Figure 1. Continued

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gathers data noninvasively and rapidly in a single heartbeat, re-constructs local electrograms, permits voltage and activation mappingof both ventricles simultaneously, and, by virtue of its ability forepicardial imaging, may detect nascent disease.

Niraj Varma, MA, DM,* Maria Strom, PhD, Mina K. Chung, MD

*J2-2 Cardiac Electrophysiology, Cleveland Clinic, Cleveland,Ohio 44195. E-mail: varman@ccf.org

http://dx.doi.org/10.1016/j.jcmg.2013.04.019

Please note: Research support was provided by CardioInsight Technologies, Inc. All

analyses were initiated by Drs. Varma and Chung without sponsor involvement. The

authors thank Paul Schoenhagen, MD (Imaging Institute, Cleveland Clinic). Dr.

Strom is a paid employee of and holds stock in CardioInsight Technologies, Inc. All

other authors have reported that they have no relationships relevant to the content of

this paper to disclose.

R E F E R E N C E S

1. Corrado D, Basso C, Leoni L, et al. Three-dimensional electro-anatomic voltage mapping increases accuracy of diagnosing arrhyth-mogenic right ventricular cardiomyopathy/dysplasia. Circulation 2005;111:3042–50.

2. Berruezo A, Fernandez-Armenta J, Mont L, et al. Combined endocardialand epicardial catheter ablation in arrhythmogenic right ventriculardysplasia incorporating scar dechanneling technique. Circ ArrhythmElectrophysiol 2012;5:111–21.

3. Ramanathan C, Ghanem RN, Jia P, Ryu K, Rudy Y. Noninvasive elec-trocardiographic imaging for cardiac electrophysiology and arrhythmia.Nat Med 2004;10:422–8.

4. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenicright ventricular cardiomyopathy/dysplasia: proposed modification of thetask force criteria. Circulation 2010;121:1533–41.

5. Varma N, Jia P, Ramanathan C, Rudy Y. RV electrical activation in heartfailure during right, left, and biventricular pacing. J Am Coll Cardiol Img2010;3:567–75.

Impact of Regurgitant Orifice Heightfor Mechanism of AorticRegurgitation

A classification of aortic regurgitation (AR) by transesophageal echo-cardiography (TEE) has been considered a critical pre-operative assess-ment, particularly for valve repair operations (1). This study aimed toevaluate the mechanism of isolated AR by quantitative analysis of aorticvalve apparatus (AVAp) by 3-dimensional (3D) TEE using novel soft-ware and to identify a discriminatory index for AR mechanisms.

Figure 1. 3-Dimensional Measurements of AVAp

To contour AVAp automatically, the 2 coronary ostium (blue points), the 3 commissures of aortic valve (green points), the 3 nadirs of cusp (violet points), and the 3leaflet tips (yellow points) are included and, if necessary, manually corrected. The following parameters were measured automatically (A) aortic root area: annulus(yellow), sinus Valsalva (violet), sinotubular junction (blue); (B) cusp volume: LCC (yellow), RCC (blue), NCC (violet); (C) leaflet length: LCC leaflet (yellow dottedline), RCC leaflet (blue dotted line), NCC leaflet (violet dotted line); (D) regurgitant orifice height (yellow arrow). AVAp ¼ aortic valve apparatus; L ¼ left; LCC ¼ left-coronary cusp; NCC ¼ noncoronary cusp; R ¼ right; RCC ¼ right-coronary cusp.

Figure 2. 2D TEE and Volume-Rendered 3D TEE Representations of AVAp in the 3 AR Types

(A) Type I, dilation of aortic root; (B) type II, leaflet prolapse of right-coronary cusp leaflet; and (C) type III, retraction of all leaflets. Blue points: coronary ostium, greenpoints: aortic valve commissures, violet points: cusp nadirs, and yellow points: leaflet tips. 2D ¼ 2-dimensional; 3D ¼ 3-dimensional; AR ¼ aortic regurgitation; TEE ¼transesophageal echocardiography.

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We retrospectively identified 182 patients who underwent surgicalcorrection for isolated AR fromDecember 2007 to February 2011 and15 age-, sex-, and body-surface-area–matched controls. Patients withaortic dissection, infective endocarditis, complexARmechanisms, andcongenital valve dysfunction were excluded. Seventy patients with ARwere assigned to 1 of 3 pathological categories on the basis of surgicalinspection, as follows: 1) type I, dilation of aortic root (n ¼ 20); 2)type II, leaflet prolapse with flail leaflet, transverse fibrous band, andfenestration (n ¼ 36); and 3) type III, restricted leaflet due to rigidvalve and calcifications (n ¼ 14). Pre-operative TEE was conductedwithin 3 months before surgery using the iE33 ultrasound system(Philips Medical Systems, Bensalem, Pennsylvania). 3D datasetswere analyzed using novel 3D, knowledge-based, valve-modelingsoftware (Siemens Medical Solutions, Mountain View, California)(2). Regurgitant orifice height (ROH) was measured as the 3Dperpendicular distance from the annular plane to the center of the3 leaflet tips in end-diastolic frame (Fig. 1D).

In pre-operative clinical characteristics, there were no differencesbetween the 3 AR pathological categories, with the exception of

eccentric jet flow. Analysis in 15 random patients showed goodintraobserver and interobserver reproducibility of each 3D parameter.Of 85 total patients, 81 (95%) had adequate 3D TEE data forquantification of AVAp and were included in the analysis. Figure 2shows representative 2-dimensional (2D) TEE and volume-rendered 3D TEE datasets of AVAp in the 3 AR types. Comparedwith controls, ROH was larger in type I (9.5 � 1.6 mm; p < 0.001)and smaller in type II (2.9� 0.9 mm; p< 0.05). In type III, all leafletlengths were shorter than those in the controls (p< 0.05). Correlationbetween ROH and sinotubular junction (STJ)/annulus area ratio (r¼0.81; p <0.001) was greater than correlation between 2D coaptationheight and STJ/annulus diameter ratio. ROH was of the highestdiscriminatory index for types I and II (areas under the curve: 1.0 [p<0.001] and 0.93 [p < 0.001], respectively) in 2D and 3D TEEmeasurement parameters. The best cutoff values for types I and IIwereROH $7 mm (sensitivity 100%, specificity 100%) and <4 mm(sensitivity 74%, specificity 94%), respectively.

The main accomplishment was successful quantitative 3D eval-uation of AVAp in various AR types: type I was distinguished by a

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large ROH; type II, by a small ROH; and type III, by short leafletlengths. STJ/annulus area ratio correlated well with ROH regardlessof AR type. ROH was the highest discriminatory index for types Iand II. This report is not a technical validation of the accuracy ofthis software for quantitative analysis of AVAp. However, theprevious study using this software program to compute precisemorphological quantification of AVAp from 3D TEE andcomputed tomography data demonstrated a strong intermodalityand intersubject correlation (2). As a clinical implication, the presentstudy by 3D TEE may potentially help the surgical team torecognize in-depth anatomic abnormalities or the classification withconvincing quantitative information for surgical planning.

Kentaro Shibayama, MD,* Hiroyuki Watanabe, MD,Shunsuke Sasaki, MD, Keitaro Mahara, MD,Minoru Tabata, MD, Toshihiro Fukui, MD,Shuichiro Takanashi, MD, Tetsuya Sumiyoshi, MD,Hitonobu Tomoike, MD, Takahiro Shiota, MD

*Cedars-Sinai Heart Institute, 127 South San Vicente Boulevard,Suite A3411 (Takahiro Shiota), Los Angeles, California 90048. E-mail: shibao_k@hotmail.com

http://dx.doi.org/10.1016/j.jcmg.2013.03.011

Please note: The authors thank Sakakibara Heart Institute for their generous support of

this project.

R E F E R E N C E S

1. le Polain de Waroux JB, Pouleur AC, Goffinet C, et al. Functionalanatomy of aortic regurgitation: accuracy, prediction of surgical repair-ability, and outcome implications of transesophageal echocardiography.Circulation 2007;116:I264–9.

2. Calleja A, Thavendiranathan P, Ionasec RI, et al. Automated quantitative3-dimensional modeling of the aortic valve and root by 3-dimensionaltransesophageal echocardiography in normals, aortic regurgitation, andaortic stenosis: comparison to computed tomography in normals andclinical implications. Circ Cardiovasc Imaging 2013;6:99–108.

Coronary Plaque Composition andPost-PCI Complications in NSTEMITheability to identify those characteristics of coronaryplaquemorphologythat are associated with a higher risk for microvascular impairment andmyocardial injury after percutaneous intervention (PCI) may provide anopportunity to improve clinical outcomes in patients with non–ST-segment myocardial infarction (NSTEMI) treated with PCI (1,2). Weinvestigated the impact of virtual histology intravascular ultrasound(IVUS)-verified pre-PCI coronary plaque composition on peri-procedural microvascular function as assessed using microvascular resis-tance (mVR)measurements in patients with NSTEMI undergoing PCI.

Thirty-four patients were enrolled (Fig. 1). Serum troponin T(TnT) levels were measured on admission, immediately prior to and6 hours after PCI. The target coronary lesion was crossed by a dual-sensor–equipped guidewire (Doppler and Pressure Combo Wire,Volcano Corporation, San Diego, California). Prior to PCI and inthe presence of epicardial stenosis, microvascular resistance (pre-PCI mVR) was calculated with coronary wedge pressure (Pw)-basedcorrection, as follows: Pa(1/APV)[(Pd-Pw)/(Pa-Pw)], where Pa

denotes aortic pressure, Pd is distal coronary pressure, and APV is anaverage peak velocity. After obtaining pre-PCI hemodynamicmeasurements, IVUS measurements were recorded as describedelsewhere (3). Post-PCI hyperemic mVR was calculated as Pd/APV.The peri-procedural change in mVR (DmVR) was calculated as Post-PCI mVR – Pre-PCI mVR. Paired t test and linear regressionanalysis were used where appropriate. Normal distribution wasachieved for TnT values by logarithmic transformation. Multivariatelinear regression analysis was applied to identify the independentpredictors of DmVR, including pre-PCI mVR, all IVUS parameters,total plaque volume, lesion and stent lengths, angiographic percentdiameter stenosis, and the presence of thrombus on angiography.

There was a significant correlation between DmVR and DTnT(r ¼ 0.454; p ¼ 0.03). The necrotic core/dense calcium ratio wasthe only VH-IVUS characteristic correlated with pre-PCI mVR(r¼ 0.735; p< 0.001). Similarly, the percent of necrotic core volume(%NCV) was the only IVUS parameter correlated with DmVR (r ¼0.601; p < 0.001) and post-PCI mVR (r ¼ 0.55; p ¼ 0.002). DTnTwas correlatedwith%NCV (r¼ 0.473; p¼ 0.015). In themultivariatemodel, DmVR was predicted by %NCV (b ¼ 0.472; p ¼ 0.01), fol-lowed by pre-PCI mVR (b¼ 0.343; p¼ 0.045). The best cutoff valueof %NCV for the prediction of an increase in post-PCI mVR was18, with a sensitivity of 84% and a specificity of 66% (area under thecurve ¼ 0.826; 95% confidence interval: 0.67 to 0.96).

This study demonstrated that in patients undergoing PCIfor NSTEMI, the ratio of necrotic core to dense calcium wasassociated with the extent of baseline pre-PCI microvascular injury,and that %NCV in the culprit lesion predicted the extent of post-PCI increase in mVR. In other words, the features suggestive ofgreater lesion instability were associated with more extensivemicrovascular obstruction at presentation, as well as PCI-relatedimpairment of microvascular perfusion in NSTEMI. Althoughprevious IVUS studies have demonstrated a relationship betweennecrotic core component and post-PCI embolization (4), in thecurrent study, the extent of PCI-related microvascular impair-ment, which was assessed precisely by the difference between pre-and post-PCI MR values, was shown to have been predicted by thepercentage (but not the absolute amount) of necrotic core volumeacross the entire lesion segment. Moreover, the status of microcir-culation at baseline also emerged as one of the major determinantsof peri-procedural microvascular injury, supporting the findings of arecently published study (5). Nonetheless, the results of this studyshould be interpreted with consideration of the limitation of rela-tively small patient numbers, and therefore additional predictors ofbaseline and post-PCI mVR may not have been detected.

In summary, in the NSTEMI setting, the proportion of necroticcore content in the target lesion was associated with the extent ofboth pre- and peri-procedural microvascular dysfunction and post-procedural myonecrosis. The pre-procedural identification of thosecoronary plaques most likely to induce microvascular injury duringthe PCI procedure may allow the strategies of protection of themicrovasculature at the time of PCI to improve clinical outcomes inpatients with NSTEMI.

Cansu Akdeniz, MD, Sabahattin Umman, MD,Abdullah Kaplan, MD, Yilmaz Nisanci, MD, Berrin Umman, MD,Zehra Bu�gra, MD, Emre Aslanger, MD,Derek J. Hausenloy, MD, PhD, Akar Yilmaz, MD, Nihat Polat, MD,Murat Sezer, MD*