images. BB was visualized less in patients with severe CAD and abnormal ECG, a finding that suggests that disease of BB fibers may play a role in development of atrial arrhythmias.