- Case report
- Open Access
- Open Peer Review
Contrast stress echocardiography in hypertensive heart disease
© Lønnebakken et al; licensee BioMed Central Ltd. 2011
- Received: 23 September 2011
- Accepted: 18 November 2011
- Published: 18 November 2011
Hypertension is associated with atherosclerosis and cardiac and vascular structural and functional changes. Myocardial ischemia may arise in hypertension independent of coronary artery disease through an interaction between several pathophysiological mechanisms, including left ventricular hypertrophy, increased arterial stiffness and reduced coronary flow reserve associated with microvascular disease and endothelial dysfunction. The present case report demonstrates how contrast stress echocardiography can be used to diagnose myocardial ischemia in a hypertensive patient with angina pectoris but without significant obstructive coronary artery disease. The myocardial ischemia was due to severe resistant hypertension complicated with concentric left ventricular hypertrophy and increased arterial stiffness.
- Myocardial hypoperfusion
- Concentric left ventricular hypertrophy
- Arterial stiffness
Hypertension is associated with atherosclerosis and cardiovascular structural and functional changes predisposing hypertensive patients to myocardial ischemia also in the absence of significant epicardial coronary artery disease through a number of pathophysiological mechanisms. Increased arterial stiffness is common in hypertension, and associated with structural changes in the left ventricle, typically concentric hypertrophy or concentric remodelling [1–3]. Increased arterial stiffness may also contribute to myocardial ischemia as a consequence of the earlier return of reflection waves in stiff arteries and hence a reduction in diastolic myocardial perfusion pressure . The combination of muscle-capillary mismatch due to concentric left ventricular hypertrophy and reduced diastolic myocardial perfusion pressure due to increased arterial stiffness may lead to severe myocardial ischemia. Typically these patients develop myocardial fibrosis with subsequent deterioration of diastolic and systolic function and finally clinical heart failure . In addition, coronary microvascular dysfunction is common in hypertension and contributes to left ventricular ischemia . Recently the diagnostic and prognostic value of Doppler derived coronary flow reserve measurement by vasodilator stress echocardiography was demonstrated . However, myocardial hypoperfusion may also be directly visualized by contrast stress echocardiography . This case report demonstrates the usefulness of including contrast stress echocardiography in multimodality cardiovascular imaging in diagnostic work-up of a patient with refractory hypertension presenting with exercise induced chest pain.
A 42-years old African man was referred for stress echocardiography due to exercise induced chest pain. Clinically he had resistant hypertension based on sitting blood pressure (140/100 mmHg) in spite of treatment with 4 different antihypertensive drugs, including a β-blocker, calcium-blocker, diuretic and angiotensin-2 blocker . Twenty-four hour ambulatory blood pressure was on average 127/85 mmHg, but 39% of systolic and 64% of diastolic measurements were elevated, and the diurnal variation was reduced. Further diagnostic work-up did not reveal any signs of secondary hypertension. His medical history included complete recovery after coiling of a cerebral aneurysm associated with subarachnoid bleeding in 2004. There was a family history of hypertension and the patient had undergone coronary angiography in 2006 which was reported as normal.
Additional file 1: Contrast echocardiography at baseline demonstrating the delayed contrast enhancement, in particularly in the distal part of intraventricular septum in an apical 4-chamber view. (AVI 17 MB)
Additional file 2: Contrast echocardiography at peak dobutamine-atropine stress demonstrating the globally delayed contrast enhancement in apical 4-chamber view. (AVI 12 MB)
This case report demonstrates how contrast stress echocardiography may be used in cardiovascular multimodality imaging work-up of hypertensive patients with chest pain and non-obstructive coronary artery disease. The present patient had symptomatic severe myocardial ischemia documented by contrast echocardiography in the absence of significant angiographic coronary artery disease . Myocardial ischemia was induced through an interaction between non-obstructive coronary artery disease, increased arterial stiffness and concentric left ventricular hypertrophy, three well known types of cardiovascular end-organ damage in hypertension .
Hypertension is recognized as a risk factor for development of atherosclerosis including vascular smooth muscle growth and lengthening of arteries (depicted as tortuous coronary arteries in Figure 4) and endothelial dysfunction . Non-obstructive coronary artery disease is not uncommon in hypertensive patients undergoing coronary angiography due to chest pain, and detection of reduced Doppler derived coronary flow reserve during vasodilator stress echocardiography, reflecting microvascular disease and endothelial dysfunction in such patients, has been shown to predict worse prognosis in spite of normal wall motion score during conventional stress echocardiography [7, 17].
Increased arterial stiffness is a well-known marker of cardiovascular risk and disease in hypertension . Current guidelines recommend assessment of arterial stiffness from carotid-femoral artery pulse wave velocity, and this was high for age in this patient consistent with increased arterial stiffness . The increased stiffness causes refection waves to return earlier to proximal aorta and thereby reduce the myocardial diastolic perfusion pressure. The myocardial diastolic perfusion pressure is of crucial importance to the perfusion of the myocardium, particularly during exercise, due to increased heart rate and hence shortening of the diastole.
Concentric left ventricular hypertrophy is the prognostically most unfavourable geometric pattern found in hypertension and particularly common in hypertensive patients of African origin . Hypertension increases the left ventricular workload and thereby the oxygen demands of the myocardium. In particular concentric hypertrophy is also associated with a muscle-capillary mismatch as well as high endocardial wall stress which may contribute to the diagnosed myocardial ischemia in our patient . Chronic ischemia may promote structural changes in the myocardium and development of fibrosis that together with functional myocardial impairment due to ischemia induced metabolic changes causes heart failure, the end stage of hypertensive heart disease.
Contrast stress echocardiography is particularly suited to detect myocardial ischemia. In accordance with current guidelines a contrast agent should be added during stress echocardiography when 2 or more left ventricular segments cannot be sufficiently evaluated [19, 20]. This does not only improve wall motion assessment  but allows simultaneous evaluation of myocardial ischemia as contrast microbubbles are isolated intravascular tracers directly reflecting myocardial perfusion and capillary density . Even if direct quantification of myocardial perfusion has proven difficult so far, qualitative detection of delayed contrast enhancement has been shown to be more sensitive to detect coronary artery disease than wall motion alone . As ultrasound contrast often is indicated due to image quality, simultaneous assessment of myocardial perfusion adds important information on regional myocardial ischemia with high spatial resolution without extra cost. Furthermore, the safety of contrast echocardiography and potential side effects are well documented .
Also in hypertensive patients, development of wall motion abnormalities during stress echocardiography is associated with increased cardiovascular event rate . Hypertension is associated with both increased prevalence of severe coronary artery disease as well as increased prevalence of non-obstructive ischemic heart disease. Echocardiographic diagnosis of microvascular disease should not be made unless obstructive coronary artery disease has been ruled out by coronary angiography or coronary computer tomographic angiography [22, 23]. Diagnosis of non-obstructive ischemic heart disease is challenging and requires use of multimodality imaging as demonstrated by the present case. In particular vasodilation stress echocardiography assessing coronary flow reserve and myocardial perfusion assessment by contrast stress echocardiography or magnetic resonance imaging have proven useful in diagnosis of non-obstructive ischemic heart disease, while this diagnosis may often be missed on conventional stress echocardiography assessing only wall motion abnormality [7, 22, 23]. Coronary flow reserve <1.91 during adenosine stress has been associated with increased cardiovascular risk in hypertensive patients independent of the presence of wall motion abnormalities . Furthermore, a coronary computer tomographic angiography study recently documented reduced prognosis in women with non-obstructive ischemic heart disease . Therefore, diagnosing symptomatic myocardial ischemia in hypertensive patients without significant coronary artery disease has important clinical implications and should initiate aggressive anti-hypertensive and anti-ischemic treatment as well as risk factor modification to improve symptoms and prognosis. In particular, performing 24 hour ambulatory blood pressure recording for optimal assessment of blood pressure is important in resistant hypertension. Improved blood pressure control in resistant hypertension may be obtained by adding a small dosage of an aldosterone blocker or amiloride, the latter particularly effective in hypertension in Africans . Furthermore, treatment with angiotensin converting enzyme inhibitors or statins improves microvascular function and symptoms in non-obstructive ischemic heart disease .
Chronic uncontrolled hypertension is associated with development of cardiovascular complications including atherosclerosis, left ventricular hypertrophy, arterial stiffening and microvascular dysfunction. This can cause symptomatic myocardial ischemia even in the absence of significant epicardial coronary artery stenoses. In hypertensive patients with exercise induced chest pain and non-obstructive coronary artery disease, additional multimodality imaging including contrast stress echocardiography and assessment of vascular function is useful to identify the cause of symptoms and optimally manage such patients.
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
We want to thank Britt Gjellefall for assessment of vascular function.
- de Simone G, Roman MJ, Koren MJ, Mensah GA, Ganau A, Devereux RB: Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension. Hypertension. 1999, 33 (3): 800-805.View ArticlePubMedGoogle Scholar
- Schillaci G, Mannarino MR, Pucci G, Pirro M, Helou J, Savarese G, Vaudo G, Mannarino E: Age-specific relationship of aortic pulse wave velocity with left ventricular geometry and function in hypertension. Hypertension. 2007, 49 (2): 317-321.View ArticlePubMedGoogle Scholar
- Antonini-Canterin F, Carerj S, Di B, Di SG, La CS, Vriz O, Pavan D, Balbarini A, Nicolosi GL: Arterial stiffness and ventricular stiffness: a couple of diseases or a coupling disease? A review from the cardiologist's point of view. Eur J Echocardiogr. 2009, 10 (1): 36-43. 10.1093/ejechocard/jen236.View ArticlePubMedGoogle Scholar
- Laurent S, Cockcroft J, Van BL, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H: Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006, 27 (21): 2588-2605. 10.1093/eurheartj/ehl254.View ArticlePubMedGoogle Scholar
- Shantsila A, Dwivedi G, Shantsila E, Butt M, Beevers DG, Lip GY: Persistent macrovascular and microvascular dysfunction in patients with malignant hypertension. Hypertension. 2011, 57 (3): 490-496. 10.1161/HYPERTENSIONAHA.110.166314.View ArticlePubMedGoogle Scholar
- Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, Tramontana S, Perticone F, Naccarato P, Picano E, Cortigiana L, Bevilacqua M, Milazzo L, Crusi D, Barlassina C, Sarzi-Puttini P, Turiel M: From endothelial dysfunction to atherosclerosis. Autoimmun Rev. 2010, 9: 830-834. 10.1016/j.autrev.2010.07.016.View ArticlePubMedGoogle Scholar
- Cortigani L, Rigo F, Galderisi M, Gherardi S, Bovenzi F, Picano E, Sicari R: Diagnostic and prognostic value of Doppler echocardiographic coronary flow reserve in the left anterior descending artery. Heart. 2011, 97: 1758-1765. 10.1136/heartjnl-2011-300178.View ArticleGoogle Scholar
- Lønnebakken MT, Gerdts E: Impact of ultrasound contrast agents in echocardiographic assessment of ischemic heart disease. Recent Pat Cardiovasc Drug Discov. 2010, pii: 645193Google Scholar
- Mancia G, De BG, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De CR, Dean V, et al: 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007, 25 (6): 1105-1187. 10.1097/HJH.0b013e3281fc975a.View ArticlePubMedGoogle Scholar
- Haykowsky M, Taylor D, Teo K, Quinney A, Humen D: Left ventricular wall stress during leg-press exercise performed with a brief Valsalva maneuver. Chest. 2001, 119 (1): 150-154. 10.1378/chest.119.1.150.View ArticlePubMedGoogle Scholar
- Kidawa M, Coignard L, Drobinski G, Krzeminska-Pakula M, Thomas D, Komajda M, Isnard R: Comparative value of tissue Doppler imaging and m-mode color Doppler mitral flow propagation velocity for the evaluation of left ventricular filling pressure. Chest. 2005, 128 (4): 2544-2550. 10.1378/chest.128.4.2544.View ArticlePubMedGoogle Scholar
- Circulatory variables measured by invasive techniques. Definitions, abbreviations, units, methods of measurements and normal values. A report of the WHO/IFSC Task Force on Haemodynamics. Eur Heart J. 1985, 6 (Suppl C): 1-50.Google Scholar
- Agabiti-Rosei E, Mancia G, O'Rourke MF, Roman MJ, Safar ME, Smulyan H, Wang JG, Wilkinson IB, Williams B, Vlachopoulos C: Central blood pressure measurements and antihypertensive therapy: a consensus document. Hypertension. 2007, 50 (1): 154-160. 10.1161/HYPERTENSIONAHA.107.090068.View ArticlePubMedGoogle Scholar
- Mattace-Raso FU, Hofman A, Verwoert GC, Wittemana JC, Wilkenson I, Cockcroft J, McEniery C, Laurent S, Boutouyrie P, Bozec E, Hansen TW, Torp-Pedersen C, Ibsen H, Jeppesen J, Vermeersch SJ, Rietzschel E, De Buyzere M, Gillebert TC, Van Bortel L, Segers P, et al: Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'establishing normal and reference values'. Eur Heart J. 2010, 31 (19): 2338-2350.View ArticleGoogle Scholar
- Lønnebakken MT, Staal EM, Nordrehaug J, Gerdts E: Usefulness of contrast echocardiography for predicting the severity of angiographic coronary disease in non-ST elevation myocardial infarction. Am J Cardiol. 2011, 107: 1262-1267. 10.1016/j.amjcard.2010.12.034.View ArticlePubMedGoogle Scholar
- Nilsson PM, Boutouyrie P, Laurent S: Vascular aging: A tale of EVA and ADAM in cardiovascular risk assessment and prevention. Hypertension. 2009, 54 (1): 3-10. 10.1161/HYPERTENSIONAHA.109.129114.View ArticlePubMedGoogle Scholar
- Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN: Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010, 55 (25): 2825-2832. 10.1016/j.jacc.2010.01.054.View ArticlePubMedPubMed CentralGoogle Scholar
- Gerdts E, Cramariuc D, de SG, Wachtell K, Dahlof B, Devereux RB: Impact of left ventricular geometry on prognosis in hypertensive patients with left ventricular hypertrophy (the LIFE study). Eur J Echocardiogr. 2008, 9 (6): 809-815. 10.1093/ejechocard/jen155.View ArticlePubMedGoogle Scholar
- Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG: American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr. 2007, 20 (9): 1021-1041. 10.1016/j.echo.2007.07.003.View ArticlePubMedGoogle Scholar
- Senior R, Becher H, Monaghan M, Agati L, Zamorano J, Vanoverschelde JL, Nihoyannopoulos P: Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography. Eur J Echocardiogr. 2009, 10 (2): 194-212.View ArticlePubMedGoogle Scholar
- Lønnebakken MT, Bleie O, Strand E, Staal EM, Nygård OK, Gerdts E: Myocardial contrast echocardiography in assessment of stable coronary artery disease at intermediate dobutamine-induced stress level. Echocardiogr. 2009, 26: 52-60. 10.1111/j.1540-8175.2008.00738.x.View ArticleGoogle Scholar
- Cortigani L, Paolini EA, Nannini E: Dipyridamol stress echocardiography for risk stratification in hypertensive patients with chest pain. Circulation. 1998, 98: 2855-9.View ArticleGoogle Scholar
- Gerbaud E, Harcaut E, Coste P, Erickson M, Lederlin M, Labêque JN, Perron JM, Cochet H, Dos Santos P, Durrieu-Jais C, Laurent F, Montaudon M: Cardiac magnetic resonance imaging for the diagnosis of patients presenting with chest pain, raised troponin, and unobstructed coronary arteries. Int J Cardiovasc Imaging. 2011, PMID: 21538065Google Scholar
- Shaw LJ, Min JK, Narula J, Lin F, Bairey-Merz N, Callister TQ, Berman DS: Sex differences in mortality associated with computed tomographic angiographic measurements of obstructive and nonobstructive coronary artery disease: An exploratory analysis. Circ Cardiovasc Imaging. 2010, 3: 473-481. 10.1161/CIRCIMAGING.109.860981.View ArticlePubMedGoogle Scholar
- Pizzi C, Manfrini O, Fontana F, Bugiardini R: Angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme A reductase in cardiac Syndrome X: role of superoxide dismutase activity. Circulation. 2004, 109: 53-58. 10.1161/01.CIR.0000116209.25597.AE.View ArticlePubMedGoogle Scholar
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