- Email: [email protected]
Resistant Hypertension
IMAGES IN RADIOLOGY Robert G. Stern, MD, Section Editor
Resistant Hypertension Simone Romano, MD,a,b Satish J. Chacko, MD,a Vibhav Rangarajan, MD,a Jaehoon Chung, MD,a Afshin Farzaneh-Far, MD, PhDa,c a
Section of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago; bDepartment of Internal Medicine, University of Verona, Italy; cDivision of Cardiology, Department of Medicine, Duke University, Durham, NC.
PRESENTATION A 20-year-old man with resistant hypertension despite treatment with multiple antihypertensive agents was referred for further evaluation.
ASSESSMENT On physical examination, blood pressure was 170/100 mm Hg in both arms with significant radial-femoral pulse delay. Auscultation reveled an aortic ejection click associated with a systolic murmur heard loudest on the back, in the midscapular region.
Usually, the condition is diagnosed in infancy. However, in a number of patients the diagnosis is made first in early adulthood. Although many patients are asymptomatic, some have nonspecific symptoms, such as epistaxis, headache, or leg weakness on exertion. Others may present with more serious symptoms related to congestive heart failure from chronically increased afterload, angina from premature coronary artery disease, aortic valve stenosis or regurgitation from coexisting bicuspid aortic valve disease, aortic dissection, intracerebral hemorrhage, or endocarditis at the coarctation site. On physical examination, these patients classically display hypertension and a systolic murmur associated with radial-femoral pulse delay and diminished lower-extremity
DIAGNOSIS Three-dimensional contrast-enhanced magnetic resonance angiography showed significant focal aortic coarctation, just beyond the origin of the left subclavian artery (Figure 1 and Online Video 1). Coarctation is a vascular disease with narrowing of the aorta and is a common congenital malformation, accounting for up to approximately 1 in 2500 live births.1,2 It can be classified anatomically on the basis of its location relative to the fetal ductus arteriousus as preductal, juxtaductal, or postductal. The postductal and juxtaductal types are the most common forms seen in adults. The majority of patients (50%-85%) have associated bicuspid aortic valve disease, as in this case (Figure 2 and Online Video 2) with an associated aortic ejection click on physical examination.
Funding: JC was funded by National Institutes of Health Training Grant T32HL072742. Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Afshin Farzaneh-Far, MD, PhD, University of Illinois at Chicago, Section of Cardiology, 840 South Wood St M/C 715, Suite 920 S, Chicago, IL 60612. E-mail address: [email protected]
0002-9343/$ -see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjmed.2015.05.008
Figure 1 Three-dimensional contrast-enhanced magnetic resonance angiography with volume-rendering technique showing significant focal aortic coarctation (red arrow) just beyond the origin of the left subclavian artery (blue arrow). A few collateral vessels are also present (white arrows).
e24
The American Journal of Medicine, Vol 128, No 10, October 2015 important anatomic and physiologic information, including aortic morphology and dimensions, as well as assessment of severity by providing pressure gradients and collateral flow measurements.3
MANAGEMENT
Figure 2 Single cardiac magnetic resonance cine image showing the aortic valve en face. The valve is bicuspid with fusion of the left and right cusps (blue arrow). The noncoronary cusp is shown with a red arrow. The open valve orifice is shown with a black arrow. There is no significant stenosis or regurgitation at this time.
pulses. Relative renal hypoperfusion leads to neurohormonal and vascular changes resulting in compensatory increases in upper-extremity blood pressure.2 Over time, collateral vessels may develop between the upper and lower descending aorta (Figure 1, white arrows) as a way to bypass the coarctation and maintain lower body blood flow. Collateral vessels often develop through the subclavian artery, forming a pathway via the internal mammary and intercostal arteries into the descending thoracic aorta, resulting in a continuous murmur that extends into diastole. Collateral vessels sometimes can be seen on close inspection of the upper chest, scapulae, and shoulders. The dilated and tortuous intercostal arteries erode the inferior margins of the ribs, resulting in the classic “rib-notching” pattern seen on chest radiography. In some cases, a “figure of 3” sign also may be seen on the left upper border of the mediastinum on the chest x-ray, formed by prestenotic dilatation, indentation at the coarctation site, and poststenotic dilatation of the descending aorta. Echocardiography may show left ventricular hypertrophy and coexisting bicuspid aortic valve disease and may allow an initial assessment of coarctation severity by measuring peak descending aortic blood flow velocities with Doppler imaging. Invasive cardiac catheterization often is used to assess coarctation severity; however, it is important to emphasize that significant collateral flow may “mask” the severity of the obstruction, as measured by pressure gradients because only a portion of blood flow actually traverses the obstruction.3,4 Magnetic resonance imaging has emerged as a powerful tool for comprehensively assessing these patients, providing
Treatment of hypertension is paramount, because aortic coarctation is associated with accelerated coronary artery disease, aneurysms of the circle of Willis, and aortic dissection. The average age of death for an adult with unrepaired isolated aortic coarctation is 35 years.2-4 Because hypertension is at least partly due to mechanical obstruction, patients are refractory to pharmacologic therapy. Therefore, generally, stenting or surgical repair is recommended, resulting in blood pressure improvements and decreased antihypertensive medication requirements.4-6 However, hypertension persists or reoccurs in a significant number of individuals for unclear reasons, perhaps related to abnormalities of the vascular bed proximal to the coarctation.5-7 Indeed, it has been shown that normotensive children and young adults who have undergone successful coarctation repair have persistent endothelial dysfunction and impaired arterial reactivity, suggesting the presence of intrinsic vascular abnormalities in this condition.8,9 Thus, although coarctation of the aorta was regarded initially as a localized abnormality, it is now thought to be a diffuse arteriopathy and part of the spectrum of pathology associated with bicuspid aortic valve disease (Figure 2 and Online Video 2, available online), which can progress to significant valvular stenosis or regurgitation, as well as aortic enlargement and dissection.10
CONCLUSIONS Patients with repaired aortic coarctation should never be considered “cured,” and life expectancy remains reduced. Therefore, they require continued close follow-up for hypertension, recoarctation, aortic valve dysfunction, premature coronary artery disease, aortic dilation, dissection, and other complications.4,5,7
References 1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890-1900. 2. Rhodes JF, Hijazi ZM, Sommer RJ. Pathophysiology of congenital heart disease in the adult, part II: simple obstructive lesions. Circulation. 2008;117:1228-1237. 3. Nielsen JC, Powell AJ, Gauvreau K, Marcus EN, Prakash A, Geva T. Magnetic resonance imaging predictors of coarctation severity. Circulation. 2005;111:622-628. 4. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease. J Am Coll Cardiol. 2008;52:e143-263. 5. Celermajer DS, Greaves K. Survivors of coarctation repair: fixed but not cured. Heart. 2012;88:113-114. 6. Chen SSM, Donald AE, Storry C, Halcox JP, Bonhoeffer P, Deanfield JE. Impact of aortic stenting on peripheral vascular function and daytime systolic blood pressure in adult coarctation. Heart. 2008;94:919-924.
Romano et al
Resistant Hypertension
7. Oechslin EN. Does a stent cure hypertension? Heart. 2008;94: 828-829. 8. Brili S, Tousoulis D, Antoniades C, et al. Evidence of vascular dysfunction in young patients with successfully repaired coarctation of aorta. Atherosclerosis. 2005;182:97-103. 9. Gardiner HM, Celermajer DS, Sorensen KE, et al. Arterial reactivity is significantly impaired in normotensive young adults after successful repair of aortic coarctation in childhood. Circulation. 1994;89: 1745-1750.
e25 10. Warnes CA. Bicuspid aortic valve and coarctation: two villains part of a diffuse problem. Heart. 2003;89:965-966.
SUPPLEMENTARY DATA Supplementary videos accompanying this article can be found in the online version at http://dx.doi.org/10.1016/ j.amjmed.2015.05.008.
Resistant Hypertension Simone Romano, MD,a,b Satish J. Chacko, MD,a Vibhav Rangarajan, MD,a Jaehoon Chung, MD,a Afshin Farzaneh-Far, MD, PhDa,c a
Section of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago; bDepartment of Internal Medicine, University of Verona, Italy; cDivision of Cardiology, Department of Medicine, Duke University, Durham, NC.
PRESENTATION A 20-year-old man with resistant hypertension despite treatment with multiple antihypertensive agents was referred for further evaluation.
ASSESSMENT On physical examination, blood pressure was 170/100 mm Hg in both arms with significant radial-femoral pulse delay. Auscultation reveled an aortic ejection click associated with a systolic murmur heard loudest on the back, in the midscapular region.
Usually, the condition is diagnosed in infancy. However, in a number of patients the diagnosis is made first in early adulthood. Although many patients are asymptomatic, some have nonspecific symptoms, such as epistaxis, headache, or leg weakness on exertion. Others may present with more serious symptoms related to congestive heart failure from chronically increased afterload, angina from premature coronary artery disease, aortic valve stenosis or regurgitation from coexisting bicuspid aortic valve disease, aortic dissection, intracerebral hemorrhage, or endocarditis at the coarctation site. On physical examination, these patients classically display hypertension and a systolic murmur associated with radial-femoral pulse delay and diminished lower-extremity
DIAGNOSIS Three-dimensional contrast-enhanced magnetic resonance angiography showed significant focal aortic coarctation, just beyond the origin of the left subclavian artery (Figure 1 and Online Video 1). Coarctation is a vascular disease with narrowing of the aorta and is a common congenital malformation, accounting for up to approximately 1 in 2500 live births.1,2 It can be classified anatomically on the basis of its location relative to the fetal ductus arteriousus as preductal, juxtaductal, or postductal. The postductal and juxtaductal types are the most common forms seen in adults. The majority of patients (50%-85%) have associated bicuspid aortic valve disease, as in this case (Figure 2 and Online Video 2) with an associated aortic ejection click on physical examination.
Funding: JC was funded by National Institutes of Health Training Grant T32HL072742. Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Afshin Farzaneh-Far, MD, PhD, University of Illinois at Chicago, Section of Cardiology, 840 South Wood St M/C 715, Suite 920 S, Chicago, IL 60612. E-mail address: [email protected]
0002-9343/$ -see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjmed.2015.05.008
Figure 1 Three-dimensional contrast-enhanced magnetic resonance angiography with volume-rendering technique showing significant focal aortic coarctation (red arrow) just beyond the origin of the left subclavian artery (blue arrow). A few collateral vessels are also present (white arrows).
e24
The American Journal of Medicine, Vol 128, No 10, October 2015 important anatomic and physiologic information, including aortic morphology and dimensions, as well as assessment of severity by providing pressure gradients and collateral flow measurements.3
MANAGEMENT
Figure 2 Single cardiac magnetic resonance cine image showing the aortic valve en face. The valve is bicuspid with fusion of the left and right cusps (blue arrow). The noncoronary cusp is shown with a red arrow. The open valve orifice is shown with a black arrow. There is no significant stenosis or regurgitation at this time.
pulses. Relative renal hypoperfusion leads to neurohormonal and vascular changes resulting in compensatory increases in upper-extremity blood pressure.2 Over time, collateral vessels may develop between the upper and lower descending aorta (Figure 1, white arrows) as a way to bypass the coarctation and maintain lower body blood flow. Collateral vessels often develop through the subclavian artery, forming a pathway via the internal mammary and intercostal arteries into the descending thoracic aorta, resulting in a continuous murmur that extends into diastole. Collateral vessels sometimes can be seen on close inspection of the upper chest, scapulae, and shoulders. The dilated and tortuous intercostal arteries erode the inferior margins of the ribs, resulting in the classic “rib-notching” pattern seen on chest radiography. In some cases, a “figure of 3” sign also may be seen on the left upper border of the mediastinum on the chest x-ray, formed by prestenotic dilatation, indentation at the coarctation site, and poststenotic dilatation of the descending aorta. Echocardiography may show left ventricular hypertrophy and coexisting bicuspid aortic valve disease and may allow an initial assessment of coarctation severity by measuring peak descending aortic blood flow velocities with Doppler imaging. Invasive cardiac catheterization often is used to assess coarctation severity; however, it is important to emphasize that significant collateral flow may “mask” the severity of the obstruction, as measured by pressure gradients because only a portion of blood flow actually traverses the obstruction.3,4 Magnetic resonance imaging has emerged as a powerful tool for comprehensively assessing these patients, providing
Treatment of hypertension is paramount, because aortic coarctation is associated with accelerated coronary artery disease, aneurysms of the circle of Willis, and aortic dissection. The average age of death for an adult with unrepaired isolated aortic coarctation is 35 years.2-4 Because hypertension is at least partly due to mechanical obstruction, patients are refractory to pharmacologic therapy. Therefore, generally, stenting or surgical repair is recommended, resulting in blood pressure improvements and decreased antihypertensive medication requirements.4-6 However, hypertension persists or reoccurs in a significant number of individuals for unclear reasons, perhaps related to abnormalities of the vascular bed proximal to the coarctation.5-7 Indeed, it has been shown that normotensive children and young adults who have undergone successful coarctation repair have persistent endothelial dysfunction and impaired arterial reactivity, suggesting the presence of intrinsic vascular abnormalities in this condition.8,9 Thus, although coarctation of the aorta was regarded initially as a localized abnormality, it is now thought to be a diffuse arteriopathy and part of the spectrum of pathology associated with bicuspid aortic valve disease (Figure 2 and Online Video 2, available online), which can progress to significant valvular stenosis or regurgitation, as well as aortic enlargement and dissection.10
CONCLUSIONS Patients with repaired aortic coarctation should never be considered “cured,” and life expectancy remains reduced. Therefore, they require continued close follow-up for hypertension, recoarctation, aortic valve dysfunction, premature coronary artery disease, aortic dilation, dissection, and other complications.4,5,7
References 1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890-1900. 2. Rhodes JF, Hijazi ZM, Sommer RJ. Pathophysiology of congenital heart disease in the adult, part II: simple obstructive lesions. Circulation. 2008;117:1228-1237. 3. Nielsen JC, Powell AJ, Gauvreau K, Marcus EN, Prakash A, Geva T. Magnetic resonance imaging predictors of coarctation severity. Circulation. 2005;111:622-628. 4. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease. J Am Coll Cardiol. 2008;52:e143-263. 5. Celermajer DS, Greaves K. Survivors of coarctation repair: fixed but not cured. Heart. 2012;88:113-114. 6. Chen SSM, Donald AE, Storry C, Halcox JP, Bonhoeffer P, Deanfield JE. Impact of aortic stenting on peripheral vascular function and daytime systolic blood pressure in adult coarctation. Heart. 2008;94:919-924.
Romano et al
Resistant Hypertension
7. Oechslin EN. Does a stent cure hypertension? Heart. 2008;94: 828-829. 8. Brili S, Tousoulis D, Antoniades C, et al. Evidence of vascular dysfunction in young patients with successfully repaired coarctation of aorta. Atherosclerosis. 2005;182:97-103. 9. Gardiner HM, Celermajer DS, Sorensen KE, et al. Arterial reactivity is significantly impaired in normotensive young adults after successful repair of aortic coarctation in childhood. Circulation. 1994;89: 1745-1750.
e25 10. Warnes CA. Bicuspid aortic valve and coarctation: two villains part of a diffuse problem. Heart. 2003;89:965-966.
SUPPLEMENTARY DATA Supplementary videos accompanying this article can be found in the online version at http://dx.doi.org/10.1016/ j.amjmed.2015.05.008.