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| {{Chronic stable angina}} | | __NOTOC__ |
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| {{CMG}} | | {{CMG}} |
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| ''The terms '''Syndrome X''' or '''Metabolic syndrome X''' may also be referring to [[metabolic syndrome]].''
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| '''''Synonyms and key words:''''' Microvascular angina
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| ==Overview== | | ==Overview== |
| '''(Cardiac) syndrome X''' is [[Angina pectoris|angina]] (chest pain) associated with objective evidence of myocardial ischemia in the absence of epicardial [[coronary artery disease]]. The disorder has been hypothesized to be a disorder of the coronary microvasculature rather than the large caliber epicardial coronary arteries.
| | Syndrome X may refer to [[cardiac syndrome X]], [[metabolic syndrome]] and single X syndrome, where an individual has a single X chromosome, typically described as [[Turner syndrome]]. The otherwise unidentifiable rare disease afflicting [[Brooke Greenberg]] and only about half a dozen other people in the world. |
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| ==Pathophysiology==
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| In a large percentage of patients, there is coronary microvascular dysfunction. Specifically, the microvasculature cannot dilate to accomadate increased blood flow during exertion to meet the needs of myocardial metabolism. There does not appear to be a systemic abnormality in vasomotor function as brachial artery reactivity is normal<ref name="pmid8712140">Bøtker HE, Sonne HS, Sørensen KE (1996) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8712140 Frequency of systemic microvascular dysfunction in syndrome X and in variant angina.] ''Am J Cardiol'' 78 (2):182-6. PMID: [http://pubmed.gov/8712140 8712140]</ref>.
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| Most likely the underlying pathophysiology is heterogenous, and multiple pathophysiologic mechanisms have been proposed with variable data to support them:
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| ===Ischemia is Present in Syndrome X===
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| It has been debated as to whether ischemia is present in patients with Syndrome X. There may be no wall motion abnormalities or coronary sinus lactate production during an episode of ischemic discomfort. This may be due to focal involvement of the myocardium. When [[coronary sinus]] samples of more sensitive markers of ischemia reperfusion / oxidative stress are analyzed such as lipid hydroperoxides (ROOHs) and conjugated dienes (CDs) before and after pacing, there is an increase in ROOH and CD levels (from 4.83 +/- 1.18 micromol/l at baseline to 7.88 +/- 1.12 micromol/l and from 0.038 +/- 0.002 to 0.051 +/- 0.003 arbitrary units, respectively, P < 0.01)<ref name="pmid11087214">Buffon A, Rigattieri S, Santini SA, Ramazzotti V, Crea F, Giardina B et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11087214 Myocardial ischemia-reperfusion damage after pacing-induced tachycardia in patients with cardiac syndrome X.] ''Am J Physiol Heart Circ Physiol'' 279 (6):H2627-33. PMID: [http://pubmed.gov/11087214 11087214]</ref>. In contrast, ROOH and CD levels did not increase in control patients after pacing.
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| ===Adenosine as a Cause of Chest Pain===
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| Both endogenous and exogenous adenosine can cause chest discomfort through stimulation of sensory nerves in the heart <ref>http://www.nejm.org/doi/full/10.1056/NEJM200210243471717</ref><ref name="pmid7544544">{{cite journal| author=Huang MH, Sylvén C, Horackova M, Armour JA| title=Ventricular sensory neurons in canine dorsal root ganglia: effects of adenosine and substance P. | journal=Am J Physiol | year= 1995 | volume= 269 | issue= 2 Pt 2 | pages= R318-24 | pmid=7544544 | doi= | pmc= | url= }} </ref>. Huang et al have demonstrated that both A1- and A2-adenosine receptors are present on the cardiac sensory nerve endings of [[dorsal root ganglion]] neurons. These sensory neurons are active in the absence of ischemia, but become further activated during myocardial [[ischemia]]<ref name="pmid7544544">{{cite journal| author=Huang MH, Sylvén C, Horackova M, Armour JA| title=Ventricular sensory neurons in canine dorsal root ganglia: effects of adenosine and substance P. | journal=Am J Physiol | year= 1995 | volume= 269 | issue= 2 Pt 2 | pages= R318-24 | pmid=7544544 | doi= | pmc= | url= }} </ref>. In one study in which adenosine was infused, 95% of patients with Syndrome X had [[chest pain]] whereas only 40% of control patients experienced [[chest pain]] (p<0.001) <ref name="pmid12075055">{{cite journal| author=Panting JR, Gatehouse PD, Yang GZ, Grothues F, Firmin DN, Collins P et al.| title=Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 25 | pages= 1948-53 | pmid=12075055 | doi=10.1056/NEJMoa012369 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12075055 }} </ref>
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| ===An Extension of Dysautonomias===
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| Syndrome X has been associated with [[dysautonomias]] and with a greater frequency of autonomic symptoms such as [[tachycardia]], [[dyspnea]], [[dizziness]], and [[paresthesias]] <ref name="pmid3337115">{{cite journal| author=Katon W, Hall ML, Russo J, Cormier L, Hollifield M, Vitaliano PP et al.| title=Chest pain: relationship of psychiatric illness to coronary arteriographic results. | journal=Am J Med | year= 1988 | volume= 84 | issue= 1 | pages= 1-9 | pmid=3337115 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3337115 }} </ref>. It has therefore been hypothesized that Syndrome X may be an extension of abnormalities of the autonomic nervous system.
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| ==="Female Pattern" of Atherosclerosis===
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| It has also been speculated that although the coronary arteriogram may appear normal, there may in fact be diffuse atherosclerosis present in what has been termed "a female pattern" of disease.
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| ===Enhanced Pain Sensitivity===
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| Patients with normal coronary arteries and myocardial ischemia have a lower pain threshold and a lower tolerance to pain induced by adenosine <ref name="pmid1389759">{{cite journal| author=Lagerqvist B, Sylvén C, Waldenström A| title=Lower threshold for adenosine-induced chest pain in patients with angina and normal coronary angiograms. | journal=Br Heart J | year= 1992 | volume= 68 | issue= 3 | pages= 282-5 | pmid=1389759 | doi= | pmc=PMC1025071 | url= }} </ref>.
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| ===Panic Disorder===
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| Approximately one third of patients with [[angina pectoris]] and normal coronary arteries are diagnosed with [[panic disorder]] <ref name="pmid3565851">{{cite journal| author=Mukerji V, Beitman BD, Alpert MA, Lamberti JW, DeRosear L, Basha IM| title=Panic disorder: a frequent occurrence in patients with chest pain and normal coronary arteries. | journal=Angiology | year= 1987 | volume= 38 | issue= 3 | pages= 236-40 | pmid=3565851 | doi= | pmc= | url= }} </ref>.
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| ==Epidemiology and Demographics==
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| Syndrome X occurs more often in women. 61.5% of women with Syndrome X are postmenopausal at the time of onset<ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>. Some studies have found an increased risk of other vasospastic disorders in syndrome X patients, such as [[migraine]] and [[Raynaud's phenomenon]].
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| ==Natural history, complications, and prognosis==
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| Syndrome X does not appear to be associated with an excess of major coronary events. In a longitudinal study of 99 patients with Syndorme X over 7 +/- 4 years, left ventricular function was stable: fractional shortening at baseline was 35.4 +/- 4% vs. 35.6 +/- 3% at follow-up and [[congestive heart failure]] developed in only one patient<ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>. Symptoms did not change in about tho thirds of patients, they improved in 10% of patients, and they were worse in about a quarter of patients <ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>
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| The absence of significant coronary artery disease on coronary angiography is associated with a good prognosis. Among 3,136 patients with normal angiograms, the 7 year survival rate was 96%<ref name="pmid3512658">{{cite journal| author=Kemp HG, Kronmal RA, Vlietstra RE, Frye RL| title=Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study. | journal=J Am Coll Cardiol | year= 1986 | volume= 7 | issue= 3 | pages= 479-83 | pmid=3512658 | doi= | pmc= | url= }} </ref>.
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| ==Risk Factors==
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| Female gender and [[left ventricular hypertrophy]] are associated with an excess risk of Syndrome X. The onset in women often occurs after [[menopause]]<ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>. Syndrome X and its accompanying microvascular dysfunction are not associated with traditional cardiovascular risk factors <ref name="pmid21135582">{{cite journal| author=Sestito A, Lanza GA, Di Monaco A, Lamendola P, Careri G, Tarzia P et al.| title=Relation between cardiovascular risk factors and coronary microvascular dysfunction in cardiac syndrome X. | journal=J Cardiovasc Med (Hagerstown) | year= 2011 | volume= 12 | issue= 5 | pages= 322-7 | pmid=21135582 | doi=10.2459/JCM.0b013e3283406479 | pmc= | url= }} </ref>. Syndrome X has been associated with elevations of inflammatory markers such as [[C reactive protein]] and soluble [[CD40 ligand]] <ref name="pmid20980002">{{cite journal| author=Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P, Gomez MA, Kaski JC| title=Elevated circulating soluble form of CD40 ligand in patients with cardiac syndrome X. | journal=Atherosclerosis | year= 2010 | volume= 213 | issue= 2 | pages= 637-41 | pmid=20980002 | doi=10.1016/j.atherosclerosis.2010.09.031 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20980002 }} </ref>.
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| ==Other Conditions to Distinguish Syndrome X From==
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| Syndrome X should be distinguished from [[Prinzmetal's angina]], a disorder which involves spasm of the main epicardial coronary arteries. Syndrome X involves dysfunction of the downstream microvasculature. Syndrome X must also be distinguished from [[esophageal spasm]].
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| ==Diagnosis==
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| ===Symptoms===
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| All 99 patients with Syndrome X in one study had exertional angina, and 41 of them had angina at rest<ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>. In patients with syndrome X, the anginal pain tends to last longer after cessation of exertion (> 10 minutes in 53% of patients<ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>) than is typical of patients with fixed obstructions of the epicardial arteries (pain generally lasts 2 to 5 minutes). Sublingual nitroglycerine is often not as effective in the patient with Syndrome X as it is in the patient with obstructive epicardial disease, with only 42% of patients reporting relief <ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>.
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| ===Ambulatory Holter Monitoring===
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| Approximately two thirds of patients (64/99 in one study) will experience ST segment depression on ambulatory Holter monitoring<ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>.
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| ===Cardiac Magnetic Resonance Imaging (CMR)===
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| While there is no difference between control patients and patients with Syndrome X in subepicardial perfusion, there is a greater relative magnitude of subendocardial hypoperfusion on CMR during adenosine infusion in patients with Syndrome X. As a result, "the ratio of subendocardial to subepicardial myocardial-perfusion reserve index is significantly lower in patients with syndrome X". <ref name="pmid12075055">{{cite journal| author=Panting JR, Gatehouse PD, Yang GZ, Grothues F, Firmin DN, Collins P et al.| title=Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 25 | pages= 1948-53 | pmid=12075055 | doi=10.1056/NEJMoa012369 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12075055 }} </ref>.
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| ===Diagnostic Studies and Criteria for Diagnosis===
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| Syndrome X is often a diagnosis of exclusion. The diagnostic criteria are as follows:
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| *There must be evidence of [[myocardial ischemia]]: Diagnostic studies include an exercise [[ECG]], [[stress scintigraphy]], or [[stress echocardiography]] in conjunction with anginal chest discomfort.
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| * [[Angina pectoris|Angina]]: Angina pectoris must be present. The angina pectoris associated with Syndrome X may last longer that the anginal discomfort associated with the fixed epicardial stenoses of atherosclerotic heart disease.
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| * [[Coronary angiogram]]: There is no narrowing of the epicardial arteries. However, Syndrome X may be associated with a reduction in coronary [[vasodilator reserve]] presumably due to abnormalities in the [[coronary microcirculation]]. During stress, sampling of the [[coronary sinus]] may demonstrate the production of [[lactate]] by the [[myocardium]]. Intracoronary [[acetylcholine]] can be administered to evaluate endothelium-dependent [[coronary flow reserve]].
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| ===ESC Guidelines for investigation in patients with Syndrome X (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 }} </ref>===
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| {{cquote|
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| ===Class I===
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| '''1.''' [[Chronic stable angina echocardiography|Resting echocardiogram]] in patients with angina and normal or non-obstructed coronary arteries to assess for presence of ventricular hypertrophy and/or [[diastolic dysfunction]]. ''(Level of Evidence: C)''
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| ===Class IIb===
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| '''1.''' Intracoronary acetylcholine during coronary arteriography, if the arteriogram is visually normal, to assess endothelium-dependent coronary flow reserve, and exclude [[vasospasm]]. ''(Level of Evidence: C)''
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| '''2.''' Intracoronary ultrasound, coronary flow reserve, or FFR measurement to exclude missed obstructive lesions, if angiographic appearances are suggestive of a nonobstructive lesion rather than completely normal, and stress imaging techniques identify an extensive area of [[ischaemia]]. ''(Level of Evidence: C)''}}
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| ==Treatment==
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| The mainstay of treatment in patients with Syndrome X are [[calcium channel blocker]]s, such as [[nifedipine]] and [[diltiazem]]. Other therapies include:
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| *[[Nitrates]]. Sublingual nitroglycerine is often not as effective in the patient with Syndrome X as it is in the patient with obstructive epicardial disease, with only 42% of patients reporting relief <ref name="pmid7884081">{{cite journal| author=Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA| title=Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. | journal=J Am Coll Cardiol | year= 1995 | volume= 25 | issue= 4 | pages= 807-14 | pmid=7884081 | doi=10.1016/0735-1097(94)00507-M | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7884081 }} </ref>.
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| *[[Beta blockers]]
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| *[[Aminophylline]] - may be effective via inhibition of adenosine receptors.
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| *[[Estrogen]] - may be effective in women.
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| *[[Ranolazine]] In a recent randomized, controlled trial of ranolzazine in women with Syndrome X, ranolazine was found to be superior to placebo with respect to physical functioning (p = 0.046), angina stability (p = 0.008), and quality of life (p = 0.021). With respect to objective quantitative measure, ranolazine administration tended to be associated with higher (improved) CMR mid-ventricular MPRI (2.4 [2.0 minimum, 2.8 maximum] vs. 2.1 [1.7 minimum, 2.5 maximum], p = 0.074). Women with a coronary flow reserve (CFR) ≤ 3.0 achieved significantly greater improvement in MPRI on ranolazine versus placebo (Δ in MPRI 0.48 vs. -0.82, p = 0.04)<ref name="pmid21565740">{{cite journal| author=Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y et al.| title=Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. | journal=JACC Cardiovasc Imaging | year= 2011 | volume= 4 | issue= 5 | pages= 514-22 | pmid=21565740 | doi=10.1016/j.jcmg.2011.03.007 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21565740 }} </ref>.
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| *[[Estrogen replacement therapy]]: [[ERT]] or selective ERT may reduce the frequency of [[chest pain]] in post menopausal women with Syndrome X <ref name="pmid20935411">{{cite journal| author=Chen YX, Luo NS, Lin YQ, Yuan WL, Xie SL, Nie RQ et al.| title=Selective estrogen receptor modulators promising for cardiac syndrome X. | journal=J Postgrad Med | year= 2010 | volume= 56 | issue= 4 | pages= 328-31 | pmid=20935411 | doi=10.4103/0022-3859.70936 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20935411 }} </ref>.
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| ===ESC Guidelines for pharmacological therapy to improve symptoms in patients with Syndrome X (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 }} </ref>===
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| {{cquote|
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| ===Class I===
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| '''1.''' Therapy with [[nitrates]], [[beta blockers]], and [[calcium channel blockers]] alone or in combination. ''(Level of Evidence: B)''
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| '''2.''' [[Statin]] therapy in patients with [[hyperlipidaemia]]. ''(Level of Evidence: B)''
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| '''3.''' [[ACE inhibitors]] in patients with [[hypertension]]. ''(Level of Evidence: C)''
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| ===Class IIa===
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| '''1.''' Trial of therapy with other anti-anginals including nicorandil and metabolic agents. ''(Level of Evidence: C)''
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| ===Class IIb===
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| '''1.''' [[Aminophylline]] for continued pain, despite Class I measures. ''(Level of Evidence: C)''
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| '''2.''' Imipramine for continued pain, despite Class I measures. ''(Level of Evidence: C)''}}
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
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| ==Review Articles==
| | {{WH}} |
| *[http://heartdisease.about.com/cs/coronarydisease/a/CSX.htm Cardiac Syndrome X]
| | {{WS}} |
| *[http://www.texasheartinstitute.org/HIC/Topics/Cond/CardiacSyndromeX.cfm Texas Heart Institute]
| | [[Category:Disease]] |
| *[http://content.nejm.org/cgi/content/full/347/17/1377 New England Journal of Medicine Editorials]
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| {{Circulatory system pathology}} | |
| {{SIB}} | |
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| [[Category:Ailments of unknown etiology]] | |
| [[Category:Cardiology]] | | [[Category:Cardiology]] |
| [[Category:Disease state]]
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| [[Category:Ischemic heart disease]]
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| [[Category:Mature chapter]]
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