- Email: [email protected]
Clinical feasibility of myocardial computed tomographic perfusion imaging in patients with recent acute-onset chest pain
Letters to the Editor
195
Clinical feasibility of myocardial computed tomographic perfusion imaging in patients with recent acute-onset chest pain☆ Jesper James Linde a,b,⁎, Jens Dahlgaard Hove a, Jørgen Tobias Kühl b, Mathias Sørgaard b, Henning Kelbæk b, Walter Bjørn Nielsen a, Klaus Fuglsang Kofoed b,c a b c
Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Denmark Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Denmark Department of Radiology, The Diagnostic Centre, Rigshospitalet, University of Copenhagen, Denmark
a r t i c l e
i n f o
Article history: Received 9 March 2014 Accepted 31 March 2014 Available online 8 April 2014 Keywords: Myocardial CT perfusion Cardiac CT angiography Acute chest pain Adenosine
Myocardial CT perfusion (CTP) has been introduced as a potentially valuable add-on to CT angiography (CTA). [1,2]. However earlier studies were performed in highly selected high-risk populations already referred for invasive coronary angiography (ICA), a setting which may not be extrapolated to unselected low- and intermediate-risk patients. Whenever a new diagnostic test is considered for clinical implementation, it is important to evaluate the technique with regard to logistical robustness, patient comfort and safety in addition to observer variability of test results. We assessed the clinical feasibility of myocardial CT perfusion in a large unselected low-risk patient population in terms of CTP related safety, inter- and intra-observer reproducibility of CTP test results and the potential incremental clinical value of a combined CTA + CTP assessment, as compared to CTA alone. The study was performed as an observational part of the randomised controlled CATCH trial [3], which compared the clinical value of a CTA-guided approach to a conventional functional-based strategy in patients hospitalised on suspicion of acute coronary syndrome, but clinically stabile during index hospitalisation with sequential normal electrocardiograms and measurements of troponins. Exclusion criteria for undergoing adenosine stress-CTP examination were: Age ≤ 40 years for men and ≤ 50 years for women, known asthma, chronic obstructive pulmonary disease, Type 2 and 3 atrio-ventricular blockage, atrial fibrillation, reduced kidney function and known allergy to adenosine or contrast. The study was approved by the local ethical committee. Patients were scanned using 320-multi-detector computed tomography (Aquilion One, Toshiba Medical systems) and a reststress protocol with a 5 min pause between CTA/rest CTP image acquisition and start of adenosine infusion (0.14 mg/kg/min) infused over 4–5 min as previously described [4]. In patients with heart rate N60 bpm and systolic blood pressure N100 mm Hg, a cardio-selective beta-blocker was administered orally. CTA studies were interpreted in accordance with SCCT guidelines [5] blinded to CTP-results and ICA results. CTP at rest and during adenosine stress were interpreted blinded to the CTA and ICA findings by two independent readers in all patients for the assessment of inter-observer agreement. Intra☆ Responsibility: All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Department of Cardiology, The Heart Centre, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Tel.: +45 26797774; fax: + 45 38623755. E-mail address: [email protected] (J.J. Linde).
observer analysis was performed by one reader in 100 randomly selected patients. For myocardial perfusion image interpretation, a slice thickness of 3–5 mm, an average projection and a window/level of 300/150 HU was used for the detection of perfusion defects (PD). A PD was defined as a subendocardial or transmural decrease in attenuation density covering more than 1 segment. In patients who underwent ICA, the CTA and CTP results were subsequently unblinded and used in an integrated approach, in which a luminal CTA stenosis b50% was considered non-significant, a luminal stenosis ≥70% haemodynamically significant, whereas for luminal stenoses between 50 and 70%, the presence or absence of a corresponding reversible CTP defect, either confirmed or rejected haemodynamic significance. ICA was performed in accordance with routine clinical guidelines. Coronary diameter stenoses ≥70% and borderline stenoses (50–70%) with FFR measurements of b0.75 were considered significant. Of the 600 patients included in the CATCH trial, 266 patients were scheduled for adenosine stress CTP (Fig. 1). Due to contrast-related symptoms during rest image acquisition, 4 patients did not proceed to the stress scan, and in 11 patients (4%) the adenosine infusion was interrupted prematurely. Heart rate increased from 60 ± 9 bpm during rest CTA to 74 ± 12 bpm during adenosine stress (p b 0.0001). Mean radiation doses (interquartile range) was 3.2 (2.8–3.9) mSv at rest and 7.1 (5.6–8.7) mSv during adenosine stress (p b 0.0001) and 10.2 (8.4–12.4) mSv for the combined protocol. During stress-CTP cardiac motion artefacts were observed in 39% of the population, conebeam artefacts in 14%, respiratory artefacts in 4% and beam hardening in 1%. The corresponding artefact frequencies at rest-CTP were 18%, 5%, 2% and 1%. Based on stress CTP images 18 patients (7%) were deemed non-diagnostic by at least one of the CT
Fig. 1. Patient flow diagram. CTA — computed tomographic angiography, CTP — computed tomographic perfusion, LVEF — left ventricular ejection fraction.
196
Letters to the Editor
Fig. 2. Distribution of reversible and fixed myocardial CT perfusion (CTP) defects in patients with and without CTA stenoses ≥50%. CTA — computed tomographic angiography, CTP — computed tomographic perfusion.
reader. For the remaining 233 patients, an inter-observer agreement of 94% and a kappa coefficient of 0.75 for the identification of reversible and irreversible perfusion defects were recorded. Intraobserver agreement was 94% with a kappa coefficient of 0.75. The frequency of reversible and fixed CTP defects in patients with and without CTA luminal stenoses ≥ 50% is shown in Fig. 2. Abnormal CTP findings were virtually not observed in patients with CTA stenoses b50%, whereas more than half of the patients with ≥ 50% stenosis had perfusion abnormalities. Of the 251 patients enrolled in the study, 39 patients were referred for ICA and a significant coronary diameter stenosis was found in 23 patients (59%) in 35 vessels (30%). With an integrated approach of combining CTA + CTP findings, the positive predictive
value increased, compared to with CTA alone on a per patient and per vessel level (Fig. 3). We have demonstrated that myocardial CT perfusion is safe, since the procedure was only terminated prematurely due to safety concerns in 2% of patients. The overall radiation dose associated with this combined anatomic and functional assessment of CTA + CTP is higher compared to CTA alone, yet similar to radiation exposure associated with SPECT [6]. Cardiac motion was the most important type of artefact influencing image interpretation, however careful phase selection and inter-phase comparison allowed a conclusion to be made in all but 9 (4%) CTP cases. The intra- and interobserver reproducibility of CTP imaging was high, which is an important prerequisite for clinical implementation of CTP as an add-on to CTA. The fact that only half of the patients with CTA determined stenoses ≥ 50% had a corresponding perfusion defect supports the concern, that CTA alone has limited value to predict myocardial ischaemia, and corresponds well with earlier reports comparing CTA to other functional-based modalities [7–10]. Our results for the subgroup of patients undergoing ICA indicate that a combined CTA + CTP assessment could improve the PPV of CTA alone in concordance with previous reports [1,2]. Nevertheless, randomised trials are needed to confirm this finding. We conclude that myocardial CT perfusion imaging as a novel add-on to conventional CT coronary angiography is safe, reproducible and could offer important incremental diagnostic value in the future clinical management of patients with recent acute-onset chest pain. Drs. JJL, KFK and JTK have received lecturing fees from Toshiba Medical System. Dr JJL has received a grant from the Danish Heart Foundation [grant number 12-04-R90_A3921-22718]. In addition, this work was supported by the John and Birthe Meyer Foundation, the AP Møller and Chastine Mc-Kinney Møller Foundation and the Toyota Foundation. Research Radiographer Tina Bock-Pedersen, Chief Radiographer Kim Madsen and project nurses Kirsten Thrysøe and Christina Møller are thanked for their excellent technical assistance. References [1] Rochitte CE, George RT, Chen MY, et al. Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study. Eur Heart J 2014 May;35(17):1120–30. [2] Techasith T, Cury RC. Stress myocardial CT perfusion: an update and future perspective. JACC Cardiovasc Imaging 2011;4(8):905–16.
Fig. 3. Per patient (N = 39) and per vessel (N = 117) positive predictive values (PPV) values for CTA and combined CTA + CTP for the detection of significant coronary stenoses by invasive coronary angiography, including fractional flow reserve for characterisation of borderline stenoses. Error bars are 95% confidence interval. CTA — computed tomographic angiography, CTP — computed tomographic perfusion.
Letters to the Editor [3] Linde JJ, Kofoed KF, Sorgaard M, et al. Cardiac computed tomography guided treatment strategy in patients with recent acute-onset chest pain: results from the randomised, controlled trial: CArdiac cT in the treatment of acute CHest pain (CATCH). Int J Cardiol 2013 Oct 15;168(6):5257–62. [4] Kuhl JT, Linde JJ, Fuchs A, et al. Patterns of myocardial perfusion in humans evaluated with contrast-enhanced 320 multidetector computed tomography. Int J Cardiovasc Imaging 2012;28(7):1739–47. [5] Raff GL, Abidov A, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 2009;3(2):122–36. [6] Hesse B, Tagil K, Cuocolo A, et al. EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology. Eur J Nucl Med Mol Imaging 2005;32(7):855–97.
197
[7] Meijboom WB, Van Mieghem CA, van Pelt N, et al. Comprehensive assessment of coronary artery stenoses: computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina. J Am Coll Cardiol 2008;52(8):636–43. [8] Schuijf JD, Wijns W, Jukema JW, et al. Relationship between noninvasive coronary angiography with multi-slice computed tomography and myocardial perfusion imaging. J Am Coll Cardiol 2006;48(12):2508–14. [9] Di Carli MF, Dorbala S, Curillova Z, et al. Relationship between CT coronary angiography and stress perfusion imaging in patients with suspected ischemic heart disease assessed by integrated PET-CT imaging. J Nucl Cardiol 2007;14(6):799–809. [10] Kristensen TS, Engstrom T, Kelbaek H, von der Recke P, Nielsen MB, Kofoed KF. Correlation between coronary computed tomographic angiography and fractional flow reserve. Int J Cardiol 2010;144(2):200–5.
http://dx.doi.org/10.1016/j.ijcard.2014.03.209 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Bicuspid aortic valve disease and lipoprotein(a)—A concept worth exploring? James Ker ⁎ Department of Internal Medicine, University of Pretoria, Pretoria, South Africa
a r t i c l e
i n f o
Article history: Received 22 February 2014 Accepted 31 March 2014 Available online 12 April 2014 Keywords: Bicuspid Aortic Valve Calcification Lipoprotein(a)
Bicuspid aortic valve (BAV) disease is the most common form of congenital heart disease with a prevalence of 1–2% in the population [1,2]. For the clinician BAV is the most important congenital cardiac lesion, because this results in more morbidity than all other congenital cardiac lesions combined [1,3,4]. This can be a sporadic or familial affliction with a male to female ratio of 3–4:1 [1,2]. A bicuspid aortic valve is the end result of a complex developmental abnormality and is not simply the result of the fusion of two normal cusps [1]. This is a diverse and complex condition with a significant morphological variability [1,5,6]. The following phenotypes of BAV can be seen 7. The two groups of BAV are: i) those with a raphe and ii) those without a raphe. The group with a raphe has the following possibilities and thus phenotypes: i) fusion of the right- and left-coronary cusps, ii) fusion of the right coronary and non-coronary cusps, and iii) fusion of the left coronary and non-coronary cusps. The group without a raphe is classified according to the orientation of the free edge of the cusps. This can be either anterior–posterior (BAV-AP) or lateral (BAV-LA) [7]. The major clinical significance of this common condition is the fact that only 20% of such patients will maintain a functioning valve throughout their lifetime [1,8]. The complication includes aortic dissection, infective endocarditis, aortic regurgitation and aortic stenosis [1,9]. The creasing of the BAV and resultant turbulent flow is currently thought to contribute to the calcification of such valves [2,10]. Recently a genomewide association study by Thanassoulis et al. [11] identified a SNP in the LPA locus that is significantly associated ⁎ Tel.: + 27 128092810. E-mail address: [email protected].
with aortic valve calcification in cases of normal aortic valves. Specifically, that study implicates genetic variants at the LPA locus with elevated plasma lipoprotein(a) levels as a cause for aortic valve calcification in the general population with normal aortic valves [11]. This leads to the clinical question of whether lipoprotein(a) may be an important role player in calcification of the bicuspid aortic valve? The purpose of this observational study was thus to correlate the plasma lipoprotein(a) level with the presence or absence of calcification of bicuspid aortic valves. This is an observational study looking at 10 cases of BAV disease— all discovered incidentally. These 10 cases were chosen as no other diseases were present, no medication was used by any of the patients and they were all asymptomatic. The absence or presence of calcification of the bicuspid aortic valve was documented in each case and the plasma lipoprotein(a) level was measured in each case. The echocardiographic images of the 10 cases of BAV disease are displayed as Figs. 1–10. Of these 10 cases, 4 clearly demonstrates calcification (Figs 2, 4, 5 and 10). All of the cases without calcification has normal plasma lipoprotein(a) levels. 3 of the 4 cases with calcification has elevated plasma lipoprotein(a) levels. In this case series a male predominance is seen which correlates with the current literature [1,2]. The youngest patient with calcification is 38 years old and the oldest patient without calcification is 55 years old.
Sex
Age
Calcification
Lipoprotein(a)
1. M 2. M 3. M 4. M 5. F 6. M 7. M 8. M 9. M 10. M
27 years
No
Normal
38 years
Yes
Elevated
50 years
No
Normal
47 years
Yes
Elevated
54 years
Yes
Elevated
41 years
No
Normal
24 years
No
Normal
55 years
No
Normal
28 years
No
Normal
45 years
Yes
Normal
195
Clinical feasibility of myocardial computed tomographic perfusion imaging in patients with recent acute-onset chest pain☆ Jesper James Linde a,b,⁎, Jens Dahlgaard Hove a, Jørgen Tobias Kühl b, Mathias Sørgaard b, Henning Kelbæk b, Walter Bjørn Nielsen a, Klaus Fuglsang Kofoed b,c a b c
Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Denmark Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Denmark Department of Radiology, The Diagnostic Centre, Rigshospitalet, University of Copenhagen, Denmark
a r t i c l e
i n f o
Article history: Received 9 March 2014 Accepted 31 March 2014 Available online 8 April 2014 Keywords: Myocardial CT perfusion Cardiac CT angiography Acute chest pain Adenosine
Myocardial CT perfusion (CTP) has been introduced as a potentially valuable add-on to CT angiography (CTA). [1,2]. However earlier studies were performed in highly selected high-risk populations already referred for invasive coronary angiography (ICA), a setting which may not be extrapolated to unselected low- and intermediate-risk patients. Whenever a new diagnostic test is considered for clinical implementation, it is important to evaluate the technique with regard to logistical robustness, patient comfort and safety in addition to observer variability of test results. We assessed the clinical feasibility of myocardial CT perfusion in a large unselected low-risk patient population in terms of CTP related safety, inter- and intra-observer reproducibility of CTP test results and the potential incremental clinical value of a combined CTA + CTP assessment, as compared to CTA alone. The study was performed as an observational part of the randomised controlled CATCH trial [3], which compared the clinical value of a CTA-guided approach to a conventional functional-based strategy in patients hospitalised on suspicion of acute coronary syndrome, but clinically stabile during index hospitalisation with sequential normal electrocardiograms and measurements of troponins. Exclusion criteria for undergoing adenosine stress-CTP examination were: Age ≤ 40 years for men and ≤ 50 years for women, known asthma, chronic obstructive pulmonary disease, Type 2 and 3 atrio-ventricular blockage, atrial fibrillation, reduced kidney function and known allergy to adenosine or contrast. The study was approved by the local ethical committee. Patients were scanned using 320-multi-detector computed tomography (Aquilion One, Toshiba Medical systems) and a reststress protocol with a 5 min pause between CTA/rest CTP image acquisition and start of adenosine infusion (0.14 mg/kg/min) infused over 4–5 min as previously described [4]. In patients with heart rate N60 bpm and systolic blood pressure N100 mm Hg, a cardio-selective beta-blocker was administered orally. CTA studies were interpreted in accordance with SCCT guidelines [5] blinded to CTP-results and ICA results. CTP at rest and during adenosine stress were interpreted blinded to the CTA and ICA findings by two independent readers in all patients for the assessment of inter-observer agreement. Intra☆ Responsibility: All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Department of Cardiology, The Heart Centre, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Tel.: +45 26797774; fax: + 45 38623755. E-mail address: [email protected] (J.J. Linde).
observer analysis was performed by one reader in 100 randomly selected patients. For myocardial perfusion image interpretation, a slice thickness of 3–5 mm, an average projection and a window/level of 300/150 HU was used for the detection of perfusion defects (PD). A PD was defined as a subendocardial or transmural decrease in attenuation density covering more than 1 segment. In patients who underwent ICA, the CTA and CTP results were subsequently unblinded and used in an integrated approach, in which a luminal CTA stenosis b50% was considered non-significant, a luminal stenosis ≥70% haemodynamically significant, whereas for luminal stenoses between 50 and 70%, the presence or absence of a corresponding reversible CTP defect, either confirmed or rejected haemodynamic significance. ICA was performed in accordance with routine clinical guidelines. Coronary diameter stenoses ≥70% and borderline stenoses (50–70%) with FFR measurements of b0.75 were considered significant. Of the 600 patients included in the CATCH trial, 266 patients were scheduled for adenosine stress CTP (Fig. 1). Due to contrast-related symptoms during rest image acquisition, 4 patients did not proceed to the stress scan, and in 11 patients (4%) the adenosine infusion was interrupted prematurely. Heart rate increased from 60 ± 9 bpm during rest CTA to 74 ± 12 bpm during adenosine stress (p b 0.0001). Mean radiation doses (interquartile range) was 3.2 (2.8–3.9) mSv at rest and 7.1 (5.6–8.7) mSv during adenosine stress (p b 0.0001) and 10.2 (8.4–12.4) mSv for the combined protocol. During stress-CTP cardiac motion artefacts were observed in 39% of the population, conebeam artefacts in 14%, respiratory artefacts in 4% and beam hardening in 1%. The corresponding artefact frequencies at rest-CTP were 18%, 5%, 2% and 1%. Based on stress CTP images 18 patients (7%) were deemed non-diagnostic by at least one of the CT
Fig. 1. Patient flow diagram. CTA — computed tomographic angiography, CTP — computed tomographic perfusion, LVEF — left ventricular ejection fraction.
196
Letters to the Editor
Fig. 2. Distribution of reversible and fixed myocardial CT perfusion (CTP) defects in patients with and without CTA stenoses ≥50%. CTA — computed tomographic angiography, CTP — computed tomographic perfusion.
reader. For the remaining 233 patients, an inter-observer agreement of 94% and a kappa coefficient of 0.75 for the identification of reversible and irreversible perfusion defects were recorded. Intraobserver agreement was 94% with a kappa coefficient of 0.75. The frequency of reversible and fixed CTP defects in patients with and without CTA luminal stenoses ≥ 50% is shown in Fig. 2. Abnormal CTP findings were virtually not observed in patients with CTA stenoses b50%, whereas more than half of the patients with ≥ 50% stenosis had perfusion abnormalities. Of the 251 patients enrolled in the study, 39 patients were referred for ICA and a significant coronary diameter stenosis was found in 23 patients (59%) in 35 vessels (30%). With an integrated approach of combining CTA + CTP findings, the positive predictive
value increased, compared to with CTA alone on a per patient and per vessel level (Fig. 3). We have demonstrated that myocardial CT perfusion is safe, since the procedure was only terminated prematurely due to safety concerns in 2% of patients. The overall radiation dose associated with this combined anatomic and functional assessment of CTA + CTP is higher compared to CTA alone, yet similar to radiation exposure associated with SPECT [6]. Cardiac motion was the most important type of artefact influencing image interpretation, however careful phase selection and inter-phase comparison allowed a conclusion to be made in all but 9 (4%) CTP cases. The intra- and interobserver reproducibility of CTP imaging was high, which is an important prerequisite for clinical implementation of CTP as an add-on to CTA. The fact that only half of the patients with CTA determined stenoses ≥ 50% had a corresponding perfusion defect supports the concern, that CTA alone has limited value to predict myocardial ischaemia, and corresponds well with earlier reports comparing CTA to other functional-based modalities [7–10]. Our results for the subgroup of patients undergoing ICA indicate that a combined CTA + CTP assessment could improve the PPV of CTA alone in concordance with previous reports [1,2]. Nevertheless, randomised trials are needed to confirm this finding. We conclude that myocardial CT perfusion imaging as a novel add-on to conventional CT coronary angiography is safe, reproducible and could offer important incremental diagnostic value in the future clinical management of patients with recent acute-onset chest pain. Drs. JJL, KFK and JTK have received lecturing fees from Toshiba Medical System. Dr JJL has received a grant from the Danish Heart Foundation [grant number 12-04-R90_A3921-22718]. In addition, this work was supported by the John and Birthe Meyer Foundation, the AP Møller and Chastine Mc-Kinney Møller Foundation and the Toyota Foundation. Research Radiographer Tina Bock-Pedersen, Chief Radiographer Kim Madsen and project nurses Kirsten Thrysøe and Christina Møller are thanked for their excellent technical assistance. References [1] Rochitte CE, George RT, Chen MY, et al. Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study. Eur Heart J 2014 May;35(17):1120–30. [2] Techasith T, Cury RC. Stress myocardial CT perfusion: an update and future perspective. JACC Cardiovasc Imaging 2011;4(8):905–16.
Fig. 3. Per patient (N = 39) and per vessel (N = 117) positive predictive values (PPV) values for CTA and combined CTA + CTP for the detection of significant coronary stenoses by invasive coronary angiography, including fractional flow reserve for characterisation of borderline stenoses. Error bars are 95% confidence interval. CTA — computed tomographic angiography, CTP — computed tomographic perfusion.
Letters to the Editor [3] Linde JJ, Kofoed KF, Sorgaard M, et al. Cardiac computed tomography guided treatment strategy in patients with recent acute-onset chest pain: results from the randomised, controlled trial: CArdiac cT in the treatment of acute CHest pain (CATCH). Int J Cardiol 2013 Oct 15;168(6):5257–62. [4] Kuhl JT, Linde JJ, Fuchs A, et al. Patterns of myocardial perfusion in humans evaluated with contrast-enhanced 320 multidetector computed tomography. Int J Cardiovasc Imaging 2012;28(7):1739–47. [5] Raff GL, Abidov A, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 2009;3(2):122–36. [6] Hesse B, Tagil K, Cuocolo A, et al. EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology. Eur J Nucl Med Mol Imaging 2005;32(7):855–97.
197
[7] Meijboom WB, Van Mieghem CA, van Pelt N, et al. Comprehensive assessment of coronary artery stenoses: computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina. J Am Coll Cardiol 2008;52(8):636–43. [8] Schuijf JD, Wijns W, Jukema JW, et al. Relationship between noninvasive coronary angiography with multi-slice computed tomography and myocardial perfusion imaging. J Am Coll Cardiol 2006;48(12):2508–14. [9] Di Carli MF, Dorbala S, Curillova Z, et al. Relationship between CT coronary angiography and stress perfusion imaging in patients with suspected ischemic heart disease assessed by integrated PET-CT imaging. J Nucl Cardiol 2007;14(6):799–809. [10] Kristensen TS, Engstrom T, Kelbaek H, von der Recke P, Nielsen MB, Kofoed KF. Correlation between coronary computed tomographic angiography and fractional flow reserve. Int J Cardiol 2010;144(2):200–5.
http://dx.doi.org/10.1016/j.ijcard.2014.03.209 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Bicuspid aortic valve disease and lipoprotein(a)—A concept worth exploring? James Ker ⁎ Department of Internal Medicine, University of Pretoria, Pretoria, South Africa
a r t i c l e
i n f o
Article history: Received 22 February 2014 Accepted 31 March 2014 Available online 12 April 2014 Keywords: Bicuspid Aortic Valve Calcification Lipoprotein(a)
Bicuspid aortic valve (BAV) disease is the most common form of congenital heart disease with a prevalence of 1–2% in the population [1,2]. For the clinician BAV is the most important congenital cardiac lesion, because this results in more morbidity than all other congenital cardiac lesions combined [1,3,4]. This can be a sporadic or familial affliction with a male to female ratio of 3–4:1 [1,2]. A bicuspid aortic valve is the end result of a complex developmental abnormality and is not simply the result of the fusion of two normal cusps [1]. This is a diverse and complex condition with a significant morphological variability [1,5,6]. The following phenotypes of BAV can be seen 7. The two groups of BAV are: i) those with a raphe and ii) those without a raphe. The group with a raphe has the following possibilities and thus phenotypes: i) fusion of the right- and left-coronary cusps, ii) fusion of the right coronary and non-coronary cusps, and iii) fusion of the left coronary and non-coronary cusps. The group without a raphe is classified according to the orientation of the free edge of the cusps. This can be either anterior–posterior (BAV-AP) or lateral (BAV-LA) [7]. The major clinical significance of this common condition is the fact that only 20% of such patients will maintain a functioning valve throughout their lifetime [1,8]. The complication includes aortic dissection, infective endocarditis, aortic regurgitation and aortic stenosis [1,9]. The creasing of the BAV and resultant turbulent flow is currently thought to contribute to the calcification of such valves [2,10]. Recently a genomewide association study by Thanassoulis et al. [11] identified a SNP in the LPA locus that is significantly associated ⁎ Tel.: + 27 128092810. E-mail address: [email protected].
with aortic valve calcification in cases of normal aortic valves. Specifically, that study implicates genetic variants at the LPA locus with elevated plasma lipoprotein(a) levels as a cause for aortic valve calcification in the general population with normal aortic valves [11]. This leads to the clinical question of whether lipoprotein(a) may be an important role player in calcification of the bicuspid aortic valve? The purpose of this observational study was thus to correlate the plasma lipoprotein(a) level with the presence or absence of calcification of bicuspid aortic valves. This is an observational study looking at 10 cases of BAV disease— all discovered incidentally. These 10 cases were chosen as no other diseases were present, no medication was used by any of the patients and they were all asymptomatic. The absence or presence of calcification of the bicuspid aortic valve was documented in each case and the plasma lipoprotein(a) level was measured in each case. The echocardiographic images of the 10 cases of BAV disease are displayed as Figs. 1–10. Of these 10 cases, 4 clearly demonstrates calcification (Figs 2, 4, 5 and 10). All of the cases without calcification has normal plasma lipoprotein(a) levels. 3 of the 4 cases with calcification has elevated plasma lipoprotein(a) levels. In this case series a male predominance is seen which correlates with the current literature [1,2]. The youngest patient with calcification is 38 years old and the oldest patient without calcification is 55 years old.
Sex
Age
Calcification
Lipoprotein(a)
1. M 2. M 3. M 4. M 5. F 6. M 7. M 8. M 9. M 10. M
27 years
No
Normal
38 years
Yes
Elevated
50 years
No
Normal
47 years
Yes
Elevated
54 years
Yes
Elevated
41 years
No
Normal
24 years
No
Normal
55 years
No
Normal
28 years
No
Normal
45 years
Yes
Normal