Abstract: Objectives. To investigate the feasibility and image quality of low-dose contrast computed tomography (CT) angiography with pulmonary artery (PA) protocol. Background. Aortic stenosis is the most common valvular heart disease and transcatheter aortic valve replacement (TAVR) has evolved as an alternative method for surgical valve replacement in intermediate-risk and high-risk surgical patients. CT is essential for measurement of aortic annulus prior to TAVR. Methods. Twenty patients underwent a low-dose contrast study with PA protocol and 20 patients underwent a traditional-dose study (traditional protocol). In PA protocol, the pigtail catheter was advanced in the main pulmonary artery under fluoroscopic guidance, with a second pigtail placed in the abdominal aorta. The pigtail catheter and sheath were secured in position and the patient was taken to the CT scan area for CT angiography of the chest (with injection from the PA catheter), abdomen, and pelvis (with injection from abdominal aortic catheter). Results. The amount of contrast used was significantly lower in the PA protocol vs the traditional protocol (40 mL vs 99.50 ± 6.87 mL; P<.001) at the cost of reduced average signal (265 ± 60 HU vs 371 ± 70 HU; P<.001), but without affecting measurements of the aortic annulus. Furthermore, no statistically significant difference in serum creatinine concentration was observed before and 48 hours after contrast administration in the PA group. Conclusion. Our data provide evidence that the new PA technique can be performed safely with much lower volume of CT contrast without affecting assessment of aortic annulus size.
J INVASIVE CARDIOL 2017;29(5):181-186.
Key words: aortic annulus, aortic valve stenosis, computed tomography
Aortic stenosis (AS) is the most common adult valvular heart disease in developed countries, with a prevalence approaching 12.4% in those who are 75 years of age and older.1 Although aortic valve replacement (AVR) is the treatment of choice for symptomatic AS, as the prognosis is poor for those managed conservatively,2,3 surgical morbidity and mortality can still be problematic in high-risk patients. Transcatheter aortic valve replacement (TAVR) is now indicated for patients with symptomatic AS who have high4 or intermediate estimated surgical risk,5,6 and studies are in progress evaluating lower-risk populations.7 In recent randomized trials, TAVR significantly improved survival and quality of life over standard medical therapy (including percutaneous balloon valvotomy) in patients with inoperable severe symptomatic AS.8-10 In patients considered high surgical risk, 30-day and 1-year mortality rates were similar between balloon-expandable TAVR and surgical AVR.11 Chronic kidney disease (CKD) is a common comorbidity, affecting 10%-25% of patients undergoing TAVR and associated with increased short-term postprocedure mortality.12
Although appropriate sizing of the TAVR valve for implantation initially relied upon measurements of the aortic annulus diameter based upon transthoracic and transesophageal echocardiographic images, the superiority of cardiac computed tomography (CT) imaging in the assessment of aortic root, aortic annulus, and left ventricular outflow tract (LVOT) anatomy and dimensions has been clearly demonstrated. The Society of Cardiovascular Computed Tomography (SCCT) currently recommends CT imaging be performed in all patients under consideration for TAVR unless there is a contraindication.13 A substantial volume of 80 mL to 120 mL of contrast is required for the scan, which can lead to contrast-induced nephropathy (CIN) in patients with preexisting CKD.4,12
In our institution, patients being evaluated for TAVR with CKD and serum creatinine of 1.6 mg/dL or greater are generally excluded from cardiac CT imaging because of the risk of CIN. In these patients, aorto-iliac CT angiography using selective and limited contrast injection (10 mL of contrast) through a pigtail catheter advanced into the infrarenal abdominal aorta has been employed for several years to determine suitability for transfemoral vascular access for TAVR.
We describe a novel technique in which a second pigtail catheter is placed into the pulmonary artery (PA) at the time of pigtail catheter placement in the abdominal aorta (for selective aorto-iliac CT angiography) in the cardiac catheterization laboratory and the patient is then transferred to the CT scanner, where low-dose contrast is injected for CT angiography of the chest, abdomen, and pelvis with and without contrast (PA protocol).
The present study compares CT image quality between traditional intravenous and low-volume contrast PA protocols.
Patient population. This study is a retrospective analysis of 40 patients who underwent CT angiography with either traditional intravenous or PA protocols using a Philips Brilliance iCT 256-slice CT scanner. Consecutive patients were included, all of whom had adequate study quality. Creatinine levels were obtained at baseline and 48 hours after the procedure. CIN was defined as either a 25% increase in serum creatinine from baseline or 0.5 mg/dL (44 µmol/L) increase in absolute value, at 48-72 hours of intravenous contrast.14,15 A total of 40 mL of contrast was administered to each PA protocol patient. The comparator group comprised patients with serum creatinine <1.6 g/dL who had undergone cardiac and aorto-iliac CT imaging using the standard intravenous contrast injection protocol (80-120 mL of contrast total).4 The study was approved by the institutional review board.
Pulmonary artery (PA) protocol. Patients in the PA protocol were brought to the cardiac catheterization laboratory and were sterilely prepped and draped per our standard cardiac catheterization protocol. Vascular access was obtained in the femoral artery and vein in the standard fashion. A 5 Fr diagnostic pigtail catheter was positioned in the abdominal aorta distal to the renal arteries under fluoroscopic guidance. A PA catheter was then advanced into the PA under fluoroscopic guidance. An exchange-length, 0.25˝ J-tipped wire was advanced through the PA catheter, with removal of the PA catheter over the wire. The exchange-length wire was then used to position a 5 Fr diagnostic pigtail catheter under fluoroscopic guidance in the main PA. The catheters and sheaths were secured in position and the patient was transported for immediate CT angiography of the chest, abdomen, and pelvis using the following sequence: (1) helically acquired non-contrast CT images of the chest, abdomen, and pelvis were obtained and reconstructed at 0.9 mm slice thickness at a 0.45 mm interval with multiplanar reformats; (2) a total of 60 cc of contrast mix (30 cc Omnipaque 350 [iohexol; GE Healthcare] diluted with 30 cc normal saline) at 10 cc/s was administered through the PA catheter; (3) the interventional cardiologist responsible for the procedure removed the pigtail catheters; and (4) the arterial and venous sheaths were removed and manual pressure was applied for hemostasis.
Helically acquired images were obtained with retrospective electrocardiographic gating (without dose modulation) from the mid neck through diaphragm and reconstructed with a slice thickness of 0.9 mm and 0.45 mm spacing. The tube voltage is 120kV, and automatic current modulation is used.
Next, small field of view dedicated cardiac CTA images are reconstructed at 35%, 40%, 45%, and 75% of the R-R interval with a slice thickness of 0.9 mm and 0.45 mm spacing.
All post processing is performed on the Vitrea workstation. Measurements of the annulus are made on the systolic phase reconstruction (35%, 40%, or 45%), which subjectively shows the least motion artifact. Occasionally, measurements from the 75% reconstructed images are necessary in the event of substantial motion artifact on the systolic phase images.
Abdomen and pelvis CTA. A separate contrast injection is performed through the infrarenal aortic pigtail catheter with a total volume of 40 cc contrast mix (10 cc Omnipaque 350 diluted in 30 cc normal saline) at 10 cc/s. Helically acquired images are obtained from the upper abdomen through the pelvis and reconstructed at 0.9 mm slice thickness and 0.45 mm spacing.
Image analysis. Three-dimensional volume-rendered and maximum intensity projection (MIP) reformats were reconstructed at 0.5 mm slice thickness on the Vitrea workstation. The data were loaded into a standard multiplanar cardiac reformat package with images reconstructed in the coronal, sagittal, and transverse (axial) orientations, and then analyzed using a multiplanar oblique tool.
Intravascular CT attenuation (Hounsfield units; HU) and image noise defined as standard deviation (SD) of CT attenuation were measured by using region of interest (ROI) analysis. ROI of approximately 250 mm2 was drawn above and below the aortic valve (to avoid measurement contamination by heavily calcified leaflets). Contrast density was calculated as average of above and below the valve ROI’s end (expressed in HU). Examples of patients who underwent traditional and PA protocol are presented in Figure 1. Signal and signal-to-noise ratio (SNR) is measured below the valve. Contrast-to-noise ratio (CNR) is calculated to assess signal intensity difference between two regions (below the valve and surrounding myocardium). Based on these measurements, SNR and CNR were calculated as:16
SNR = HUbelow the valve / noise
CNR = [HUbelow the valve – HUsurrounding muscle] / noise
Aortic annulus measurement. Aortic annulus, aortic root, and LVOT assessments and measurements for prospective clinical planning for TAVR were obtained from three-dimensional volume-rendered and MIP reformats performed utilizing 3mensio Structural Heart Analysis software, version 7.1 (Pie Medical Imaging). Images from three systolic phases (35%, 40%, and 45% of R-R intervals) were analyzed, and the largest aortic annulus area and perimeter measurements were used for choosing the appropriate TAVR valve size. Rarely, motion artifact in systolic phase required analysis of the aortic annulus and aortic root based upon the 75% R-R interval diastolic phase images.
Analysis of vascular access for the prospective planning of TAVR was performed using the 3mensio Vascular Analysis Package, version 7.1 (Pie Medical Imaging). Two-dimensional and three-dimensional reconstructions of the abdominal aorta, iliac, and femoral arteries were performed to assess suitability for transfemoral artery approach.
Statistical analysis. Continuous variables are expressed as mean ± standard deviation for normal distributions and median (interquartile range [IQR]) for non-normal distributions. Normality was tested using the Shapiro-Wilk test. For the evaluation of qualitative variables, we used the Chi-Squared test. Independent-sample t-test was used to compare age, body mass index (BMI), contrast volume, average signal, signal, SNR, and CNR between two groups. Mann-Whitney U-test was performed to test for significant differences between cardiac index in two groups. Wilcoxon Signed Rank test was used to compare serum creatinine concentration before and after administration of contrast agent. Pearson’s correlation coefficient (R) or Spearman’s rank correlation coefficient (Rs) test were used to test the association of variables with normal distribution or non-normal distribution, respectively. A P-value of <.05 was considered statistically significant. Statistical analysis was performed using the SPSS 22 software program (SPS, Inc).
The study consisted of 40 consecutive patients (20 in the PA group and 20 in the traditional group). The contrast volume was higher in the traditional group than in the PA group (P<.001). There were no differences in age, BMI, body surface area, or cardiac index between groups (Table 1). The average signal (P<.001), SNR (P<.01), and CNR (P=.02) were significantly higher in the traditional group vs the PA group (Table 2). The average signal in the traditional protocol was related to cardiac index (Rs = -0.773; P<.001), but not in the PA group (P=.82). Interestingly, there was a correlation between body surface area and average signal in the PA group (R= -0.528; P=.017), which was not observed in the traditional group (P=.41) (Figure 2). Aortic annulus measurement was feasible in all patients regardless of protocol. TAVR was performed successfully in all patients, with no more than mild perivalvular regurgitation. There were no complications related to the PA protocol. The median serum creatinine value in the patients undergoing PA protocol was 1.68 mg/dL (IQR, 1.58-2.24 mg/dL) before the administration of contrast and 1.81 (IQR, 1.49-2.37 mg/dL) 48 hours after the administration of contrast (difference was not statistically significant; P=.60). Only 1 of the 20 patients (5%) had an increase of at least 0.5 mg/dL in the serum creatinine concentration 48 hours after administration of the contrast agent.
This study demonstrates the feasibility of a reduced contrast cardiac CT protocol using selective contrast injection into the PA in the planning for TAVR. The evolution of TAVR has been rapid over the last 5 years, and it is now being performed at many centers with excellent short-term and long-term outcomes.4 CT plays a central role in patient selection and evaluation prior to TAVR. CT provides accurate dimensions of the thoracoabdominal aorta and its iliofemoral branches to optimize vascular access and approach, atherosclerotic burden, anatomy of the ascending aorta, aortic root, and valve annulus, which are of critical importance in valve type and size selection.13,17 However, the use of large volumes of intravenous contrast agent in CT can lead to CIN. CIN can be seen in >10% of patients after contrast-enhanced CT.18 In high-risk patients (including those with diabetes mellitus, CKD, history of congestive heart failure, and older age), CIN has been estimated at 20%-30%.19 In our reduced contrast PA protocol group, only 1 patient (5%) with multiple risk factors developed CIN after exposure to contrast agent. On the other hand, several studies have suggested that intravenous contrast volume is less nephrotoxic than intraarterial administration.20,21PA injection seems more similar to intraarterial and might be worse than a large dose given intravenously.
CIN can be associated with prolonged hospitalization, accelerated onset of end-stage renal disease, the requirement for dialysis, increased costs, and increased mortality.22 The presence of preexisting CKD is known to be a factor predisposing patients to acute kidney injury and is associated with worse outcome following TAVR.12 The most effective means of preventing CIN involves adequate hydration by intravenous saline,23 withholding nephrotoxic medications, and, most critically, the administration of the lowest possible volume of CT contrast.24 In comparison with the traditional technique, the main advantage of our PA protocol was the use of lower contrast volume, which may decrease the incidence of CIN. Some reduction in contrast density was noted, but accurate assessment of the aortic root, aortic annulus, and LVOT for planning TAVR was still achievable. In the low-volume contrast PA protocol patients, attenuation of contrast density did not affect measurements of the ascending aorta and aortic annulus. In addition, PA technique was not sensitive to cardiac index; as such, there was no need to adjust either contrast volume or timing of contrast injection to patient cardiac index. Spagnolo et al reported the results of a study to investigate the feasibility and image quality of 64-slice CT angiography using an ultra-low-dose contrast volume in 162 patients with BMI ≤29 kg/m2 scheduled for TAVR. CT angiography of the entire aorta with a multiphasic, low-iodine dose and BMI-adapted contrast protocol (BMI <22 kg/m2: 40 mL; BMI 22-29 kg/m2: 55 mL) was performed. Image quality of the aortic root and ilio-femoral vessels was evaluated in all patients. Vascular attenuation was >200 HU at any vessel level and measurements at the aortic annulus and iliac arteries were feasible with a substantial reduction of contrast volume.25 However, this study excluded patients with BMI >29 kg/m2, in contrast with our PA protocol, in which patients were not excluded on the basis of BMI.
The principal risk of our PA protocol is its invasive nature compared with peripheral intravenous contrast injection and need for separate injection from a second pigtail catheter placed in the abdominal aorta to visualize the aorto-iliac and femoral arteries. Although the risks from PA catheterization are well described, much of the risk is related to distal PA rupture from aggressive advancement of the catheter and balloon inflation-associated PA rupture. Our technique involves positioning of the catheter over an exchange-length guidewire in the main PA and avoidance of catheter and wire advancement into the distal peripheral PA bed. Meticulous catheter and guidewire manipulation under active fluoroscopic imaging can reduce the risk of serious vascular complications. To reduce the risk of vascular complications from the arterial puncture required for aorto-iliac and femoral artery imaging, we are currently evaluating a modification of our protocol in which peripheral arteries are visualized with a single PA injection: a test bolus of 4.5 cc of contrast (10 cc total, 45% contrast/55% saline) is injected from the PA catheter. The ROI is placed in the descending aorta at the level of the carina; the typical delay is 11-24 s, and the scan starts continuously from neck to pelvis to cover the carotid arteries.
Study limitations. The limitations of our study include its retrospective nature and relatively small sample size. Although only 1 patient (5%) in our PA protocol developed CIN, our study does not address whether the reduced contrast load in the PA protocol reduces CIN when compared with the standard intravenous contrast load. We did not adjust PA contrast dose depending on body surface area, although our data suggest that CT contrast image quality in patients with higher body surface area may benefit from higher contrast volume. In the current study, we used iohexol rather than iodixanol. However, iodixanol has been demonstrated to be less nephrotoxic.26
Our data provide evidence that the new PA technique can be performed safely, with substantially lower volume of CT contrast and with excellent procedural outcomes, without sacrificing image quality and ability to measure aortic annulus.
1. Osnabrugge RL, Mylotte D, Head SJ, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013;62:1002-1012.
2. Martinez-Selles M, Gomez Doblas JJ, Carro Hevia A, et al. Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention. J Intern Med. 2014;275:608-620.
3. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:e57-e185.
4. Holmes DR Jr, Mack MJ, Kaul S, et al. 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement: developed in collabration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Thorac Cardiovasc Surg. 2012;144:e29-e84.
5. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374:1609-1620.
6. Thourani VH, Kodali S, Makkar RR, et al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet. 2016;387:2218-2225. Epub 2016 Apr 3.
7. Thyregod HG, Steinbruchel DA, Ihlemann N, et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic valve stenosis: 1-year results from the all-comers NOTION randomized clinical trial. J Am Coll Cardiol. 2015;65:2184-2194.
8. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597-1607.
9. Kapadia SR, Leon MB, Makkar RR, et al. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015;385:2485-2491.
10. Kapadia SR, Tuzcu EM, Makkar RR, et al. Long-term outcomes of inoperable patients with aortic stenosis randomly assigned to transcatheter aortic valve replacement or standard therapy. Circulation. 2014;130:1483-1492.
11. Kodali SK, Williams MR, Smith CR, et al. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012;366:1686-1695.
12. Rahman MS, Sharma R, Brecker SJD. Transcatheter aortic valve implantation in patients with pre-existing chronic kidney disease. IJC Heart & Vasculature. 2015;8:9-18.
13. Achenbach S, Delgado V, Hausleiter J, Schoenhagen P, Min JK, Leipsic JA. SCCT expert consensus document on computed tomography imaging before transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve replacement (TAVR). J Cardiovasc Comput Tomogr. 2012;6:366-380.
14. Golshahi J, Nasri H, Gharipour M. Contrast-induced nephropathy; a literature review. J Nephropathology. 2014;3:51-56.
15. Feldkamp T, Kribben A. Contrast media induced nephropathy: definition, incidence, outcome, pathophysiology, risk factors and prevention. Minerva Med. 2008;99:177-196.
16. Geyer LL, De Cecco CN, Schoepf UJ, et al. Low-volume contrast medium protocol for comprehensive cardiac and aortoiliac CT assessment in the context of transcatheter aortic valve replacement. Academic Radiol. 2015;22:1138-1146.
17. Jurencak T, Turek J, Kietselaer BL, et al. MDCT evaluation of aortic root and aortic valve prior to TAVI. What is the optimal imaging time point in the cardiac cycle? Eur Radiol. 2015;25:1975-1983.
18. Mitchell AM, Jones AE, Tumlin JA, Kline JA. Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol. 2010;5:4-9. Epub 2009 Dec 3.
19. Tepel M, Aspelin P, Lameire N. Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation. 2006;113:1799-1806.
20. Solomon R. Contrast-induced acute kidney injury: is there a risk after intravenous contrast? Clin J Am Soc Nephrol. 2008;3:1242-1243.
21. Dong M, Jiao Z, Liu T, Guo F, Li G. Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials. J Nephrol. 2012;25:290-301.
22. Jorgensen AL. Contrast-induced nephropathy: pathophysiology and preventive strategies. Crit Care Nurse. 2013;33:37-46.
23. Weisbord SD, Palevsky PM. Prevention of contrast-induced nephropathy with volume expansion. Clin J Am Soc Nephrol. 2008;3:273-280.
24. Azzalini L, Spagnoli V, Ly HQ. Contrast-induced nephropathy: from pathophysiology to preventive strategies. Can J Cardiol. 2016;32:247-255.
25. Spagnolo P, Giglio M, Di Marco D, et al. Feasibility of ultra-low contrast 64-slice computed tomography angiography before transcatheter aortic valve implantation: a real-world experience. Eur Heart J Cardiovasc Imaging. 2016;17:24-33. Epub 2015 Jul 9.
26. Chalmers N, Jackson RW. Comparison of iodixanol and iohexol in renal impairment. Br J Radiol. 1999;72:701-703.
From 1The Christ Hospital Health Network, Cincinnati, Ohio; 2Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam; 3University of Cincinnati, College of Allied Health Sciences, Cincinnati, Ohio. The research was performed at The Christ Hospital Health Network, Cincinnati, Ohio.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted September 15, 2016, provisional acceptance given December 5, 2016, final version accepted February 3, 2017.
Address for correspondence: Wojciech Mazur, MD, The Christ Hospital Health Network, 2139 Auburn Avenue, Cincinnati, OH 45219. Email: firstname.lastname@example.org