Peripheral arterial disease other imaging findings: Difference between revisions

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{{Peripheral arterial disease}}
{{Peripheral arterial disease}}


'''Editors-in-Chief: [[C. Michael Gibson]], M.D., Beth Israel Deaconess Medical Center, Boston, MA; [[User:Bobby Schwartz|Robert G. Schwartz, M.D.]] [mailto:RGSHEAL@aol.com], [http://www.piedmontpmr.com Piedmont Physical Medicine and Rehabilitation, P.A.]; '''Associate Editor-In-Chief:''' {{CZ}}
{{CMG}}; {{AE}} {{CZ}}; {{VVS}}; [[User:Rim Halaby|Rim Halaby]]


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==Overview==
When symptoms suggestive of [[peripheral artery disease]] are present, clinical evaluation along with non invasive testing are enough to establish the diagnosis. Invasive diagnostic studies are anatomic studies that are not used for diagnosis but rather for preoperative evaluation of the anatomy of the [[vessels]]. The invasive diagnostic studies, which are basically anatomic studies that rely on imaging, include conventional [[angiography]], CT angiography, [[MRA]] and duplex [[ultrasound]].


==Overview==
== Other Imaging Findings ==
===Conventional Angiography===
* Conventional [[angiography]] is considered as the standard in the invasive evaluation of [[peripheral artery disease]].
* It is very [[accurate]] in providing detailed evaluation of the structures of the [[vessels]].
* The down sides of conventional [[angiography]] are:
** Risk of damage at puncture site.
** Risk of distal [[embolization]].
** Limitation of use because of the administration of contrast material:
***In people will renal insufficiency
***In patients with [[allergy]] to contrast.<ref name="pmid16545667">{{cite journal| author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL et al.| title=ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 6 | pages= 1239-312 | pmid=16545667 | doi=10.1016/j.jacc.2005.10.009 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16545667  }} </ref><ref>Wennberg PW, Rooke TW. Chapter 109. Diagnosis and Management of Diseases of the Peripheral Arteries and Veins. In: Fuster V, Walsh RA, Harrington RA, eds. Hurst's The Heart. 13th ed. New York: McGraw-Hill; 2011.</ref>


== Other Imaging findings ==
==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>==
*Continuous wave doppler ultrasound
==ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>==


=== Recommendations for Continuous-Wave Doppler Ultrasound ===
=== Continuous-Wave Doppler Ultrasound (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>===


{|class="wikitable"
{|class="wikitable"
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|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Continuous-wave Doppler ultrasound blood flow measurements are useful to provide an accurate assessment of lower extremity PAD location and severity, to follow lower extremity PAD progression, and to provide quantitative follow-up after revascularization procedures. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Continuous-wave Doppler ultrasound blood flow measurements are useful to provide an accurate assessment of lower extremity PAD location and severity, to follow lower extremity PAD progression, and to provide quantitative follow-up after [[revascularization]] procedures. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
|}


=== Recommendations for Contrast Angiography ===
===Contrast Angiography (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>===
 
{|class="wikitable"
{|class="wikitable"
|-
|-
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|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Contrast angiography provides detailed information
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Contrast angiography provides detailed information about arterial anatomy and is recommended for evaluation of patients with lower extremity PAD when [[revascularization]] is contemplated. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
about arterial anatomy and is recommended for evaluation
 
of patients with lower extremity PAD when
|-
revascularization is contemplated. (Level of Evidence:
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' A history of contrast reaction should be documented before the performance of contrast angiography and appropriate pretreatment administered before contrast is given. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
B)
 
2. A history of contrast reaction should be documented
|-
before the performance of contrast angiography and
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' Decisions regarding the potential utility of invasive therapeutic interventions (percutaneous or surgical) in patients with lower extremity PAD should be made with a complete anatomic assessment of the affected arterial territory, including imaging of the occlusive lesion, as well as arterial inflow and outflow with [[angiography]] or a combination of angiography and noninvasive vascular techniques. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
appropriate pretreatment administered before contrast
 
is given. (Level of Evidence: B)
|-
3. Decisions regarding the potential utility of invasive
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' Digital subtraction angiography is recommended for contrast angiographic studies because this technique allows for enhanced imaging capabilities compared with conventional unsubtracted contrast angiography. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
therapeutic interventions (percutaneous or surgical)
 
in patients with lower extremity PAD should be made
|-
with a complete anatomic assessment of the affected
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' Before performance of contrast angiography, a full history and complete vascular examination should be performed to optimize decisions regarding the access site, as well as to minimize contrast dose and [[catheter]] manipulation. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
arterial territory, including imaging of the occlusive
 
lesion, as well as arterial inflow and outflow with
|-
angiography or a combination of angiography and
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''6.''' Selective or superselective catheter placement during lower extremity angiography is indicated because this can enhance imaging, reduce contrast dose, and improve sensitivity and specificity of the procedure. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
noninvasive vascular techniques. (Level of Evidence:
 
B)
|-
4. Digital subtraction angiography is recommended for
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''7.''' The diagnostic lower extremity [[arteriogram]] should image the iliac, femoral, and tibial bifurcations in profile without vessel overlap. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
contrast angiographic studies because this technique
 
allows for enhanced imaging capabilities compared
|-
with conventional unsubtracted contrast angiography.
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''8.''' When conducting a diagnostic lower extremity arteriogram in which the significance of an obstructive lesion is ambiguous, transstenotic pressure gradients and supplementary angulated views should beobtained. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
(Level of Evidence: A)
 
5. Before performance of contrast angiography, a full
|-
history and complete vascular examination should be
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''9.''' Patients with baseline [[renal insufficiency]] should receive hydration before undergoing contrast angiography. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
performed to optimize decisions regarding the access
 
site, as well as to minimize contrast dose and catheter
|-
manipulation. (Level of Evidence: C)
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''10.''' Follow-up clinical evaluation, including a physical examination and measurement of renal function, is recommended within 2 weeks after contrast angiography to detect the presence of delayed adverse effects, such as [[atheroembolism]], deterioration in renal function, or access site injury (e.g., [[pseudoaneurysm]] or [[arteriovenous fistula]]). ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
6. Selective or superselective catheter placement during
|}
lower extremity angiography is indicated because this
 
can enhance imaging, reduce contrast dose, and
{|class="wikitable"
improve sensitivity and specificity of the procedure.
|-
(Level of Evidence: C)
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIa]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Noninvasive imaging modalities, including [[MRA]], [[CTA]], and color flow duplex imaging, may be used in advance of invasive imaging to develop an individualized diagnostic strategic plan, including assistance in selection of access sites, identification of significant lesions, and determination of the need for invasive evaluation. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Treatment with [[n-acetylcysteine]] in advance of contrast angiography is suggested for patients with baseline [[renal insufficiency]] ([[creatinine]] greater than 2.0 mg per dL). ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
|}


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Latest revision as of 20:23, 6 October 2020

Peripheral arterial disease Microchapters

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AHA/ACC Guidelines on Management of Lower Extremity PAD

Guidelines for Clinical Assessment of Lower Extremity PAD

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Guidelines for Screening for Atherosclerotic Disease in Other Vascular Beds in patients with Lower Extremity PAD

Guidelines for Medical Therapy for Lower Extremity PAD

Guidelines for Structured Exercise Therapy for Lower Extremity PAD

Guidelines for Minimizing Tissue Loss in Lower Extremity PAD

Guidelines for Revascularization of Claudication in Lower Extremity PAD

Guidelines for Management of CLI in Lower Extremity PAD

Guidelines for Management of Acute Limb Ischemial in Lower Extremity PAD

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Vishnu Vardhan Serla M.B.B.S. [3]; Rim Halaby

Overview

When symptoms suggestive of peripheral artery disease are present, clinical evaluation along with non invasive testing are enough to establish the diagnosis. Invasive diagnostic studies are anatomic studies that are not used for diagnosis but rather for preoperative evaluation of the anatomy of the vessels. The invasive diagnostic studies, which are basically anatomic studies that rely on imaging, include conventional angiography, CT angiography, MRA and duplex ultrasound.

Other Imaging Findings

Conventional Angiography

  • Conventional angiography is considered as the standard in the invasive evaluation of peripheral artery disease.
  • It is very accurate in providing detailed evaluation of the structures of the vessels.
  • The down sides of conventional angiography are:
    • Risk of damage at puncture site.
    • Risk of distal embolization.
    • Limitation of use because of the administration of contrast material:
      • In people will renal insufficiency
      • In patients with allergy to contrast.[1][2]

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[3]

Continuous-Wave Doppler Ultrasound (DO NOT EDIT)[4]

Class I
"1. Continuous-wave Doppler ultrasound blood flow measurements are useful to provide an accurate assessment of lower extremity PAD location and severity, to follow lower extremity PAD progression, and to provide quantitative follow-up after revascularization procedures. (Level of Evidence: B)"

Contrast Angiography (DO NOT EDIT)[4]

Class I
"1. Contrast angiography provides detailed information about arterial anatomy and is recommended for evaluation of patients with lower extremity PAD when revascularization is contemplated. (Level of Evidence: B)"
"2. A history of contrast reaction should be documented before the performance of contrast angiography and appropriate pretreatment administered before contrast is given. (Level of Evidence: B)"
"3. Decisions regarding the potential utility of invasive therapeutic interventions (percutaneous or surgical) in patients with lower extremity PAD should be made with a complete anatomic assessment of the affected arterial territory, including imaging of the occlusive lesion, as well as arterial inflow and outflow with angiography or a combination of angiography and noninvasive vascular techniques. (Level of Evidence: B)"
"4. Digital subtraction angiography is recommended for contrast angiographic studies because this technique allows for enhanced imaging capabilities compared with conventional unsubtracted contrast angiography. (Level of Evidence: A)"
"5. Before performance of contrast angiography, a full history and complete vascular examination should be performed to optimize decisions regarding the access site, as well as to minimize contrast dose and catheter manipulation. (Level of Evidence: C)"
"6. Selective or superselective catheter placement during lower extremity angiography is indicated because this can enhance imaging, reduce contrast dose, and improve sensitivity and specificity of the procedure. (Level of Evidence: C)"
"7. The diagnostic lower extremity arteriogram should image the iliac, femoral, and tibial bifurcations in profile without vessel overlap. (Level of Evidence: B)"
"8. When conducting a diagnostic lower extremity arteriogram in which the significance of an obstructive lesion is ambiguous, transstenotic pressure gradients and supplementary angulated views should beobtained. (Level of Evidence: B)"
"9. Patients with baseline renal insufficiency should receive hydration before undergoing contrast angiography. (Level of Evidence: B)"
"10. Follow-up clinical evaluation, including a physical examination and measurement of renal function, is recommended within 2 weeks after contrast angiography to detect the presence of delayed adverse effects, such as atheroembolism, deterioration in renal function, or access site injury (e.g., pseudoaneurysm or arteriovenous fistula). (Level of Evidence: C)"
Class IIa
"1. Noninvasive imaging modalities, including MRA, CTA, and color flow duplex imaging, may be used in advance of invasive imaging to develop an individualized diagnostic strategic plan, including assistance in selection of access sites, identification of significant lesions, and determination of the need for invasive evaluation. (Level of Evidence: B)"
"2. Treatment with n-acetylcysteine in advance of contrast angiography is suggested for patients with baseline renal insufficiency (creatinine greater than 2.0 mg per dL). (Level of Evidence: B)"

References

  1. ↑ Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL; et al. (2006). "ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation". J Am Coll Cardiol. 47 (6): 1239–312. doi:10.1016/j.jacc.2005.10.009. PMID 16545667.
  2. ↑ Wennberg PW, Rooke TW. Chapter 109. Diagnosis and Management of Diseases of the Peripheral Arteries and Veins. In: Fuster V, Walsh RA, Harrington RA, eds. Hurst's The Heart. 13th ed. New York: McGraw-Hill; 2011.
  3. ↑ 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.
  4. ↑ 4.0 4.1 Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B (2006). "ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation". Circulation. 113 (11): e463–654. doi:10.1161/CIRCULATIONAHA.106.174526. PMID 16549646. Retrieved 2012-10-09. Unknown parameter |month= ignored (help)


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