Surgical Approach for Aortic Coarctation Influences Arterial Compliance and Blood Pressure Control

Transcription

1 Surgical Approach for Aortic Coarctation Influences Arterial Compliance and Blood Pressure Control Damien Kenny, MB, Jaimie W. Polson, PhD, Robin P. Martin, MB, Dirk G. Wilson, MB, Massimo Caputo, MD, John R. Cockcroft, MD, Julian F. R. Paton, PhD, and Andrew R. Wolf, MD Bristol Congenital Heart Centre and Department of Anaesthesia, Bristol Royal Hospital for Children, Bristol, United Kingdom; School of Medical Science, University of Sydney, Sydney, Australia; Department of Paediatric Cardiology, University Hospital Wales, and Department of Cardiology, Cardiff University, Cardiff, United Kingdom; and Department of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom Background. Increased arterial stiffness is linked to hypertension in adults after surgical repair for coarctation of the aorta. We evaluated the influence of surgical approaches, namely, subclavian flap repair (SFR) and end-to-end anastomosis (EEA), on arterial stiffness, blood pressure, cardiac output, and cardiac baroreceptor function in a cohort of young children after coarctation repair to determine if the surgical approach influenced longer term blood pressure control. Methods. We measured pulse wave velocity in 21 children with a mean age of 5 years, after early (less than 6 months) coarctation repair (SFR, n 11; EEA, n 10), and compared these with 18 matched controls. Blood pressure was recorded on three occasions from the right arm. Cardiac output was recorded using a transthoracic bioimpedence technique. We measured spontaneous baroreceptor reflex sensitivity to evaluate whether increased arterial stiffness was associated with reduced aortic baroreflex sensitivity. Results. Right arm systolic blood pressure ( mm Hg SFR versus mm Hg EEA, p 0.03) and pulse wave velocity ( ms 1 SFR versus ms 1 EEA, p 0.02) were significantly greater in the SFR compared with EEA group. Blood pressure and pulse wave velocity were also higher in the SFR group compared with controls. These differences were not demonstrated when comparing the EEA group with controls. There was no difference in stroke volume, spontaneous baroreceptor reflex sensitivity, or heart rate or blood pressure variability between the groups. Conclusions. Young children undergoing SFR have higher blood pressure and stiffer upper limb arteries compared with matched children undergoing EEA. Our data suggest that better longer-term cardiovascular outcome is to be expected with the EEA surgical approach. (Ann Thorac Surg 2010;90:600 4) 2010 by The Society of Thoracic Surgeons Accepted for publication April 27, Address correspondence to Dr Wolf, Paediatric Intensive Care and Cardiac Anaesthesia, Bristol Royal Hospital for Children, Upper Maudlin St, Bristol BS2 8HW, United Kingdom; awolfbch@aol.com. Currently, early surgical mortality after coarctation of the aorta (CoA) repair is negligible [1]. Premature systolic hypertension, however, leads to significant morbidity and is the most important outcome variable in patients with repaired CoA [2-6]. Earlier repair reduces the occurrence of subsequent hypertension [7, 8], but at least 20% of patients are hypertensive by adolescence, despite effective early surgical intervention [9]. An association between reduced upper limb arterial compliance and hypertension has been demonstrated in patients after CoA repair [10], and although the benefit of early repair on this relationship has been demonstrated [7], differences in outcome based on the type of surgical repair have been conflicting [11, 12]. Increased systolic blood pressure (BP) in older children undergoing subclavian flap repair (SFR) compared with end-to-end anastomosis (EEA) has been demonstrated [11, 13]; however, this has not been examined after neonatal repair. Furthermore, the relationship between the type of repair and established surrogates of arterial stiffness, along with cardiac output the two major determinants of systolic BP, has not been reported. We examined these variables in young children after early coarctation repair (both EEA and SFR) and compared these values to age-matched controls to determine if type of surgical repair influenced arterial compliance and subsequent systolic BP control. Although SFR is diminishing as a surgical approach for CoA, it is still supported [14], and its impact on longer term blood pressure control remains relevant to longer term followup. In addition, having shown previously that spontaneous baroreceptor reflex sensitivity (sbrs) is reduced preoperatively in neonates with coarctation [15], we wished to examine the long-term sbrs after several postoperative years and its possible relationship to the selected surgical repair. In particular, we hypothesized that while a relationship between baroreflex function and reduced arterial compliance in the pathogenesis of hypertension after coarctation repair has been suggested in adult coarctation patients [16], this correlation may not occur at an earlier age or with earlier repair by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg KENNY ET AL 2010;90:600 4 COARCTATION SURGERY AND BLOOD PRESSURE 601 Patients and Methods Fifty consecutive patients between 4 and 6 years of age undergoing early repair (less than 6 months) for CoA were retrospectively identified from surgical records in a single tertiary congenital cardiac center. During this time, the type of surgical repair selected (EEA versus SFR) was based on surgical preference of two congenital surgeons operating in our unit. Patients with associated complex congenital heart disease (n 14) were excluded. Patient notes were examined for further exclusion criteria, namely, birth weight less than 2 kg (due to reported effects of low birth weight on arterial compliance [17],n 2), reintervention for recurrent CoA (n 3), residual aortic obstruction (defined as continuous Doppler velocity greater than 2.5 m/s or diastolic extension on the Doppler trace; n 4), and antihypertensive medication (n 2). Of the remaining 25 patients invited on a voluntary basis to participate, we achieved parental agreement for 23. During the same time frame, we recruited 19 control children from members of staff working within our unit. Of the 23 CoA patients recruited, 2 were excluded at time of study owing to previously unidentified recoarctation (n 1) and severe intrauterine growth retardation (n 1). One control child was excluded because of previously undiagnosed hypertension and has since been referred for further investigation. Somerset Research Ethics Committee approval was granted for the study, and informed written consent was obtained from the parents of each child. Data Acquisition All patients were studied in a quiet room at standard room temperature. Blood pressure was measured on three separate occasions from the right arm with a validated automated oscillometric device (Dynamap PRO 300; Critikon, Tampa, FL) after a period of quiet rest as per international guidelines [18], and an average of these recordings was used in the calculations. Assessment of sbrs was carried out as previously reported [15]. Briefly, continuous BP waveform was recorded from the middle finger of the right hand (Portapres Systems; FMS, Amsterdam, Netherlands) and electrocardiography (ECG) recorded with a standard three-lead configuration. Analogue output signals of BP and ECG were displayed and stored on computer with Spike 2 software (Cambridge Electronic Design, Cambridge, England). Assessment of sbrs, heart rate variability, and blood pressure variability was carried out using a sequence technique. Pulse wave velocity (PWV) was measured in the right arm and right leg using a validated [19] pulse volume recording technique (Vicorder; Skidmore Medical, Bristol, UK) with an inflatable cuff placed proximally and distally on the limb of interest. The Vicorder continuously records oscillometric blood pressure waveform from the proximal and distal ends of the arterial segment under consideration at a sampling rate of 1,000 Hz. Autoanalysis is performed every 3 s, whereby the waveforms are double differentiated to identify the foot of each proximal and distal wave, and a cross correlation performed to identify the average Fig 1. Arterial pulse wave velocity as calculated by the Vicorder. The arterial waveforms from the proximal and distal vessel are simultaneously recorded and digitized at a sampling rate of 1.8 ms and displayed on the attached computer screen. Points A and B are then identified using a second differential on the rising portion of the waveform to identify the upstroke of each waveform. These points are then cross-correlated to provide an accurate measure of the time delay. Pulse wave velocity is calculated by dividing the distance the pulse wave has travelled on the limb by this time delay. phase shift (delay). Distance is measured between the two points, and velocity is calculated as distance divided by time (Fig 1). Measurements were made from the right arm and right leg over 90 s, and mean values were used in the calculations. Cardiac output was measured noninvasively using electrical velocimetry (ICON; Osypka Medical, Berlin, Germany), a transthoracic bioimpedence technique that detects changes in thoracic fluid shifts based on changes in transthoracic conductivity due to alignment of the erythrocytes during early systole. This technique has shown excellent correlation with direct Fick estimates of cardiac output in patients with congenital heart disease [20]. Statistical Analysis The investigators were blinded to the type of surgical repair during data collection and analysis. Data are expressed as mean SE unless otherwise stated. Data were tested for normality using a Shapiro-Wilk s test. Comparisons between the three groups were calculated using analysis of variance. Regression analysis was performed for PWV and systolic BP among the three groups, and comparison was made using an F-test. All p values less than 0.05 were considered to be statistically significant. All analyses were carried out using SPSS 14.0 (SPSS, Chicago, IL). Results Of 21 CoA patients studied, 11 had previous SFR and 10 EEA. The EEA patients had later surgical repair than SFR patients; however, this was not statistically significant

3 602 KENNY ET AL Ann Thorac Surg COARCTATION SURGERY AND BLOOD PRESSURE 2010;90:600 4 Table 1. Demographic Details and Comparative Data Between Subclavian Flap Repair (SFR), End-to-End Anastomosis (EEA), and Control Groups SFR EEA Controls Total number Sex, male Birth weight, kg Age at surgery, days Age at follow-up, years BSA at follow-up, kg m 2 Bicuspid aortic valve 8 8 SBP, mm Hg a,b DBP, mm Hg Arm PWV, ms a,b Leg PWV, ms Stroke index, ml m Cardiac index, L m sbrs, ms mm Hg a Indicates statistical significance (p 0.05) between SFR and EEA groups. b Indicates statistical significance between SFR and control groups. BSA body surface area; DBP diastolic blood pressure; PWV pulse wave velocity; SBP systolic blood pressure; sbrs spontaneous baroreceptor reflex sensitivity. (p 0.11). Demographic details of all subjects are outlined in Table 1. Right arm systolic BP was greater in the SFR group compared with the EEA group ( mm Hg versus mm Hg; p 0.03). The PWV from the right arm was also higher in the SFR group ( m/s versus m/s; p 0.02). Systolic BP and arm PWV were also higher in the SFR group than in the control group. In contrast, these variables were not different in the EEA group versus control group. There was no difference in lower limb PWV in any group. Diastolic BP was higher in the SFR group ( mm Hg) compared with the EEA group ( mm Hg, p 0.08) and the control group ( mm Hg, p 0.05). although this did not quite reach statistical significance. On regression analysis of upper limb PWV and systolic BP, there was a significant correlation between these variables (r 2 0.5, p 0.001; Fig 2). The relationship between PWV and systolic BP was constant among the three groups, with no significant difference in slope or r 2 value. There was no significant difference in stroke index (SFR ml/m 2 versus EEA ml/m 2 ; p 0.81) between the two types of surgery, and no difference when SFR and EAA groups were compared with controls. Similarly, sbrs was comparable between the EEA and SFR groups (SFR ms/mm Hg 1 versus EEA ms/mm Hg 1 ; p 0.32), and there was no difference between these values in the CoA group taken as a whole compared with the control group (CoA ms/mm Hg 1 versus control ms/mm Hg 1 ; p 0.59). Comment These data demonstrate higher systolic BP and increased PWV in the upper limb large arteries of patients undergoing SFR compared with EEA. This difference was also seen in the SFR group, but not in the EEA group, when compared with controls, indicating early and more effective improvement in blood pressure control and arterial compliance in EEA patients. Considering the impact of increased arterial stiffness on blood pressure control on these patients [21, 22], this finding is likely to have significant implications for longer term outcomes in patients undergoing early surgical repair of CoA. Development of arterial hypertension in a significant proportion of postcoarctectomy patients by adolescence, despite early repair, has been clearly demonstrated [9] and represents the major health management concern in this patient group [2, 4-6]. Postulated mechanisms for late postcoarctectomy hypertension include a widespread upper limb vasculopathy leading to increased arterial stiffness and baroreceptor reflex dysfunction due to exposure to abnormal blood pressure of the precoarcted baroreceptors in fetal and early neonatal life. Increased arterial stiffness has been demonstrated in neonates with CoA both before surgical repair and at 3-year follow-up [23, 24]. The association between increased arterial stiffness and systolic hypertension is well established [25], and increased arterial stiffness is an independent risk factor for mortality in adults with hypertension [26]. Reduced large artery compliance is of particular relevance to CoA because, along with stroke volume, it provides the main determinant of systolic BP [25], which is of primary concern in hypertensive patients after repair of CoA. However, although studies have demonstrated an association between systolic hypertension and increased arterial stiffness in patients with repaired CoA, particularly with regard to the timing of repair [7, 10], there are no reports on the relationship between surgical approach and arterial stiffness in young patients without Fig 2. Relationship between right arm pulse wave velocity (PWV) and systolic blood pressure (SBP) in all subjects. Overall regression line (y 10.12x 44.93, r ) is represented by thicker continuous line; control subjects are represented by triangles and a short dashed line (regression equation: y 10.63x 40.64, r ); SFR is represented by circles and longer dashed line (regression equation: y 8.02x 55.91, r ); and EEA is represented by squares and thin continuous line (regression equation: y 9.48x 51.13, r ).

4 Ann Thorac Surg KENNY ET AL 2010;90:600 4 COARCTATION SURGERY AND BLOOD PRESSURE 603 residual CoA after neonatal repair. Bassareo and colleagues [11] have demonstrated decreased QKd intervals in patients with SFR compared with EEA as an estimate of increased arterial rigidity in the SFR group. However, this technique is not an accepted correlate of large artery stiffness [27], and the authors included patients with later repair and recoarctation, which was more prevalent in the SFR group, thus acting as a confounding variable. Previous studies have reported on comparative trials of EEA versus SFR regarding survival, need for reintervention and aneurysm formation [28, 29]. However, the importance of these outcomes is diminishing because of improvements in percutaneous stenting technology. In contrast, incidence of hypertension, which is arguably the single most important outcome variable in these patients [4], has received little attention and potential mechanisms underlying these differences have not been examined. Several studies have suggested the possibility that altered arterial baroreceptor function may be a driving mechanism for hypertension in postcoarctectomy patients [16, 30], although it is unclear whether baroreceptor function was abnormal before hypertension in these studies. Sehested and coworkers [16] demonstrated reduced reactivity and increased collagen in the precoarctation aorta and postulated that this would allow the arterial baroreceptor to tolerate higher blood pressure due to reduced stretching. It is conceivable that different surgical approaches could have different effects on the arterial baroreceptors located in the aortic arch dependant on the extent of aortic resection or how far the incision lines extend into the aortic arch. That could result in different functioning of the baroreceptor reflex. However, our data showed no differences in sbrs between both types of surgical procedure and controls, suggesting that at least at this stage of development, baroreceptor function is not influenced by the surgical approach. Finally, neither stroke index nor cardiac index was statistically different between the groups, making an increase in cardiac output unlikely as the cause of increased systolic BP in the SFR group. The question arises as to how surgical approach may affect arterial compliance and systolic BP. One possibility is that increased upper limb arterial stiffness in the SFR group may reflect an ongoing regional effect of residual coarctation tissue on the upper limb arterial dynamics compared with the fully resected EEA approach. Abnormal flow dynamics have been shown to influence aortic remodeling in animal models of CoA [31], and it is possible that SFR could promote greater low velocity shear stress and subsequent inflammatory changes in the upper limb vasculature, which in turn could affect upper limb arterial compliance [32]. It is also conceivable that the left subclavian artery plays a role. Incorporation of this artery into the aorta and its subsequent dynamic functioning under nonphysiologic conditions may be contributory. Histologic studies have demonstrated the thickness of the media of the left subclavian artery is smaller than that of the aortic isthmus and descending aorta of the same patient [33]. Earlier reflected waves from the SFR site due to its different wall structure or due to a more diffuse scar site may lead to greater augmentation of central systolic BP and maintain abnormal arterial compliance through increased mechanical forces, whereas this may have subsided in EEA patients after repair. As this is somewhat speculative, further studies are under way to evaluate this hypothesis. In summary, these data show that even at 5 years of age, higher resting systolic BP and upper limb PWV are evident after early SFR but not EEA repair of CoA. These findings raise concerns about the adoption of the SFR surgical approach on arterial dynamics and blood pressure control in CoA patients, and the possibility that these differences lead to increased risk of hypertension in later life. Since hypertension is recognized as the most important long-term outcome variable in these patients, extensive efforts should be made to ensure that any factors leading to its increased prevalence are adequately addressed. A greater understanding of the mechanisms involved in the hypertensive response will also lead to earlier recognition and more targeted treatment strategies. We conclude that the EAA approach should be the preferred surgical approach for CoA repair as it appears to be free from subsequent cardiovascular pathology, at least until 5 years of age. Further studies may be required, in particular using magnetic resonance imaging, to compare in detail the effect of each surgical approach on the dynamic functioning of the aorta. Study Limitations This is a retrospective study on patients undergoing EEA or SFR chosen in a nonrandomized fashion. Surgery was performed based on preference of two individual surgeons in a single center, and unintentional bias in case selection cannot be ruled out. That said, each surgeon performed exclusively SFR or EEA and, therefore, type of surgical correction was based solely on which surgeon was operating when the diagnosis was made. The authors are aware of data relating morphology of the aortic arch to increased aortic stiffness index [34]; however, this was not assessed as magnetic resonance imaging would require general anesthesia for children of this age. Validation data on all methods assessing PWV is not present in children, and the Vicorder is no different. This is, however, a straightforward measurement tool based on measuring pulse transit time between two points on a large artery. This is an accepted measurement approach for assessing PWV [27]. The authors are aware that SFR is less commonly performed compared with EEA in the current surgical era; however, its overall prevalence in a lifelong condition requires careful blood pressure assessment in this group of patients. Lastly, patient numbers are limited; however, that is predominantly due to the strict exclusion criteria used so as to ensure those with potential confounding features were not included.

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