Renal artery stenosis angioplasty and stenting: Difference between revisions
Jump to navigation
Jump to search
(/* 2013 ACC/AHA Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) (DO NOT EDIT){{cite journal| author=Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis R...) |
|||
| (12 intermediate revisions by 2 users not shown) | |||
| Line 1: | Line 1: | ||
__NOTOC__ | __NOTOC__ | ||
{{Renal artery stenosis}} | {{Renal artery stenosis}} | ||
{{CMG}}; | {{CMG}}; '''Associate Editor-In-Chief:''' {{Shivam Singla}} | ||
==Overview== | ==Overview== | ||
Randomized controlled trials such as ASTRAL (Angioplasty and Stenting for Renal Artery Lesions) | [[Randomized controlled trials]] such as [[ASTRAL]] (Angioplasty and Stenting for Renal Artery Lesions) and [[CORAL]] have not demonstrated a benefit of percutaneous [[revascularization]] over medical therapy among [[patients]] with [[unilateral]] [[renal artery stenosis]] (RAS). These [[trials]] have been criticized, however, because they did not enroll those [[patients]] who in observational data derived the greatest benefit, namely those [[patients]] who have a short duration of [[hypertension]], patients who are resistant to [[medical therapy]] for [[hypertension]], and [[patients]] who have recurrent flash [[pulmonary edema]]. For instance, in the [[ASTRAL]] trial, [[patients]] had [[hypertension]] for 5 years. Likewise, the mean number of [[antihypertensive]] agents was only 2.1 in the [[CORAL]] trial, and [[patients]] who were recently hospitalized with [[congestive heart failure]] were excluded from the [[CORAL trial]]. | ||
==Landmark Studies== | ==Landmark Studies== | ||
===ASTRAL Trial=== | ===ASTRAL Trial=== | ||
*The 2009 [[ASTRAL]] (Angioplasty and Stenting for Renal Artery Lesions) trial was an unblinded trial that randomized 806 patients with [[RAS]] for 5 years to either [[revascularization]] and medical therapy or medical therapy alone in a 1:1 ratio. | |||
*[[Angioplasty|Renal angioplasty]] was associated with significant risk and very little benefit in [[ASTRAL]].<ref name="pmid19907042">{{cite journal| author=ASTRAL Investigators. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG et al.| title=Revascularization versus medical therapy for renal-artery stenosis. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 20 | pages= 1953-62 | pmid=19907042 | doi=10.1056/NEJMoa0905368 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19907042 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20157130 Review in: Ann Intern Med. 2010 Feb 16;152(4):JC-26] </ref> | |||
*The rate of increase in [[creatinine]] was better among patients who underwent revascularization at -0.07x10<sup>-3</sup> L/mmol/year vs -0.13x10<sup>-3</sup> L/mmol/year among those treated with medical therapy. | |||
*Similarly, the mean serum [[creatinine]] was lower in the revascularization group; but the number of renal events was similar. Nonetheless, the reduction in [[blood pressure]] was better with medical therapy.<ref name="pmid19907042">{{cite journal| author=ASTRAL Investigators. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG et al.| title=Revascularization versus medical therapy for renal-artery stenosis. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 20 | pages= 1953-62 | pmid=19907042 | doi=10.1056/NEJMoa0905368 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19907042 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20157130 Review in: Ann Intern Med. 2010 Feb 16;152(4):JC-26] </ref> Furthermore, cardiovascular events and death were not significantly different; but the rates of serious complications during [[revascularization]] were high, involving 23 patients and including 2 deaths and 3 amputations.<ref name="pmid19907042">{{cite journal| author=ASTRAL Investigators. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG et al.| title=Revascularization versus medical therapy for renal-artery stenosis. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 20 | pages= 1953-62 | pmid=19907042 | doi=10.1056/NEJMoa0905368 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19907042 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20157130 Review in: Ann Intern Med. 2010 Feb 16;152(4):JC-26] </ref> | |||
== | ===CORAL Trial=== | ||
*In the 2013 [[CORAL]] trial, 947 patients with [[atherosclerotic]] [[renal-artery stenosis]] who had either [[chronic kidney disease]] or persistent [[systolic hypertension]] on > or = to 2 [[antihypertensive drugs]] were randomized to either [[renal-artery stenting]] + [[medical therapy]] or medical therapy alone. | |||
*After a median follow-up of 43 months, the primary endpoint (the composite of either death from cardiovascular or renal causes, [[myocardial infarction]], [[stroke]], hospitalization for [[congestive heart failure]], progressive [[renal insufficiency]], or the need for renal-replacement therapy) did not differ between the strategies: 35.1% and 35.8%; 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58, for stenting + medical therapy vs medical therapy alone); nor did any of the components of the primary endpoint (including mortality). | |||
*There was a modest benefit in [[systolic blood pressure]] reduction in the stented group (−2.3 mm Hg; 95% CI, −4.4 to −0.2; P=0.03). | |||
<br /> | |||
=== | == Indications for Renal Angioplasty or Stenting == | ||
Based upon the modest data observed in the above [[observational]] studies, the following are considered reasonable indications for [[percutaneous intervention]]:<ref name="pmid24074824">{{cite journal| author=Ritchie J, Green D, Chrysochou C, Chalmers N, Foley RN, Kalra PA| title=High-risk clinical presentations in atherosclerotic renovascular disease: prognosis and response to renal artery revascularization. | journal=Am J Kidney Dis | year= 2014 | volume= 63 | issue= 2 | pages= 186-97 | pmid=24074824 | doi=10.1053/j.ajkd.2013.07.020 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24074824 }} </ref><ref name="pmid19937777">{{cite journal| author=Kalra PA, Chrysochou C, Green D, Cheung CM, Khavandi K, Sixt S et al.| title=The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease. | journal=Catheter Cardiovasc Interv | year= 2010 | volume= 75 | issue= 1 | pages= 1-10 | pmid=19937777 | doi=10.1002/ccd.22290 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19937777 }} </ref> <ref name="pmid12710843">{{cite journal| author=Gray BH, Olin JW, Childs MB, Sullivan TM, Bacharach JM| title=Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure. | journal=Vasc Med | year= 2002 | volume= 7 | issue= 4 | pages= 275-9 | pmid=12710843 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12710843 }} </ref> | |||
*<u>Failure of [[medical therapy]] with [[persistent hypertension]] or a decline in [[renal]] function while on medical therapy</u> | |||
| | **[[Revascularization]] was recommended by ACC/AHA guidelines, with class B evidence, in [[hypertensive]] [[patients]] who have hemodynamically significant [[RAS]], [[malignant hypertension]], [[resistant hypertension]], and/or accelerated [[hypertension]], and among those with unexplained [[unilateral]] [[small kidneys]] or intolerance to anti-[[hypertensive]] [[medications]].<ref name="pmid23457117">{{cite journal| author=Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH et al.| title=Management of [[patients]] with [[peripheral artery disease]] (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2013 | volume= 127 | issue= 13 | pages= 1425-43 | pmid=23457117 | doi=10.1161/CIR.0b013e31828b82aa | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23457117 }} </ref> | ||
| | |||
*<u>Refractory [[heart failure]] and or recurrent [[flash pulmonary edema]]</u> | |||
**[[Revascularization]] was indicated at level B evidence in [[patients]] with [[thermodynamically]] significant [[RAS]] and [[recurrent]] [[congestive heart failure]] of undefined cause or in cases of sudden [[flash pulmonary edema]] with unexplained etiology, as well as for [[unstable angina]].<ref name="pmid23457117">{{cite journal| author=Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH et al.| title=Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2013 | volume= 127 | issue= 13 | pages= 1425-43 | pmid=23457117 | doi=10.1161/CIR.0b013e31828b82aa | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23457117 }} </ref> | |||
*<u>Brief duration of [[hypertension]] preceding the diagnosis of [[renal artery stenosis]]</u> | |||
<br /> | |||
{| | ==Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations) : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines<ref name="pmid23473760">{{cite journal| author=Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L et al.| title=Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2013 | volume= 61 | issue= 14 | pages= 1555-70 | pmid=23473760 | doi=10.1016/j.jacc.2013.01.004 | pmc=4492473 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23473760 }} </ref>== | ||
|- | {| class="wikitable" | ||
| | |+ | ||
!Indications for Revascularization of Asymptomatic Stenosis | |||
![[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]] | |||
<nowiki>"</nowiki>'''1.''' Percutaneous revascularization may be considered for the treatment of an asymptomatic bilateral or a solitary viable kidney with a hemodynamically significant RAS. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki> | |||
<nowiki>"</nowiki>'''2.''' The usefulness of percutaneous revascularization of an asymptomatic unilateral hemodynamically significant RAS in a viable kidney is not well established and is presently clinically unproven. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki> | |||
<br /> | |||
|- | |- | ||
| | |'''Hypertension''' | ||
|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|'''Class IIa''']] | |||
'''"1. Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and accelerated hypertension, [[resistant hypertension]], [[malignant hypertension]], [[hypertension]] with an unexplained unilateral small kidney, and hypertension with intolerance to medication. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>''' | |||
|- | |- | ||
| | |'''Preservation of Renal''' | ||
'''Function''' | |||
|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|'''Class IIa''']] | |||
'''"1. Percutaneous revascularization is reasonable for patients with RAS and progressive [[chronic kidney disease]] with bilateral RAS or a RAS to a solitary functioning kidney. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>''' | |||
[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|'''Class IIb''']] | |||
'''"1. Percutaneous revascularization may be considered for patients with RAS and [[chronic renal insufficiency]] with unilateral RAS. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>''' | |||
|- | |- | ||
| | |'''Impact of RAS on''' | ||
'''Congestive Heart''' | |||
'''Failure and Unstable''' | |||
'''Angina''' | |||
|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|'''Class I''']] | |||
'''"1. Percutaneous revascularization is indicated for patients with hemodynamically significant RAS and recurrent, unexplained [[congestive heart failure]] or sudden, unexplained [[pulmonary edema]] (see text). ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>''' | |||
[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|'''Class IIa''']] | |||
'''"1. Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and [[unstable angina]] (see text). ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>''' | |||
<br /> | |||
|- | |- | ||
| | |'''Endovascular''' | ||
'''Treatment for RAS''' | |||
|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|'''Class I''']] | |||
'''"1. Renal stent placement is indicated for ostial atherosclerotic RAS lesions that meet the clinical criteria for intervention. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>''' | |||
'''"2. [[Balloon angioplasty]] with bail-out stent placement if necessary is recommended for [[fibromuscular dysplasia]] lesions. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>''' | |||
|} | |} | ||
Latest revision as of 20:59, 12 December 2020
|
Renal artery stenosis Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Renal artery stenosis angioplasty and stenting On the Web |
|
American Roentgen Ray Society Images of Renal artery stenosis angioplasty and stenting |
|
Risk calculators and risk factors for Renal artery stenosis angioplasty and stenting |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Shivam Singla, M.D.[2]
Overview
Randomized controlled trials such as ASTRAL (Angioplasty and Stenting for Renal Artery Lesions) and CORAL have not demonstrated a benefit of percutaneous revascularization over medical therapy among patients with unilateral renal artery stenosis (RAS). These trials have been criticized, however, because they did not enroll those patients who in observational data derived the greatest benefit, namely those patients who have a short duration of hypertension, patients who are resistant to medical therapy for hypertension, and patients who have recurrent flash pulmonary edema. For instance, in the ASTRAL trial, patients had hypertension for 5 years. Likewise, the mean number of antihypertensive agents was only 2.1 in the CORAL trial, and patients who were recently hospitalized with congestive heart failure were excluded from the CORAL trial.
Landmark Studies
ASTRAL Trial
- The 2009 ASTRAL (Angioplasty and Stenting for Renal Artery Lesions) trial was an unblinded trial that randomized 806 patients with RAS for 5 years to either revascularization and medical therapy or medical therapy alone in a 1:1 ratio.
- Renal angioplasty was associated with significant risk and very little benefit in ASTRAL.[1]
- The rate of increase in creatinine was better among patients who underwent revascularization at -0.07x10-3 L/mmol/year vs -0.13x10-3 L/mmol/year among those treated with medical therapy.
- Similarly, the mean serum creatinine was lower in the revascularization group; but the number of renal events was similar. Nonetheless, the reduction in blood pressure was better with medical therapy.[1] Furthermore, cardiovascular events and death were not significantly different; but the rates of serious complications during revascularization were high, involving 23 patients and including 2 deaths and 3 amputations.[1]
CORAL Trial
- In the 2013 CORAL trial, 947 patients with atherosclerotic renal-artery stenosis who had either chronic kidney disease or persistent systolic hypertension on > or = to 2 antihypertensive drugs were randomized to either renal-artery stenting + medical therapy or medical therapy alone.
- After a median follow-up of 43 months, the primary endpoint (the composite of either death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy) did not differ between the strategies: 35.1% and 35.8%; 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58, for stenting + medical therapy vs medical therapy alone); nor did any of the components of the primary endpoint (including mortality).
- There was a modest benefit in systolic blood pressure reduction in the stented group (−2.3 mm Hg; 95% CI, −4.4 to −0.2; P=0.03).
Indications for Renal Angioplasty or Stenting
Based upon the modest data observed in the above observational studies, the following are considered reasonable indications for percutaneous intervention:[2][3] [4]
- Failure of medical therapy with persistent hypertension or a decline in renal function while on medical therapy
- Revascularization was recommended by ACC/AHA guidelines, with class B evidence, in hypertensive patients who have hemodynamically significant RAS, malignant hypertension, resistant hypertension, and/or accelerated hypertension, and among those with unexplained unilateral small kidneys or intolerance to anti-hypertensive medications.[5]
- Refractory heart failure and or recurrent flash pulmonary edema
- Revascularization was indicated at level B evidence in patients with thermodynamically significant RAS and recurrent congestive heart failure of undefined cause or in cases of sudden flash pulmonary edema with unexplained etiology, as well as for unstable angina.[5]
- Brief duration of hypertension preceding the diagnosis of renal artery stenosis
Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations) : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[6]
| Indications for Revascularization of Asymptomatic Stenosis | Class IIb
"1. Percutaneous revascularization may be considered for the treatment of an asymptomatic bilateral or a solitary viable kidney with a hemodynamically significant RAS. (Level of Evidence: C)" "2. The usefulness of percutaneous revascularization of an asymptomatic unilateral hemodynamically significant RAS in a viable kidney is not well established and is presently clinically unproven. (Level of Evidence: C)"
|
|---|---|
| Hypertension | Class IIa
"1. Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and accelerated hypertension, resistant hypertension, malignant hypertension, hypertension with an unexplained unilateral small kidney, and hypertension with intolerance to medication. (Level of Evidence: B)" |
| Preservation of Renal
Function |
Class IIa
"1. Percutaneous revascularization is reasonable for patients with RAS and progressive chronic kidney disease with bilateral RAS or a RAS to a solitary functioning kidney. (Level of Evidence: B)" "1. Percutaneous revascularization may be considered for patients with RAS and chronic renal insufficiency with unilateral RAS. (Level of Evidence: C)" |
| Impact of RAS on
Congestive Heart Failure and Unstable Angina |
Class I
"1. Percutaneous revascularization is indicated for patients with hemodynamically significant RAS and recurrent, unexplained congestive heart failure or sudden, unexplained pulmonary edema (see text). (Level of Evidence: B)" "1. Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and unstable angina (see text). (Level of Evidence: B)"
|
| Endovascular
Treatment for RAS |
Class I
"1. Renal stent placement is indicated for ostial atherosclerotic RAS lesions that meet the clinical criteria for intervention. (Level of Evidence: B)" "2. Balloon angioplasty with bail-out stent placement if necessary is recommended for fibromuscular dysplasia lesions. (Level of Evidence: B)" |
References
- ↑ 1.0 1.1 1.2 ASTRAL Investigators. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG; et al. (2009). "Revascularization versus medical therapy for renal-artery stenosis". N Engl J Med. 361 (20): 1953–62. doi:10.1056/NEJMoa0905368. PMID 19907042. Review in: Ann Intern Med. 2010 Feb 16;152(4):JC-26
- ↑ Ritchie J, Green D, Chrysochou C, Chalmers N, Foley RN, Kalra PA (2014). "High-risk clinical presentations in atherosclerotic renovascular disease: prognosis and response to renal artery revascularization". Am J Kidney Dis. 63 (2): 186–97. doi:10.1053/j.ajkd.2013.07.020. PMID 24074824.
- ↑ Kalra PA, Chrysochou C, Green D, Cheung CM, Khavandi K, Sixt S; et al. (2010). "The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease". Catheter Cardiovasc Interv. 75 (1): 1–10. doi:10.1002/ccd.22290. PMID 19937777.
- ↑ Gray BH, Olin JW, Childs MB, Sullivan TM, Bacharach JM (2002). "Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure". Vasc Med. 7 (4): 275–9. PMID 12710843.
- ↑ 5.0 5.1 Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH; et al. (2013). "Management of [[patients]] with [[peripheral artery disease]] (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. 127 (13): 1425–43. doi:10.1161/CIR.0b013e31828b82aa. PMID 23457117. URL–wikilink conflict (help)
- ↑ Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L; et al. (2013). "Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 61 (14): 1555–70. doi:10.1016/j.jacc.2013.01.004. PMC 4492473. PMID 23473760.