Diagnosing Coarctation - A Clinical Dilemma-...odds ratio, 38.2; 95% confidence interval,...

Greggory R. DeVore, M.D. Clinical Professor

Department of Obstetrics and Gynecology David Geffen School of Medicine at UCLA

Los Angeles, CA

Director Fetal Diagnostic Centers Pasadena, Tarzana, Lancaster, CA

Diagnosing Coarctation- A Clinical Dilemma-

Coarctation of the Aorta

• 5% to 8% of Congenital Heart Defects

• Does Not Cause Fetal Circulatory Compromise

• Aortic Isthmus Not an Essential Component of Fetal Circulation

• Prenatal Detection 7% to 50%

• False-Positive Rate as High as 65%

Prenatal

ChamberDisproportion


•After birth and ductal closure, a critical CoA will result in poor perfusion of the lower body and acidemia that together with an increase in left heart afterload may result in acute circulatory shock

•Most common life-threatening cardiovasular malformation overlooked in the neonatal period

•60% diagnosed after discharge from the hospital

Postnatal

Circulation. 2009 Aug 4;120(5):447-58.


Pulse-Oximetry Screening

In 2011, the U.S. Department of Health and Human Services added critical congenital heart disease (CCHD) to the list of conditions recommended to states for universal newborn screening using pulse oximetry


Pediatrics. 2018 May;141(5). pii: e20174065. doi: 10.1542/peds.2017-4065.

• Screened 77,148 newborns and reported 6 false-negatives, of which 4 had CoA.

• No fetus with CoA was identified in the screen-positive group.

Meta-Analysis

February 21, 2017 Circulation. 2017;135:772–785. DOI: 10.1161/CIRCULATIONAHA.116.024068772

ORIGINAL RESEARCH ARTICLE

BACKGROUND: Prenatal diagnosis of coarctation of the aorta (CoA) is still challenging and affected by high rates of false-positive diagnoses. The aim of this study was to ascertain the strength of association and to quantify the diagnostic accuracy of different ultrasound signs in predicting CoA prenatally.

METHODS: Medline, Embase, CINAHL, and Cochrane databases were searched. Random-effects and hierarchical summary receiver operating characteristic model meta-analyses were used to analyze the data.

RESULTS: Seven hundred ninety-four articles were identified, and 12 (922 fetuses at risk for CoA) articles were included. Mean mitral valve diameter z score was lower (P<0.001) and the mean tricuspid valve diameter z score was higher in fetuses with CoA than in those without CoA (P=0.01). Mean aortic valve diameter z score was lower in fetuses with CoA than in healthy fetuses (P!0.001), but the ascending aorta diameter, expressed as z score or millimeters, was similar between groups (P=0.07 and 0.47, respectively). Mean aortic isthmus diameter z scores measured either in sagittal (P=0.02) or in 3-vessel trachea view (P<0.001) were lower in fetuses with CoA. Conversely, the mean pulmonary artery diameter z score, the right/left ventricular and pulmonary artery/ascending aorta diameter ratios were higher (P<0.001, P=0.02, and P=0.02, respectively) in fetuses with CoA in comparison with controls, although aortic isthmus/arterial duct diameter ratio was lower in fetuses with CoA than in those without CoA (P<0.001). The presence of coarctation shelf and aortic arch hypoplasia were more common in fetuses with CoA than in controls (odds ratio, 26.0; 95% confidence interval, 4.42–153; P<0.001 and odds ratio, 38.2; 95% confidence interval, 3.01–486; P=0.005), whereas persistent left superior vena cava (P=0.85), ventricular septal defect (P=0.12), and bicuspid aortic valve (P=0.14) did not carry an increased risk for this anomaly. Multiparametric diagnostic models integrating different ultrasound signs for the detection of CoA were associated with an increased detection rate.

CONCLUSIONS: The detection rate of CoA may improve when a multiple-criteria prediction model is adopted. Further large multicenter studies sharing the same imaging protocols are needed to develop objective models for risk assessment in these fetuses.

Risk Factors for Coarctation of the Aorta on Prenatal UltrasoundA Systematic Review and Meta-Analysis

© 2016 American Heart Association, Inc.

Correspondence to: Francesco D’Antonio, MD, PhD, Department of Clinical Medicine, Faculty of Health Sciences, UiT - The Arctic University of Norway, Hansine Hansens veg 18, 9019 Tromsø, Norway. E-mail [email protected]

Sources of Funding, see page 784

Key Words: aortic coarctation "!heart defects, congenital "!fetal echocardiography " prenatal diagnosis

Alessandra Familiari, MDMaddalena Morlando, MDAsma Khalil, MDSven-Erik Sonesson,

MD,!PhDCarolina Scala, MDGiuseppe Rizzo, MDGelsomina Del Sordo, MDChiara Vassallo, MDMaria Elena Flacco, MDLamberto Manzoli, MDAntonio Lanzone,

MD,!PhDGiovanni Scambia,

MD,!PhDGanesh Acharya, MD, PhDFrancesco D’Antonio,

MD,!PhD

Dow

nloaded from http://ahajournals.org by on O

ctober 13, 2019

2017

February 21, 2017 Circulation. 2017;135:772–785. DOI: 10.1161/CIRCULATIONAHA.116.024068772

ORIGINAL RESEARCH ARTICLE

BACKGROUND: Prenatal diagnosis of coarctation of the aorta (CoA) is still challenging and affected by high rates of false-positive diagnoses. The aim of this study was to ascertain the strength of association and to quantify the diagnostic accuracy of different ultrasound signs in predicting CoA prenatally.

METHODS: Medline, Embase, CINAHL, and Cochrane databases were searched. Random-effects and hierarchical summary receiver operating characteristic model meta-analyses were used to analyze the data.

RESULTS: Seven hundred ninety-four articles were identified, and 12 (922 fetuses at risk for CoA) articles were included. Mean mitral valve diameter z score was lower (P<0.001) and the mean tricuspid valve diameter z score was higher in fetuses with CoA than in those without CoA (P=0.01). Mean aortic valve diameter z score was lower in fetuses with CoA than in healthy fetuses (P!0.001), but the ascending aorta diameter, expressed as z score or millimeters, was similar between groups (P=0.07 and 0.47, respectively). Mean aortic isthmus diameter z scores measured either in sagittal (P=0.02) or in 3-vessel trachea view (P<0.001) were lower in fetuses with CoA. Conversely, the mean pulmonary artery diameter z score, the right/left ventricular and pulmonary artery/ascending aorta diameter ratios were higher (P<0.001, P=0.02, and P=0.02, respectively) in fetuses with CoA in comparison with controls, although aortic isthmus/arterial duct diameter ratio was lower in fetuses with CoA than in those without CoA (P<0.001). The presence of coarctation shelf and aortic arch hypoplasia were more common in fetuses with CoA than in controls (odds ratio, 26.0; 95% confidence interval, 4.42–153; P<0.001 and odds ratio, 38.2; 95% confidence interval, 3.01–486; P=0.005), whereas persistent left superior vena cava (P=0.85), ventricular septal defect (P=0.12), and bicuspid aortic valve (P=0.14) did not carry an increased risk for this anomaly. Multiparametric diagnostic models integrating different ultrasound signs for the detection of CoA were associated with an increased detection rate.

CONCLUSIONS: The detection rate of CoA may improve when a multiple-criteria prediction model is adopted. Further large multicenter studies sharing the same imaging protocols are needed to develop objective models for risk assessment in these fetuses.

Risk Factors for Coarctation of the Aorta on Prenatal UltrasoundA Systematic Review and Meta-Analysis

© 2016 American Heart Association, Inc.

Correspondence to: Francesco D’Antonio, MD, PhD, Department of Clinical Medicine, Faculty of Health Sciences, UiT - The Arctic University of Norway, Hansine Hansens veg 18, 9019 Tromsø, Norway. E-mail [email protected]

Sources of Funding, see page 784

Key Words: aortic coarctation "!heart defects, congenital "!fetal echocardiography " prenatal diagnosis

Alessandra Familiari, MDMaddalena Morlando, MDAsma Khalil, MDSven-Erik Sonesson,

MD,!PhDCarolina Scala, MDGiuseppe Rizzo, MDGelsomina Del Sordo, MDChiara Vassallo, MDMaria Elena Flacco, MDLamberto Manzoli, MDAntonio Lanzone,

MD,!PhDGiovanni Scambia,

MD,!PhDGanesh Acharya, MD, PhDFrancesco D’Antonio,

MD,!PhD

Dow

nloaded from http://ahajournals.org by on O

ctober 13, 2019

2017

Sensitivity >90%, Specificity >90%

Meta-AnalysisGomez-Montes

-2014-

Pasquini L, Mellander M, Seale A, et al. Z-scores of the fetal aortic isthmus and duct: an aid to assessing arch hypoplasia. Ultrasound Obstet Gynecol 2007;29:628–33.

Schneider C, McCrindle BW, Carvalho JS, et al. Development of Z-scores for fetal cardiac dimensions from echocardiography. Ultrasound Obstet Gynecol 2005;26:599–605.

Prenatal Diagnosis 2014, 34, 1198–1206

Used Data From 2 Studies To Compute Z-Scores

<28 Weeks

Z-Score -2.45Prenatal Diagnosis 2014, 34, 1198–1206

<28 Weeks


<28 Weeks

Z-Score -2.28

Early Diagnosis <28 Weeks

Cutoff Value for LL Centile +LL Ratio -LL Ratio Study Z-

Scores

Ascending Aorta

(Schneider) Z-Score

<-1.1 <13.5 Centile 3.7 0.2 -2.45

Aortic Isthmus

(3VT) (Pasquini) Z-Score

<-1.2 <11.5 Centile 3.9 0.04 -2.28

Step 1: Posttest odds= Pretest odds x (LR1*LR2) Posttest odds= 3.1 x 3.7 x 3.9 = 44.7

Coarc True Pos=43 False Pos Coarc=14

Pretest Odds 43/14=3.1

Step 2: Posttest Probability= (Pretest odds / Pretest Odds +1) x 100

Posttest Probability = (44.7/(44.7+1) x 100 = 97.2%


<28 Weeks

ROC Curve Area - 0.98

Sensitivity 91% For a FPR of 10%

Specificity of 91% For a FNR of 10%

>28 Weeks

Tricuspid Valve/Mitral Valve Ratio

TV = 1.8 MV = 0.6 Ratio = 2


>28 Weeks

Main Pulmoanry/Ascending Aorta Measurement MPA = 1.1 AAo = 0.4

Ratio = 2.75


>28 Weeks

Late Diagnosis >28 Weeks

Cutoff Value for LL Ratio +LL Ratio -LL Ratio Study Values

TV/MV Ratio > 1.48 2.3 0.5 2

MPA/AscA > 1.85 3.6 0.2 2.75

Step 1: Posttest odds= Pretest odds x (LR1*LR2) Posttest odds= 0.18 x 2.3 x 3.6 = 1.49

Coarc True Pos=9 False Pos Coarc=49

Pretest Odds 9/49=0.18

Step 2: Posttest Probability= (Pretest odds / Pretest Odds +1) x 100

Posttest Probability =[(1.49/(1.49+1)] x 100 = 60%


ROC Curve Area - 0.82

>28 WeeksSensitivity 63%

For a FPR of 10%

Specificity of 43% For a FNR of 10%

Meta-AnalysisArya

-2016-

Prenat Diagn 2016, 36(2) 127-134

Prenat Diagn 2016, 36(2) 127-134

Transverse Aorta and Descending Aorta Angle

Ascending Aorta and Descending Aorta Angle

Normal NormalCoarctation Coarctation

** **

Angle between the AscendingAorta and Descending Aorta

Angle between the AscendingAorta and Transverse Aorta

September, 2018

Correct Equation


69 Fetuses 31: 45% Coarctation 38: 55% No Coarctation

Diastole

Systole

Diastole

Systole

Normal

Ratio >0.56 Abnormal

Diastole

Systole

Diastole

Systole

Coarctation

VTId/VTIs ratio >0.56 had 94% sensitivity and

89% specificity for neonatal CoA.


94% Sensitivity

89% Specificity

Imaging the Sagittal View of the Aortic Arch

Weeks 20 to 24: 27%

Weeks 25 to 38 Weeks: 65%

50 Fetuses with Postnatally Confirmed Coarctation of the Aorta

4-Chamber View Size and Shape

Ventricular Size and Shape

Ventricular Contractility

Globular (Decreased GSI): 31%

Increased Transverse Width: 24%

Increased Area: 22%

4-Chamber Size and Shape

4-CV Size and Shape

Flattened Chamber

24-Segment Sphericity Index of LV

28%-64%

Base 28%

Mid 28%

Apex 64%

>95th Centile

Round Chamber

32%-49%Base 49%

Mid 49%

Apex 32%

<5th Centile

24-Segment Sphericity Index of RV

Left Ventricle <5th Centile

86% 30%

SMALL

Right Ventricle >95th Centile

LARGE

End-Diastolic Area

LV

RV52%

40%

Decreased Fractional Area Change <5th Centile

Abnormal Longitudinal Strain >95th Centile

RV 32%

LV 36%

RV 22% - 45%

LV 40% - 51%

Decreased 24 Segment Fractional Shortening <5th Centile

Can Evaluation of the 4-Chamber ViewUsing Speckle Tracking Analysis

Separate True from False Positives Fetuses Suspected to Have


4-Chamber View Size and Shape

Ventricular Size and Shape Ventricular Contractility

Logistic Regression Analysis54 Fetuses Postnatal

Coarctation

54 Fetuses Postnatal

False-Positive

Atrium

Number CLASSIFICATINGESTATIONAL

AGE (weeks) At First Examination

GESTATIONAL AGE (weeks) at

Last Examination

Prenatal RV/LV Area

Disproportion

Bicuspid Aortic Valve

Aortic Arch Hypoplasia

Aortic Valve Hypoplasia

Sub-Aortic Membrane

Dysplastic Aortic Valve

Unicuspid Aortic Valve

Ventricular Septal Defect

Mitral Valve Abnormality

Supravalvar Mtral Ring

Atrial Septal Defect

Left Superior Vena dava

Partial Anomalous Pulmonary

Venous Return

Right Sided Aortic Arch

Aberrant Right Subclavian

Artery

Common Brachiocephalic

Trunk

Coarctation Shelf

Isolated Left Pulmonary

Artery from Left Ductus Arteriosus

1 Coarctation 39 39 Present Present2 Coarctation 28 32 Present Present Present Present Present Present Present3 Coarctation 21 32 Present Present Present Present4 Coarctation 24 35 Present5 Coarctation 32 35 Present Present Present6 Coarctation 28 28 Present Present Present7 Coarctation 21 30 Present Present8 Coarctation 24 24 Present 29 Coarctation 30 37 Present Present Present Present

10 Coarctation 29 33 Present Present Present Present Present Present Present11 Coarctation 32 32 Present Present Present12 Coarctation 26 26 Present Present Present Present13 Coarctation 24 35 Present Present Present14 Coarctation 25 34 Present Present Present Present15 Coarctation 22 35 Present Present Present Present16 Coarctation 23 35 Present Present Present Present Present Present Present17 Coarctation 31 31 Present Present18 Coarctation 24 37 Present Present Present19 Coarctation 26 35 Present Present Present20 Coarctation 32 37 Present21 Coarctation 28 35 Present Present Present Present22 Coarctation 14 28 Present23 Coarctation 20 36 Present Present Present Present Present24 Coarctation 28 28 Present Present25 Coarctation 22 33 Present Present26 Coarctation 21 32 Present Present Present Present Present27 Coarctation 22 36 Present Present28 Coarctation 23 36 Present Present Present Present Present Present Present29 Coarctation 26 33 Present30 Coarctation 22 28 Present Present Present31 Coarctation 26 36 Present Present Present32 Coarctation 25 33 Present Present Present33 Coarctation 29 35 Present Present Present Present34 Coarctation 20 33 Present Present35 Coarctation 23 3236 Coarctation 29 29 Present Present37 Coarctation 22 30 Present Present38 Coarctation 23 23 Present Present Present Present Present39 Coarctation 33 33 Present Present Present40 Coarctation 20 37 Present Present Present Present41 Coarctation 24 37 Present Present42 Coarctation 36 36 Present Present Present43 Coarctation 25 30 Present Present Present44 Coarctation 26 32 Present Present Present45 Coarctation 34 34 Present Present Present Present46 Coarctation 36 36 Present Present Present47 Coarctation 27 27 Present Present Present Present Present Present Present48 Coarctation 38 38 Present Present Present Present Present Present Present49 Coarctation 23 30 Present Present Present Present50 Coarctation 23 33 Present Present Present Present Present51 Coarctation 33 33 Present Present Present Present52 Coarctation 21 21 Present Present53 Coarctation 21 36 Present54 Coarctation 23 32 Present Present Present

Total 43 25 17 9 2 1 2 18 16 1 18 7 3 1 2 7 6 1Perent 80% 46% 31% 17% 4% 2% 4% 33% 30% 2% 33% 13% 6% 2% 4% 13% 11% 2%

Atrium

Number CLASSIFICATINGESTATIONAL

AGE (weeks) At First Examination

GESTATIONAL AGE (weeks) at

Last Examination

Prenatal RV/LV Area

Disproportion

Bicuspid Aortic Valve

Aortic Arch Hypoplasia

Aortic Valve Hypoplasia

Sub-Aortic Membrane

Dysplastic Aortic Valve

Unicuspid Aortic Valve

Ventricular Septal Defect

Mitral Valve Abnormality

Supravalvar Mtral Ring

Atrial Septal Defect

Left Superior Vena dava

Partial Anomalous Pulmonary

Venous Return

Right Sided Aortic Arch

Aberrant Right Subclavian

Artery

Common Brachiocephalic

Trunk

Coarctation Shelf

Isolated Left Pulmonary

Artery from Left Ductus Arteriosus

1 False-Positive 25 35 Present Present2 False-Positive 38 38 Present 13 False-Positive 32 37 Present Present Present4 False-Positive 30 30 Present 25 False-Positive 20 32 Present Present6 False-Positive 25 33 Present 37 False-Positive 32 33 Present 48 False-Positive 25 29 Present Present Present9 False-Positive 35 35 Present 5

10 False-Positive 33 33 611 False-Positive 28 28 Present Present Present12 False-Positive 36 36 Present 713 False-Positive 25 33 Present Present14 False-Positive 23 35 Present Present15 False-Positive 29 29 Present 816 False-Positive 36 36 Present Present Present17 False-Positive 35 35 Present 918 False-Positive 29 29 Present Present19 False-Positive 38 38 Present20 False-Positive 36 36 Present 1021 False-Positive 24 31 Present Present22 False-Positive 31 31 Present 1123 False-Positive 21 36 Present24 False-Positive 32 32 Present 1225 False-Positive 35 35 Present 1326 False-Positive 22 32 Present Present27 False-Positive 25 33 Present Present28 False-Positive 23 35 Present Present29 False-Positive 27 32 Present Present Present30 False-Positive 35 35 Present31 False-Positive 36 36 1432 False-Positive 37 37 Present Present Present33 False-Positive 37 37 Present Present34 False-Positive 21 29 1535 False-Positive 38 38 Present Present36 False-Positive 26 26 Present 1637 False-Positive 23 35 Present Present Present38 False-Positive 33 35 Present 1739 False-Positive 38 38 1840 False-Positive 38 38 Present Present Present41 False-Positive 31 31 Present Present Present42 False-Positive 21 34 Present Present Present43 False-Positive 21 34 1944 False-Positive 36 36 Present Present45 False-Positive 36 36 Present46 False-Positive 25 32 Present Present Present47 False-Positive 19 23 Present Present Present48 False-Positive 37 37 Present49 False-Positive 21 37 Present50 False-Positive 28 33 Present Present Present51 False-Positive 34 34 2052 False-Positive 21 37 Present 2153 False-Positive 23 36 Present Present Present54 False-Positive 35 35 Present Present Present Present

Total 41 12 6 4 0 1 6 2 0 5 4 0 0 0 9 0 0Perent 76% 22% 11% 7% 0% 2% 0% 11% 4% 0% 9% 7% 0% 0% 0% 17% 0% 0%

AORTA Ventricle Venous System Arch

AORTA Ventricle Venous System Arch

Associated Abnormal Cardiac Findings: True Coarctation

Associated Abnormal Cardiac Findings: Non-Coarctation

Logistic Regression Analysis

1. Size of the 4CV

2. Size and shape of the

RV and LV

3. Abnormal contractility of

the RV and LV

Logistic Regression Analysis

Sensitivity 96%

False-Positive Rate 4%

Specificity 96%

False-Negative Rate 4%

28 Variables

ROC AREA=0.98

Why Use This Analysis?

Assessment Using Speckle TrackingAnalysis Takes <5 Minutes

4-Chamber Analysis to MeasureThe Variables Described in

This Presentation is CommerciallyAvailable

Diagnosing Coarctation - A Clinical Dilemma-...odds ratio, 38.2; 95% confidence interval,...

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