Recovery of Biventricular Function After Catheter Intervention or Surgery for Neonatal Coarctation of the Aorta

Background Critical coarctation of the aorta (CoA) is a life-threatening condition in newborns that is associated with biventricular dysfunction. Objectives The purpose of this study was to examine clinical outcome and echocardiographic changes in isthmus diameter and biventricular function in newborns with critical CoA treated with balloon dilation/stent placement or surgery. Methods This is a retrospective single-center cohort study of 26 consecutive neonates with isolated critical CoA, who underwent transcatheter intervention (balloon angioplasty/stent; n = 10) or surgical CoA-repair (n = 16) (2012-2021). Isthmus dimensions and biventricular function at baseline and at hospital discharge were examined by echocardiography, including strain analysis of systolic and diastolic function using 2-dimensional speckle tracking. Results Cardiogenic shock at hospital admission was more frequent in the interventional vs the surgical cohort (50% vs 25% of neonates). Echocardiographic isthmus diameter increased with therapy by 0.9 ± 0.1 mm and 1.0 ± 0.1 mm, respectively. Severe systolic left ventricular (LV) dysfunction was more common in interventional patients pre-therapy (LV ejection fraction <50% in 90% vs 38% of surgical patients), resulting in strongly reduced longitudinal strain (LV: −12.3% vs −16.3%; right ventricle:−13.8% vs −16.1% in the interventional and surgical patients, respectively). Prior to hospital discharge, all 26 patients had full recovery of biventricular systolic function, including normalization of longitudinal, radial, and circumferential LV strain and longitudinal right ventricular free wall strain. Improvement of LV diastolic function by strain analysis was evident in both cohorts pre-hospital discharge. Conclusions Initial treatment of isolated CoA by percutaneous transcatheter intervention or surgical repair results in recovery of biventricular systolic function, making transcatheter treatment particularly suitable as rescue therapy for neonates with critical CoA.


INTRODUCTION
Coarctation of the aorta (CoA) is a common congenital obstructive anomaly of the aortic arch, defined as a juxtaductal narrowing of the aortic isthmus.It affects 4 per 10,000 births and accounts for 5-8% of all congenital heart diseases 1,2 .There is considerable variation in the severity of the coarctation and associated congenital heart defects such as atrial and ventricular septal defects or cardiovascular lesions such as aortic arch hypoplasia, bicuspid aortic valve (BAV) or patent ductus arteriosus (PDA) 3,4 .
Critical CoA typically manifests in neonates after a sudden constriction or closure of the ductus arteriosus and is characterized by an imminent or actual cardiogenic shock.The severity of cardiovascular decompensation and clinical manifestation depends on the rapidity of closure of the PDA, the diameter of the isthmus and the time of occurrence postnatally.While some neonates present with tachypnea, increased respiratory effort, restlessness, irritability, excessive perspiration and feeding poorly, others deteriorate rather rapidly.They may exhibit progressive respiratory distress, tachycardia and weak to absent femoral pulses as a symptom of systemic hypoperfusion 5 .In order to re-open or vasodilate the PDA, thus securing systemic blood flow, prostaglandin (PGE1) is often administered via continuous intravenous infusion, in addition to ICU measures such as inotropic support and correction of acidosis 6 .
Once patients are clinically stable, they undergo surgical repair of the CoA as the current gold standard in CoA treatment [7][8][9] .Transcatheter balloon dilation of the CoA ± stent placement are not routinely performed in neonates because of relatively high rates of restenosis and local complications such as femoral arterial injury and aneurysms [10][11][12] .There are, however, few reports on favorable outcomes in neonates with isolated coarctation presenting with cardiogenic shock/ severe left ventricular dysfunction who underwent emergency surgical therapy 13 .Other studies suggest that surgery unequivocally yields better intermediate and midterm results in neonates 8,9 7. Speckle tracking echocardiography and left and right ventricular strain analysis .In order to detect earlier and more modest impairment of myocardial contractility, we performed 2D speckle tracking analysis.We report recovery of biventricular function in both cohorts as observed in LV and RV myocardial strain variables (A,B,C,D).Graphs in the first and second column illustrate variable progression during hospital stay.The scatter dots plots in the third column illustrate the mean with the 95% confidence interval for the mean.Green and orange dots represent individual interventional and surgical patients, respectively.Abbreviations: LV, left ventricle; LVCS, LV circumferential strain; LVRS, LV radial strain; LV4CLS LV four chamber longitudinal strain; pre-Int, pre Intervention; post-Int, post Intervention; pre-OP, pre-operation; post-OP, post-operation; RV, right ventricle; RVFWLS, RV free wall longitudinal strain.
Supplemental Figure 8. Improvement of LV diastolic strain variables post-CoA therapy Patients in both cohorts reached similar diastolic strain values post CoA-treatment.The plots illustrate changes in peak diastolic radial (A) and circumferential strain rates (B) as well as improvement in LV peak diastolic radial velocity (C).Graphs in the first and second column illustrate variable progression during hospital stay.The scatter dots plots in the third column illustrate the mean with the 95% confidence interval for the mean.Green dots represent interventional and orange dots represent surgical patients.Abbreviations:LV, left ventricle; LVCSr, LV circumferential strain rate; LVPRD, LV peak radial displacement; LVPRV, LV peak radial velocity; LVRSr, LV radial strain rate; pre-Int, pre Intervention; post-Int, post Intervention; pre-OP, pre-operation; post-OP, post-operation.

Supplemental Figure 2 .Supplemental Figure 3 .Supplemental Figure 4 .Supplemental Figure 5 .Supplemental Figure 6 .
Representative examples of LV longitudinal strain analysis pre-and post-therapy This figure shows representative echocardiographic strain images and improvement of left ventricular longitudinal strain post-intervention (A) and post-surgery (B).The region of interest, in this case the LV, was divided into six segments and the TomTec 2D CPA (2D Cardiac Performance Analysis, TomTec Imaging systems, Unterschleissheim, Germany) extracts peak systolic values, symbolized by the dots in the strain curves.Low intraobserver variability in strain variables plots for strain variables; the lines represent the average differences and lower and higher confidence intervals.Single dots represent strain values of individual patients (both rounds of measurements).(A) LV Longitudinal Strain: Average Difference= 0.17, Lower CI= -3.43, Higher CI= 3.77; ICC = 0.913, 95%CI [0.854, 0.949], excellent reliability (B) LV Radial Strain: Average Difference=-1.71 , Lower CI=-8.34,Higher CI= 4.92; ICC=0.898,95%CI [0.786, 0.948], good reliability (C) LV Circumferential Strain: Average Difference= -0.66, Lower CI= -5.10, Higher CI=3.78;ICC=0.906,95%CI [0.838, 0.945], excellent reliability (D) RV Free Wall Longitudinal Strain: Average Difference= 0,48, Lower CI= -3,20, Higher CI= 4.17 ICC=0.89,95%CI [0.814, 0.935], good reliability Abbreviations: CI, confidence interval; ICC, intraclass correlation coefficient; LV, left ventricle; RV, right ventricle C Correlations of pressure gradients with PDA/Aortic isthmus diameter and LVEF NIBPGs between the right upper and lower extremity and PG max do not correlate with isthmus and PDA size(A-D).NIBPGs correlates more strongly with left ventricular performance than PG max, independently of isthmus diameter (E,F).Of note, some patients with poor LVEF (<50%) have lower PG max despite narrower CoA, suggesting decreasing magnitude of the pressure gradient with LV dysfunction or low cardiac output.In panels E and F dot size correlates with the isthmus diameter, smaller dots symbolizing isthmus diameter <2mm and bigger dots representing patients with isthmus diameters between 2 and 2.5mm.Green dots represent individual interventional patients and orange dots depict individual surgical patients.Abbreviations: LVEF, left ventricular ejection fraction; Non-invasive systolic blood pressure gradient between the right upper and lower extremity, systolic non-invasive blood pressure gradient; PDA, patent ductus arteriosus; PG max, maximal pressure gradient across the aortic isthmus in CW Doppler.Additional echocardiographic characterization of isthmus changes and left ventricular performanceThe plots show similar changes at CoA-site in both cohorts regarding isthmus dimensions and the maximal pressure gradient across the aortic isthmus (A,B).Change in the aortic valve-velocity time integral was statistically significant in the interventional cohort and varied greatly in surgical patients pre-and postoperatively (C).Graphs in the first and second column illustrate parameter progression during hospital stay.The box and whisker plots in the third column show the median, interquartile range and 10th and 90th percentile.The scatter dot plots in the fourth column illustrate the mean with the 95% confidence interval for the mean.Green dots represent individual interventional patients and orange dots represent individual surgical patients.Student's t-test was performed on parametric data and Wilcoxon paired two-tailed t-test on non-parametric data.P-Values < 0.05 were considered significant.Abbreviations: AoV VTI, aortic valve velocity time integral; PG Isthmus, maximal pressure gradient across the aortic isthmus in CW Doppler; pre-Int, pre Intervention; post-Int, post Intervention; pre-OP, pre-operation; post-OP, post-operation.Improvement of echocardiographic variables post-CoA treatment

Table 1 .
. Individual patient and procedure characteristics in the interventional cohort.

Table 2 .
Advanced echocardiography and strain analysis.All patients (n=26) received advanced echocardiographic examination pre-and post-therapy, at hospital admission and shortly before hospital discharge respectively, with echo-to-echo intervals of 10±6 days for the interventional patients and 11±4 days for the surgical patients.*Relative wall thickness was determined as the twofold of the left ventricular posterior wall thickness divided by left ventricular end-diastolic diameter.All measurements are presented as mean ± SD and SEM in parenthesis below.A t-test and Wilcoxon's signed-rank test were applied for parametric and non-parametric data respectively.Abbreviations: AoV VTI, aortic valve velocity time integral; FAC, fractional area change; FS, fractional shortening; IVSD/LVPWD, interventricular septal thickness-to-left ventricular posterior wall thickness ratio; LV, left ventricle; LVCS, LV circumferential strain; LVCSr, LV circumferential strain rate; LVEDD, LV end-diastolic diameter; LVEF, LV ejection fraction; LVPRD, LV peak radial displacement; LVPRV, LV peak radial velocity; LVRS, LV radial strain; LVRSr, LV radial strain rate; LV4CLS LV 4 chamber longitudinal strain; PSAX, parasternal short axis; RV, right ventricle; RVAWD, RV anterior wall thickness at end diastole; RVEDD, RV end-diastolic diameter; RVFWLS, RV free wall longitudinal strain; RWT, relative wall thickness; v max, maximal velocity.Supplemental

Table 3 .
Clinical course and echocardiographic status in infants of the interventional cohort.
PG max, peak pressure gradient across the isthmus measured in CW Doppler; RV, right ventricle; RVFWLS, RV free wall longitudinal strain; v max, maximal velocity.