Melissa G.Y. Lee

Twenty-four-hour ambulatory blood pressure monitoring detects a high prevalence of hypertension late after coarctation repair in patients with hypoplastic arches.

OBJECTIVES To determine by 24-hour blood pressure monitoring the risk of hypertension late after coarctation repair in patients with arch hypoplasia. METHODS Sixty-two of 116 consecutive patients (age, ≥10 years) who had coarctation repair and were quoted subjectively by the surgeon or the cardiologist to have arch hypoplasia at the time of the repair underwent a transthoracic echocardiogram and 24-hour blood pressure monitoring. Median age at repair was 11 days (range, 6-48 days). Mean preoperative z score of the proximal transverse arch was -2.43 ± 0.46. Eight patients had a repair via sternotomy (6 end-to-side anastomoses, 2 patch repairs) and 54 had a conventional repair via thoracotomy. RESULTS After a follow-up of 18 ± 5 years, 27% of the patients (17/62) had resting hypertension and 60% (37/62) had abnormal ambulatory blood pressure. Sensitivity of high resting blood pressure in detecting an abnormal 24-hour ambulatory blood pressure was 41%. Twenty patients had arch obstruction at last follow-up. Eighteen of them (90%) had abnormal ambulatory blood pressure. None of the patients operated on with end-to-side repair via sternotomy had reobstruction compared with 33% (18/54) of those repaired via thoracotomy. CONCLUSIONS Patients with a hypoplastic arch operated via thoracotomy have an alarming prevalence of hypertension. Regular follow-up with 24-hour ambulatory blood pressure monitoring is warranted, especially in patients who have had a smaller aortic arch at the time of the initial operation.

Poor outcomes after surgery for coarctation repair with hypoplastic arch warrants more extensive initial surgery and close long-term follow-up

OBJECTIVES Late outcomes of repair of coarctation with arch hypoplasia have not yet been described. Hypertension and arch reobstruction frequently occur after standard coarctation repair and thus we sought to determine the long-term results of repair in the subset of patients with arch hypoplasia at a single institution over a 20-year period. METHODS We reviewed the files of the 305 consecutive patients quoted to have arch hypoplasia who had undergone a coarctation repair in a single institution between 1984 and 2004. Repair was performed through a sternotomy in 74 patients (24%), 58 of them undergoing a repair consisting of an end-to-side anastomosis. RESULTS Early mortality was 9% but there was only 1 death among patients without a major associated anomaly. Eight patients required reintervention before discharge due to residual obstruction. The follow-up was available in 96% of the patients. Only 45% of the patients over 15 years of age had cardiology review in the last 2 years. Survival at 10 and 20 years was 94% (95% CI: 91-97%) and 92% (95% CI: 86-95%), respectively. There were a total of 66 late reinterventions in 49 (18%) patients. Ten- and 20-year freedom from reintervention was 84% (95% CI: 78-88%) and 72% (95% CI: 63-80%), respectively. Ten- and 20-year freedom from reobstruction was 75% (95% CI: 69-80%) and 45% (95% CI: 34-55%), respectively. Patients undergoing end-to-side repair from sternotomy had less arch reobstruction than those undergoing extended end-to-end repair by thoracotomy (92 vs 61% freedom from reobstruction at 10 years, P < 0.001). Only 68% of the patients were normotensive at the last follow-up. Arch obstruction on echocardiogram was associated with an increased prevalence of hypertension (P = 0.018). CONCLUSIONS After coarctation repair, half of the patients with hypoplasia of the transverse arch will develop arch reobstruction and a third will become hypertensive. The technique of end-to-side repair performed through a sternotomy seems to alleviate these issues, and could be offered to a larger proportion of patients with hypoplasia of the aortic arch. Many of these patients are lost to follow-up during adolescence, at a time when ongoing care seems mandatory.

End-to-Side Repair for Aortic Arch Lesions Offers Excellent Chances to Reach Adulthood Without Reoperation

BACKGROUND The purpose of this study was to determine the rate of reinterventions from birth to adulthood after end-to-side anastomosis technique for interrupted and hypoplastic aortic arches. Multicenter data have shown that more than half of patients require arch reintervention in the 2 decades after repair. METHODS The follow-up of 170 consecutive patients undergoing end-to-side repair through sternotomy for interrupted aortic arch (95) or coarctation (75) in one institution between 1985 and 2012 was reviewed. Associated lesions included ventricular septal defect (143) and bicuspid aortic valve (50). One-stage repair was performed in 158 patients (93%). RESULTS There were 12 hospital deaths (7%), and 4 early arch reinterventions (2 for bronchial compression). Eleven hospital survivors (7%) were lost to follow-up. After a mean of 10 ± 6 years, there were 9 late deaths. Eighteen-year survival was 93% (95% confidence interval: 87 to 96). Eight patients had bronchial compression, 5 during initial stay and 3 after hospital discharge; 2 of them required surgery. Eighteen-year freedom from arch reoperation was 87% (95% confidence interval: 76 to 93). An additional 10 patients underwent balloon dilation, for an 18-year freedom from reintervention (balloon dilation or surgery) of 77% (95% confidence interval: 65 to 85). At last follow-up, 24 patients (16%) had an echocardiographic gradient greater than 25 mm Hg. Blood pressure was recorded in 105 patients, and only 11 (10%) were hypertensive. CONCLUSIONS The end-to-side anastomosis technique for repair of aortic arch lesions results in a low rate of mortality, arch reoperation, and late hypertension. The development of arch obstruction requiring balloon dilation warrants continuous follow-up of these patients.

Coarctation of the Aorta can no Longer be Considered a Benign Condition

the ratio between the diameter of the arch and thediameter of the ascending aorta as in the study by Tong et al[4]. The cut-off of 0.5 for a normal arch was derived from studies [8], while others have advanced on echocar- and magnetic resonance imaging (MRI) data that ratio should be above 0.9 [9]. Others have opted to thearch to descending aorta [10]. Whatever value chosen, arch hypoplasia has been repeatedly dem- to be predictive of adverse outcomes, and it is that hypoplasia of thearch should be defined as underwhichlatecomplicationswilloccur,butthisvalue not yet known. definition of arch reobstruction seems to be equally There isa general consensus that the arch if echocardiography demonstrates a pressure gra- through the coarctation repair site. Echocardiography to be far more sensitive in detecting arch obstruction clinicalgradient, and a study analyzing only willunderestimatetheprevalenceofarchobstruc- [10].ItisinterestingtonotethatPadangetal.usedaratio theactual diameter of residual coarctation segment to diameter ofthedescending aorta as definition [5].Whateverquantificationmethodforobstruc- ischosen likely to be of little value if the procured are not correlated to the only crucial clinical namely the development of hypertension. themostsensitivemethodtodetecthypertensionis use of 24-hour ambulatory blood pressure monitoring. should be aware that any studies, such as those pre- in this issue, using resting blood pressure measure- alone will underestimate the prevalence of [1,7]. In an ongoing investigation we have that, when screened by 24-hour ambulatory bloodKeywords Aortic arch Aortic arch hypoplasia Coarctation of the aorta Congenital heart defectHypertension Outcome studies

Elevated sympathetic activity, endothelial dysfunction, and late hypertension after repair of coarctation of the aorta

BACKGROUND There is a high prevalence of late hypertension after coarctation repair. The relative contribution of elevated sympathetic tone and endothelial dysfunction to its development is unknown. This study aims to investigate the neural profile of coarctation patients including muscle sympathetic nerve activity testing to directly measure sympathetic nervous activity. METHODS Twenty-three patients aged ≥18years with a coarctation repair underwent measurements of clinic and 24-h blood pressures, muscle sympathetic nerve activity, sympathetic and cardiac baroreflex functions, digital endothelial function, and ambulatory arterial stiffness index. Median age at repair was 1.2months (interquartile range: 0-9months). Patients were compared to 17 healthy matched controls. RESULTS After 26±5years, 6% (1/18) and 44% (8/18) suffered clinic hypertension and prehypertension, respectively. On 24-h blood pressure monitoring, 15% (3/20) and 20% (4/20) had hypertension and prehypertension, respectively. Coarctation patients had elevated muscle sympathetic nerve activity compared with controls (49.6±24.9 vs. 29.9±14.0 bursts/100 heartbeats, p=0.02), dampened sympathetic baroreflex function (-2.2±2.1 vs. -7.0±5.6 bursts/100heartbeats·mm·Hg-1, p=0.007), normal cardiac baroreflex function (41.9±30.4 vs. 35.7±21.1ms·mm·Hg-1, p=0.6), endothelial dysfunction (pulse amplitude tonometry ratio: 0.39±0.32 vs. 0.81±0.50, p=0.004), and increased ambulatory arterial stiffness index (0.46±0.15 vs. 0.29±0.17, p=0.008). CONCLUSION After coarctation repair patients have increased muscle sympathetic nerve activity, dampened sympathetic baroreflex response, endothelial dysfunction, and increased ambulatory arterial stiffness index, all of which may contribute to the development of late hypertension.

Complications of Extra-Anatomic Aortic Bypass for Complex Coarctation and Aortic Arch Hypoplasia

BACKGROUND We have adopted the extra-anatomic bypass graft as the procedure of choice for the treatment of coarctation and aortic arch hypoplasia in the adult-sized patient. However, we have experienced prolonged chest drainage and have decided to investigate this complication and the morbidity related to this procedure. METHODS Between 1996 and 2010, 15 extra-anatomic bypass grafts of the aorta were performed in 14 patients. Their hospital records and follow-up data were retrospectively reviewed and compared with those of 14 consecutive patients operated with other conventional techniques over the same time period. RESULTS There was no hospital mortality. After the extra-anatomic bypass procedure, patients had longer hospital stay because of prolonged pleural effusions. Four patients developed complications related to persistent effusions leading to reinterventions, which led to mediastinitis in 2 instances. At last follow-up, 2 of 14 patients with extra-anatomic bypass remained hypertensive, while 8 of the 14 patients who underwent other types of repair had arch obstruction, were hypertensive, or both. CONCLUSIONS In the adult-sized patient extra-anatomic bypass of the aortic arch relieves arch obstruction more effectively than conventional techniques. However, this technique is fraught with complications related to prolonged effusion drainage that may lead to mediastinitis and reintervention. Its indication should be weighted carefully.

Impact of arch reobstruction and early hypertension on late hypertension after coarctation repair

OBJECTIVES Late hypertension after coarctation repair is associated with high mortality, but its risk factors remain unclear. This study aims to determine early and late postoperative risk factors for late hypertension after coarctation repair. METHODS A cross-sectional study including transthoracic echocardiogram and 24-h blood pressure (BP) monitoring was performed in 144 patients aged ≥10 years with previous coarctation repair. Median age at repair was 39 days (interquartile range 0-3 years). Early postoperative hypertension was evaluated by calculating the mean of BP measurements taken on the same day before hospital discharge or the need for antihypertensives prior to discharge. Multivariable analyses were performed to adjust for gender, surgical age, and follow-up age. RESULTS After a mean follow-up period of 22 ± 7 years, 59% (84/142) of patients were hypertensive: 58% (82/142) on 24-h BP monitoring and 1% (2/142) on antihypertensives. Early postoperative hypertension was present in 58% (73/126): 39% (49/126) on BP measurements and 19% (24/126) on antihypertensives. Early and late arch reobstruction (transthoracic echocardiogram peak gradient ≥25 mmHg) was present in 37% (23/62) and 23% (33/144), respectively. On multivariable logistic analysis, early postoperative hypertension and maximum descending arch velocity on echocardiography were associated with late hypertension on 24-h BP monitoring (odds ratio 2.21, 95% confidence interval 1.05-4.66, P = 0.04; and odds ratio 2.28, 95% confidence interval 1.08-4.81, P = 0.03; respectively). CONCLUSIONS There is a high prevalence of late hypertension after coarctation repair. Arch reobstruction may be a major determinant of late hypertension. Early postoperative hypertension may identify very early in life those at risk of developing late hypertension.

Laryngeal ultrasound detects a high incidence of vocal cord paresis after aortic arch repair in neonates and young children

Objectives: To determine the incidence of vocal cord paresis (VCP) after neonatal aortic arch repair/Norwood‐type procedure, and the effectiveness of noninvasive laryngeal ultrasound in detecting VCP compared with gold standard invasive nasoendoscopy. Methods: Fifty‐two patients who underwent an arch repair (39 of 52; 75%) or Norwood‐type procedure (13 of 52; 25%) via sternotomy between April 1, 2015, and April 30, 2017 underwent laryngeal ultrasound (50 of 52; 96%) and/or flexible fiber optic nasoendoscopy (39 of 52; 75%) at 48 to 72 hours after endotracheal extubation. Primary arch diagnoses were coarctation in 56% (29 of 52), hypoplastic left heart syndrome in 17% (9 of 52), isolated hypoplastic arch in 17% (9 of 52), and interrupted aortic arch in 10% (5 of 52). The median patient age at surgery was 5.5 days (interquartile range, 4.0–12.5 days). Fifteen patients (15 of 52; 29%) required preoperative intubation. Results: Left VCP was present in 59% (23 of 39) of patients on nasoendoscopy and in 59% (27 of 46) of patients on laryngeal ultrasound, and 4 additional patients had inconclusive ultrasound results. There was agreement between the results of nasoendoscopy and conclusive ultrasound in all cases. The overall sensitivity, specificity, positive and negative predictive values, and Cohens kappa coefficient of laryngeal ultrasound compared with nasoendoscopy for the detection of left VCP were 95%, 88%, 91%, 93%, and 0.83, respectively. On multivariable analysis, preoperative intubation and arch repair techniques other than the Norwood procedure were associated with left VCP (odds ratio, 12.7; P = .03; and 14.1; P = .03, respectively). Conclusions: There is a high incidence of VCP after arch repair via sternotomy. Laryngeal ultrasound seems to be an effective and noninvasive method for detecting VCP in neonates and young children.

Identifying low-grade cellular rejection after heart transplantation in children by using gene expression profiling

Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection after heart transplantation but is costly and invasive. This study aims to distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart transplantation in children by using global gene expression profiling in blood. A total of 106 blood samples with corresponding EMB from 18 children who underwent heart transplantation from 2011 to 2014 were analyzed (18 baseline/pretransplantation samples, 88 EMB samples). Corresponding rejection grades for each blood sample were 0R in 39% (34/88), 1R in 51% (45/88), and 2R in 10% (9/88). mRNA from each sample was sequenced. Differential expression analysis was performed at the gene level. A k-nearest neighbor (kNN) analysis was applied to the most differentially expressed (DE) genes to identify rejection after transplantation. Mean age at transplantation was 10.0 ± 5.4 yr. Expression of B cell and T cell receptor sequences was used to measure the effect of posttransplantation immunosuppression. Follow-up samples had lower levels of immunoglobulin gene families compared with pretransplantation ( P < 3E-5) (lower numbers of activated B cells). T cell receptor alpha and beta gene families had decreased expression in 0R samples compared with pretransplantation ( P < 4E-5) but recovered to near baseline levels in 1R/2R samples. kNN using the most DE gene (MKS1) and k = 9 nearest neighbors correctly identified 83% (73/88) of 1R/2R compared with 0R by leave-one-out cross validation. Using a genomic approach we can distinguish low-grade cellular allograft rejection (1R/2R) from no rejection (0R) after heart transplantation in children despite a wide age range.

Are more extensive procedures warranted at the time of aortic arch reoperation

OBJECTIVES To determine the early and late outcomes of patients undergoing aortic arch reoperations. METHODS The follow-up of 70 patients undergoing a second arch operation (excluding univentricular physiology) between 1979 and 2015 was reviewed. Median age at initial arch operation and second operation was 9 days (interquartile range: 5-35) and 10 months (interquartile range: 3-64), respectively. The most common indication for initial arch operation was coarctation in 79% (55/70). The most common indication for a second arch operation was arch reobstruction in 90% (63/70). RESULTS There were 2 hospital deaths (2/70, 3%) and 3 early third arch operations (3/70, 4%). Late follow-up was available in 94% (64/68) of hospital survivors. After a mean of 9 ± 7 years, there were 5 late deaths (5/64, 8%). Fifteen-year survival was 90% (95% confidence interval: 75-96). Arch reobstruction (echocardiogram gradient >25 mmHg/third operation for reobstruction) was present in 28% (18/64) and 16% (10/64) required a third arch operation. Fifteen-year freedom from arch reobstruction and third arch operation was 63% (95% confidence interval: 43-78) and 74% (95% confidence interval: 52-87), respectively. On multivariable analysis, hypoplastic arch at initial arch repair (P = 0.03) and interposition graft at second arch operation (P < 0.0001) were risk factors for third arch operation. CONCLUSIONS Patients undergoing a second arch operation have significant rates of arch reobstruction and reoperation. The high rates of arch reobstruction and third arch operation warrant more extensive procedures at the time of second arch operation, especially in patients with a hypoplastic arch. Regular long-term monitoring after arch reoperation is mandatory.