Intraoperative surgical strategy changes in patients with chronic and end-stage renal disease undergoing coronary artery bypass grafting

Abstract

 

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OBJECTIVES

Factors such as more diffuse atherosclerosis, plaque instability and accelerated vascular calcification in patients with chronic and end-stage renal disease (ESRD) can potentially present intraoperative challenges in coronary artery bypass grafting (CABG) procedures. We evaluated whether patients with chronic and ESRD experienced more surgical strategy changes and/or graft revisions than patients with normal renal function when undergoing CABG procedures according to a protocol for intraoperative high-frequency ultrasound and transit-time flow measurement (TTFM).

METHODS

Outcomes of CABG for patients with chronic and ESRD and patients with normal renal function enrolled in the multicentre prospective REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study were compared retrospectively. The primary end point was frequency of intraoperative surgical strategy changes. The secondary end point was post-protamine TTFM parameters.

RESULTS

There were 95 patients with chronic and ESRD and 921 patients with normal renal function. Patients with chronic and ESRD undergoing CABG according to a protocol for intraoperative high-frequency ultrasound and TTFM had a higher rate of strategy changes overall [33.7% vs 24.3%; odds ratio (OR) = 1.58; 95% confidence interval (CI) = 1.01–2.48; P = 0.047] and greater revisions per graft (7.0% vs 3.4%; odds ratio = 2.14; 95% CI = 1.17–3.71; P = 0.008) compared to patients with normal renal function. Final post-protamine graft TTFM parameters were comparable between cohorts.

CONCLUSIONS

Patients with chronic and ESRD undergoing CABG procedures with high-frequency ultrasound and TTFM experience more surgical strategy changes than patients with normal renal function while achieving comparable graft flow.

Clinical trial registration number

ClinicalTrials.gov NCT02385344

INTRODUCTION

Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have nearly twice the rate of cardiovascular disease as patients with normal renal function [1]. An increased prevalence of traditional cardiovascular risk factors and nontraditional uraemia-related risk factors predispose this population to a greater likelihood of developing coronary artery disease (CAD), of more advanced CAD at first presentation and of worse cardiovascular disease-related outcomes than patients with normal renal function [2, 3]. Previous retrospective studies have shown that patients with CKD and multivessel CAD derive survival benefit from myocardial revascularization over medical therapy [4–6]. The evidence also suggests that coronary artery bypass grafting (CABG) is superior to percutaneous coronary intervention, particularly for patients with more advanced renal dysfunction [5, 7–10]. Although the 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines on Myocardial Revascularization recommended CABG for patients with CKD with multivessel disease and acceptable risk profiles, revascularization has been underutilized in this population, certainly owing in part to concerns about procedural risk and worse perioperative and long-term outcomes versus patients with normal renal function [4, 6, 11].

Many of the same risk factors accounting for the excess burden of cardiovascular disease in patients with CKD/ESRD also potentially present surgical challenges that could contribute to worse operative outcomes. For instance, CKD/ESRD is associated with more diffuse atherosclerotic disease, complex lesions, multivessel disease and plaque instability [2, 3, 12]. Lack of coronary collateralization and smaller vessel diameter limits sites for potential distal anastomotic targets [4, 13]. Additionally, CKD/ESRD is associated with a state of positive calcium balance and accelerated vascular calcification [2, 3, 14], which can impact intraoperative conduct by limiting potential areas of aortic clamping and distal anastomotic targets [15]. Coronary arteries with this morphological profile are more likely to have poor run-off contributing to graft failure [16]. Many of these lesions are difficult to assess and navigate intraoperatively with visual/tactile inspection alone, which is the conventional means of graft assessment during CABG [17]. Combined epicardial/epiaortic high-frequency ultrasound (HFUS) and transit-time flow measurement (TTFM) afford objective morphological and functional interrogation of potential aortic cross-clamp and proximal anastomosis sites, conduits and target sites, as well as completed bypass grafts, which can aid surgeons in navigating complex anatomical lesions and verifying adequate graft construction [18].

We evaluated whether the CKD/ESRD population, known to have more complex coronary lesions, experienced greater rates of surgical strategy changes and graft revisions than patients with normal renal function when undergoing CABG according to an intraoperative HFUS/TTFM protocol. Moreover, we evaluated if, due to their vascular morphology, patients with CKD/ESRD were more prone to graft dysfunction due to poor outflow, which could manifest perioperatively as inferior graft TTFM measurements compared to patients with normal renal function.

PATIENTS AND METHODS

Ethical statement

This study is a subanalysis of the previously published REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study [19]. Institutional review boards at each participating centre approved the trial, and all participants provided written, informed consent (Washington DC VA Medical Center IRB #01731; initial approval date 13 April 2015). The study was conducted in accordance with the principles of the Declaration of Helsinki. The REQUEST study was funded by Medistim ASA (Oslo, Norway). Principal investigators and authors had complete scientific freedom.

REgistry for QUality assESsmenT with ultrasound imaging and TTFM in cardiac bypass surgery study

The REQUEST study was an international, multicentre, prospective observational registry designed to capture information on changes to preoperatively proposed surgical plans during CABG based on intraoperative assessment with HFUS and TTFM performed using (MiraQ) or (VeriQ C) devices (Medistim ASA, Oslo, Norway). Patients undergoing isolated CABG for ≥ 2-vessel CAD were enrolled. Exclusion criteria included emergency cases, concomitant surgical procedures and comorbid muscle disorders or psychological, developmental or emotional disorders.

All participating surgeons (n = 36) had performed >20 CABG cases with HFUS/TTFM. Surgeons and study coordinators were trained to use and interpret HFUS/TTFM results according to a structured study protocol. Preoperatively, surgeons formulated surgical plans using coronary angiography and other discretionary imaging modalities (e.g. computed tomography), which included proposed aortic cannulation, cross-clamp and proximal anastomosis sites, bypass conduits, number of anastomoses and coronary targets. Plans were later compared with actual operative conduct to determine occurrence of strategy changes. Protocol steps included HFUS assessment of (i) ascending aorta; (ii) in situ conduit arteries; (iii) location of anastomotic sites; and (iv) anatomy/flow in completed anastomoses/grafts. TTFM assessment was recommended at a mean arterial pressure of 80 mm mercury. Parameters prompting re-evaluation of completed grafts for possible revision typically included (i) low mean graft flow: arterial grafts <15 ml/min and venous grafts <20 ml/min; (ii) increased pulsatility index >5; (iii) decreased diastolic filling (<70% for left-sided and <50% for right-sided coronary vessels). Changes in plan and/or revisions were performed at the surgeon’s discretion. Adherence to the HFUS/TTFM assessment protocol was highly recommended but was not mandatory. Surgeons provided detailed comments regarding any surgical changes performed including location and reason.

Study population

Between April 2015 and December 2017, a total of 1046 patients undergoing isolated CABG for multivessel CAD at 7 centres in Europe and North America were enrolled in the REQUEST study. Thirty patients were excluded due to screening failure (n = 8), lack of training of all surgical team members according to the REQUEST study protocol (n = 11) or unavailability of HFUS/TTFM images for analysis (n = 11). All 1016 patients meeting inclusion criteria for the REQUEST study were included in the current study. Patients were stratified into 2 cohorts based on the presence or absence of a documented medical diagnosis indicating either CKD, ESRD or receipt of renal allograft for ESRD.

Variables and outcome measures

Baseline patient and procedural characteristics, details of surgical changes, post-protamine TTFM parameters of completed grafts and in-hospital adverse events were collected prospectively. The primary outcome was frequency of intraoperative surgical strategy changes. The secondary outcome was post-protamine TTFM parameters.

Surgical strategy changes: definitions

Strategy changes were defined as any alterations from the preoperative plan. These changes could be based primarily on HFUS/TTFM use or visual/tactile inspection. Changes related to the aorta included changes to the cannulation site, cross-clamp site or site for proximal anastomosis. Changes regarding in situ conduits occurred if an alternative conduit was used. Changes to coronary targets included different locations of anastomoses due to calcification or insufficient calibre, detection of intramural vessels or need for endarterectomy. Changes to completed grafts were defined as primary anastomotic revision (i.e. revision of the proximal and/or distal anastomosis due to technical problems), secondary anastomotic revision (revision of the proximal or distal anastomosis due to graft kinking or inadequate length but not an issue with the anastomosis itself), primary conduit revision (without revision of either proximal/distal anastomosis) or the need for additional grafts (Supplementary Material, Table S1).

Statistical analyses

Preoperative demographic and clinical variables, procedure variables and incidence of surgical changes were compared between cohorts using the χ² and the independent samples t-test for categorical and continuous variables, respectively. The Fisher’s exact test was used in place of the χ² test when >25% of expected cell counts were <5. Normality was assessed using the Kolmogorov–Smirnov test. The Kruskal–Wallis test was used in place of the t-test if the continuous variable distribution was nonparametric. Incidence of surgical changes were presented as odds ratios (ORs) with 95% confidence intervals (CIs) from corresponding logistic regression models.

Kruskal–Wallis tests were used to examine associations between CKD/ESRD diagnosis and TTFM parameters within graft types (defined by combinations of conduit type and target artery territory). Only single conduits to single coronary targets were considered for analysis (i.e. sequential and Y- or T-grafts were not analysed). Grafts with less than 75% of TTFM parameters recorded and available for review were excluded from this portion of the analysis. Moreover, given that diastolic filling percentage data were missing in 25.1% of grafts, we did not analyse or report data for diastolic filling. Further, where there were fewer than 5 grafts of a given type contributed by either cohort, we did not analyse or report data for that graft type. Grafts with an acoustic coupling index <30% (indicating potential inaccuracy of ultrasound conductivity) were excluded. For graft types where individual patients contributed more than 1 graft, we performed a nested Kruskal–Wallis permutation test comparing the grafts of patients with CKD/ESRD to the grafts of patients with normal renal function (this only occurred for saphenous vein graft to circumflex artery system and saphenous vein graft to right coronary artery system combinations, for 12 patients total) [20]. All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA); P-value of <0.05 was considered statistically significant.

RESULTS

Patient demographics and comorbidities

There were 95 (9.4%) patients with CKD/ESRD and 921 (90.6%) with normal renal function. Patients with CKD/ESRD were more likely to have had a prior stroke (11.6% vs 5.5%; P = 0.019), hypertension (84.2% vs 69.9%; P = 0.003), diabetes (52.6% vs 38.2%; P = 0.006), chronic obstructive pulmonary disease (15.8% vs 6.7%; P = 0.002), peripheral vascular disease (16.8% vs 8.9%; P = 0.013) and a severely reduced left ventricular ejection fraction (8.7% vs 1.8%; P = 0.001). There were no differences between cohorts in severity of Canadian Cardiovascular Society angina classification, New York Heart Association functional classification of heart failure or left main disease (Table 1).

Operative variables

There was a trend towards patients with CKD/ESRD undergoing off-pump CABG more frequently than patients with normal renal function (48.4% vs 38.7%; P = 0.064) (Table 2). Bilateral internal thoracic artery use (20.0% vs 31.6%; P = 0.019) and multiarterial grafts (33.7% vs 44.2%; P = 0.049) were less common in the CKD/ESRD cohort. There was no difference in operative time (258 ± 93 min vs 257 ± 87 min; P = 0.86) or complete arterial revascularization (27.4% vs 26.0%; P = 0.76) between cohorts. Supplementary Material, Table S2 shows rates of HFUS/TTFM utilization.

Primary end points: changes in surgical strategy

Patients with CKD/ESRD had significantly more strategy changes overall (33.7% vs 24.3%; OR = 1.58; 95% CI = 1.01–2.48; P = 0.047) and changes due to visual/tactile inspection (10.5% vs 3.7%; OR = 3.08; 95% CI = 1.47–6.43; P = 0.003) compared to patients with normal renal function (Table 3; Fig. 1). Compared to patients with normal renal function, patients with CKD/ESRD also had greater changes numerically due to HFUS/TTFM assessment (26.3% vs 18.7%; OR = 1.56; 95% CI = 0.96–2.53; P = 0.075), though this finding was trend-level only. On a per graft basis, patients with CKD/ESRD also had more graft revisions (7.0% vs 3.4%; OR = 2.14; 95% CI = 1.17–3.71; P = 0.008). Reasons for surgical strategy changes are listed in Supplementary Material, Table S3. Remeasurement after completed graft revisions showed improved HFUS/TTFM parameters in 88.9% of CKD/ESRD grafts and 82.4% of normal renal function grafts (SupplementaryMaterial, Table S4).

Secondary end points: transit-time flow measurement parameters

Post-protamine TTFM graft parameters for single-conduit to single-target grafts were compared between cohorts for 6 conduit/target combinations (Table 4). There were no significant group differences in the graft pulsatility index. Mean graft flow was significantly higher in the grafts of patients with CKD/ESRD for saphenous vein grafts to diagonal artery system targets (46 ml/min vs 32 ml/min; P = 0.047) and saphenous vein grafts to circumflex artery system targets (44 ml/min vs 34.5 ml/min; P = 0.042). Grafts excluded from analysis are detailed in Supplementary Material, Table S5.

In-hospital adverse events

In-hospital adverse event rates observed in patients with CKD/ESRD and with normal renal function can be found in Supplementary Material, Table S6.

DISCUSSION

Patients with CKD/ESRD have higher perioperative risk and worse outcomes after CABG than patients with normal renal function [2–5, 7]. Accordingly, many physicians are reluctant to recommend and perform CABG in this population, which leads to the underutilization of surgical revascularization in patients with CKD/ESRD despite society guideline recommendations [4, 6, 11]. To date, there is a paucity of literature describing differences in the operative course of CABG between patients with CKD/ESRD and those with normal renal function. We compared rates of surgical strategy changes and graft revisions between patients with CKD/ESRD and those with normal renal function undergoing CABG with an intraoperative assessment protocol using HFUS and TTFM.

Through a retrospective analysis of REQUEST data, we found that patients with CKD/ESRD present more intraoperative challenges during CABG, as manifested by a 39% greater rate of changes to preoperatively proposed surgical plans and/or graft revisions versus patients with normal renal function. This finding substantiates assumptions that increased lesion complexity and more diffuse CAD in patients with CKD/ESRD makes accurate preoperative procedural planning difficult, with more unexpected lesions or challenges to anastomosis construction encountered intraoperatively. In procedures performed by a highly experienced group of coronary surgeons, the majority of strategy changes and graft revisions overall in both cohorts were due to lesions identified only with HFUS and/or TTFM use. Patients with CKD/ESRD also had significantly greater strategy changes due to problems that were perceptible with visual/tactile inspection compared to patients with normal renal function. This group difference in visual/tactile changes was driven almost entirely by graft revisions (7.4% CKD/ESRD; 2.2% normal renal function). HFUS/TTFM imaging served a supporting and confirmatory role in graft verification in such instances; all patients with CKD/ESRD who had graft revisions based on visual/tactile inspection were assessed with TTFM beforehand (7/7) with 71% (5/7) also assessed with HFUS. A total of 85.7% (6/7) had reimaging performed after graft revision with TTFM and/or HFUS. Importantly, no operative deaths occurred among patients of either renal function cohort who underwent graft revision.

Surgical strategy changes and graft revisions due to lesions identified only with HFUS and/or TTFM use were 41% more frequently observed in patients with CKD/ESRD than in those with normal renal function. However, this finding did not meet statistical significance and was trend-level only, which is mostly reflective of the small comparative sample as suggested by the associated odds ratio and CI. Further studies specifically recruiting patients with CKD/ESRD to achieve greater power would be necessary to provide more definitive evidence that this effect exists. Regardless, whereas several lesions in patients with CKD/ESRD proved to be readily identifiable by visual/tactile means, it appears likely that the systematic use of HFUS/TTFM across all operative sites during CABG in patients with CKD/ESRD could potentially serve as an aid to identify many additional anatomical challenges that are not easily perceptible without such objective guidance. One particular area where scanning may be of particular benefit is at the ascending aorta, where 10.5% of patients with CKD/ESRD experienced strategy changes due to HFUS interrogation. Notably, no patients with CKD/ESRD in the REQUEST study experienced a stroke. Given that this population is more predisposed to systemic arterial calcification (associated with a heightened embolic risk on thoracic aortic cross-clamping), this finding may suggest epiaortic HFUS scanning as a strategy for confirming safe aortic handling and contributing to stroke prevention in patients with CKD/ESRD, which warrants further investigation [21, 22].

On post-protamine TTFM assessment of completed grafts, patients with CKD/ESRD achieved parameters for mean graft flow and pulsatility index that were comparable to those of patients with normal renal function across multiple conduit types and target territories. In 2 graft categories (saphenous vein graft to diagonal artery and saphenous vein graft to circumflex artery system), we observed statistically higher mean graft flow in grafts from patients with CKD/ESRD compared to patients with normal renal function. Certainly we are cautious to not overinterpret these findings, given the limited number of grafts of each type, especially within the CKD/ESRD cohort, as well as the high degree of anatomical variability of vein conduits and numerous other systemic factors affecting graft flow [23]. Nevertheless, our results suggest that despite the additional anatomical challenges in patients with CKD/ESRD, satisfactory TTFM measurements equivalent to those of patients with normal renal function can be achieved with appropriate graft construction and careful target vessel selection [24].

Limitations

There were some limitations to this study. First, the REQUEST study was not specifically designed to enroll patients with CKD/ESRD, and only 9.4% of trial participants had CKD/ESRD, an under-representation consistent with trends in many cardiovascular clinical trials [2, 5, 11]. Thus, we are underpowered in reporting some effects. Moreover, we did not have specific glomerular filtration rates available by which to stratify patients with CKD/ESRD by level of renal dysfunction. Additionally, because the follow-up period of the trial was limited to in-hospital events, it remains to be seen how differential rates of strategy changes impact (positively or even perhaps negatively) long-term clinical outcomes and graft patency [19]. Lastly, the REQUEST study was performed at high-volume centres with particularly experienced surgeons, as evidenced by the rates of off-pump CABG, bilateral internal thoracic artery use and complete arterial revascularization that far exceed those published in literature [25, 26]. Therefore, it is unclear how generalizable the experience of surgeons in the REQUEST study is to all cardiac surgery practices.

CONCLUSION

This study provides a unique insight into the operative course of patients with CKD/ESRD undergoing CABG. The findings suggest that patients with CKD/ESRD have added intraoperative challenges during CABG warranting increased rates of surgical strategy changes and graft revisions compared with patients with normal renal function. Additional studies in larger samples over longer follow-up periods are warranted to further correlate the incidence of such surgical strategy changes with respect to long-term graft patency and clinical outcomes.

SUPPLEMENTARY MATERIAL

Supplementary material is available at EJCTS online.

Presented at the 5th International Coronary Congress, New York, NY, USA, 6–8 December 2019.

ACKNOWLEDGEMENTS

We thank A. Pieter Kappetein and Stuart J. Head for leading the Erasmus University Medical Centre study site and the clinical coordinators at all participating sites.

Funding

This work was supported by the Medistim ASA, Oslo, Norway.

Conflict of interest: Gregory D. Trachiotis, Daniel Wendt, Teresa M. Kieser, John D. Puskas, Gabriele DiGiammarco received travelling support and/or speaking fees from Medistim. David P. Taggart received research funding and speaking and travelling honoraria from and acts as an adviser to Medistim. All other authors have declared no conflict of interest.

Author contributions

Ethan S. Rosenfeld: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing – original draft; Writing – review & editing. Gregory D. Trachiotis: Conceptualization; Investigation; Supervision; Validation; Writing – review & editing. Andrew D. Sparks: Data curation; Formal analysis; Methodology; Software; Writing – original draft; Writing – review & editing. Michael A. Napolitano: Data curation; Validation; Visualization; Writing – review & editing. K. Benjamin Lee: Conceptualization; Data curation; Writing – review & editing. Daniel Wendt: Conceptualization; Investigation; Validation; Writing – review & editing. Teresa M. Kieser: Conceptualization; Investigation; Validation; Writing – review & editing. John D. Puskas: Conceptualization; Investigation; Validation; Writing – review & editing. Gabriele DiGiammarco: Conceptualization; Investigation; Validation; Writing – review & editing. David P. Taggart: Conceptualization; Investigation; Methodology; Supervision;Validation; Writing – review & editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Mate Petricevic, Alexander Wahba and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.

REFERENCES

ABBREVIATIONS

 
• CABG

  Coronary artery bypass grafting

 
• CAD

  Coronary artery disease

 
• CI

  Confidence interval

 
• CKD

  Chronic kidney disease

 
• ESRD

  End-stage renal disease

 
• HFUS

  High-frequency ultrasound

 
• OR

  Odds ratio

 
• REQUEST

  REgistry for QUality assESsmenT with ultrasound imaging and TTFM in Cardiac Bypass Surgery

 
• TTFM

  Transit-time flow measurement