Presentation is loading. Please wait.

Presentation is loading. Please wait.

Variant angina & Microvascular angina

Similar presentations


Presentation on theme: "Variant angina & Microvascular angina"— Presentation transcript:

1 Variant angina & Microvascular angina
Dr Ranjith MP Senior Resident Department of Cardiology Government Medical college Kozhikode

2 Variant angina

3 Introduction Described as "A variant form of angina pectoris" by Dr. Myron Prinzmetal in 1959 Prinzmetal or coronary vasospastic angina Episodes of angina pectoris, usually at rest and often between midnight and early morning, in association with ST-segment elevation on the ECG Episodes are triggered by coronary artery vasospasm in the absence of high grade coronary artery stenosis

4 Population at Risk Associated with other vasospastic disorders like Raynauds, or migraine headaches Patients with cocaine abuse, smoking, insulin resistance, Food-born botulism, Magnesium deficiency Hyperventilation can precipitate Younger patient population (age < 50) More common in women with normal coronaries (pure VA) and in men with organic lesions (non-pure) More frequent in Japan compared to white (Japan: up to 29%,France: 12% US 4%)

5 Pathogenesis Focal spasm of a major coronary artery
Transient myocardial ischemia causes angina any patients. MI may develop in some Vascular smooth muscle hyper-reactivity is thought to be central to the pathogenesis of variant angina Spasm occurs in the absence of any preceding increase in myocardial oxygen demand & in normal or diseased vessels Spasm is usually focal. Spasm in more than one site and diffuse spasm have been described Variant angina is usually caused by focal spasm (of the smooth muscle layer of the arterial wall) of a major coronary artery [2,3], resulting in a high-grade obstruction. Transient myocardial ischemia causes angina in many patients; myocardial infarction may develop in some [1,4]. Vascular smooth muscle hyper-reactivity is thought to be central to the pathogenesis of variant angina [1-3]. Spasm occurs in the absence of any preceding increase in myocardial oxygen demand (eg, exercise) and in normal or diseased vessels. It is usually focal in its anatomic distribution, although spasm in more than one site and diffuse spasm have been described [5]. Spasm can occur in angiographically normal coronary vessels and also at the site of atherosclerotic plaques of different severity.

6 Pathogenesis Vascular smooth muscle hyper-reactivity is a key factor in the pathogenesis of coronary artery spasm Multiple receptors have been involved in this spasm including acetylcholine, serotonin, histamine, noradrenaline, and dopamine Receptor antagonists (eg, ketanserin and prazosin) do not inhibit spasm. Inhibition of smooth muscle contractile mechanisms using other (non-receptor) pathways (eg, nitrates, calcium channel blockers) is effective Increased calcium sensitivity of the vascular myosin light chain mediated by enhanced Rho kinase activity and enhanced phospholipase C activity have been shown to have a role Important observations include

7 Pathogenesis Autonomic nervous system —imbalance of vagal and sympathetic tone in triggering coronary spasm Episodes of variant angina occur more often from midnight to early morning (when vagal tone is higher) Endothelial dysfunction —may be a predisposing factor Associated microvascular dysfunction

8 Clinical presentation
Chronic pattern of recurrent episodes of chest pain Episodes are predominantly at rest and that many occur from midnight to early morning Each episode of chest pain generally lasts 5 to 15 minutes Physical examination- no findings characteristic for VA. However, during an episode, tachycardia, hypertension, diaphoresis, and a gallop rhythm may be present

9 Investigations 12 lead ECG is usually normal between anginal episodes
During an acute episode- ST elevation in multiple leads The ST-segment returns to baseline rapidly upon resolution of symptoms. Occasionally, a transient period of T wave inversion may be seen Other reported ECG abnormalities include a tall and broad R wave, disappearance of the S wave, a taller T wave, and negative U waves Ambulatory ECG monitoring – help in the diagnosis, assess the efficacy of therapy

10 Investigations Role of stress testing Role of coronary arteriography
Angina and no ST-segment elevation should undergo stress testing Most will have a normal noninvasive stress test Exercise-induced spasm with ST-segment elevation- 10 to 30% Stress echocardiography with ergonovine provocation has been used to diagnose variant angina, not recommend now Role of coronary arteriography  In patients with suspected variant angina based on the history and an ECG severe fixed obstruction needs to be excluded Reasonable to refer a patient with a strong history consistent with VA if episodes of pain did not occur during ambulatory monitoring.

11 Investigations Three provocative tests- done only when the diagnosis of VA is suspected, but not firmly established Ergonovine Acetylcholine Associated with a low frequency of serious complications (0.6 %) It is preferred to either ergonovine or hyperventilation, by some Hyperventilation A high specificity (100 percent) & a sensitivity of 55 to 95% A possible Mechanism for hyperventilation induction of coronary vasospasm is from promotion of an intracellular influx of calcium ions, induced by the alkalotic state, which then stimulates the vascular contractile process, leading to coronary vasospasm

12 Differential diagnosis
Fixed obstructive coronary artery disease Early repolarization - generally occurs in patients without classic angina pectoris and in whom the ST-elevation is chronic Acute pericarditis & stress-induced cardiomyopathy - characterized by pain that has been present for hours or days before presentation

13 Differential diagnosis
Pericarditis - sharp pain that is affected by position or breathing & abnormal echocardiography STEMI - pain and ST-elevation are usually present for > 15 minutes Cardiac syndrome X - ST depression on ECG during episodes GERD with esophageal spasm

14 Treatment  Reduces the frequency of symptomatic episodes and appears to decrease the frequency of serious complications Smoking cessation  - significant decrease in the frequency of episodes Sublingual nitroglycerin decrease the duration of symptoms and ischemia

15 Treatment  Nitrates and calcium channel blockers (nifedipine, diltiazem, and verapamil) are effective and both prevent vasoconstriction and promote vasodilation in the coronary vasculature There are no studies comparing one therapy to another In one study the use of a calcium channel blocker therapy was an independent predictor of myocardial infarct-free survival in VA patients Guanethidine and clonidine - not well studied in this setting

16 Treatment  Rho kinase inhibitors – Fasudil, shown to inhibit acetylcholine-induced spasm Statins - Effective in preventing coronary spasm and may exert their benefits via endothelial nitric oxide or direct effects on the vascular smooth muscle Fluvastatin 30 mg daily was evaluated in a trial of 64 patients .After six months ACh-induced coronary artery spasm was significantly lower in fluvastatin group compared to those who did not (48 Vs 79 %) Magnesium – In a study of 22 patients, those administered IV Mg (n = 14) compared with placebo (n = 8) exhibited coronary vasodilation

17 Treatment  Percutaneous coronary intervention - may be helpful if significant obstructive CAD is present and thought to be a potential trigger for focal spasm In a study of 45 patients with documented vasospastic angina and a severe stenosis who underwent balloon only angioplasty or stenting. After a seven-month follow-up, no restenosis was observed and repeat provocative testing with intracoronary acetylcholine did not induce spasm at the site of the initial stenosis; however, spasm at a different site in the dilated vessel and/or in another vessel occurred in 77 percent of patients and multivessel spasm occurred in 62 percent Effective medical therapy, such as calcium channel blockers, should be continued after percutaneous revascularization Concerns about specific drugs — Nonselective beta blockers, such as propranolol can exacerbate vasospasm and should be avoided [74]. In addition, aspirin should be used with caution and at low doses, as it is an inhibitor of prostacyclin production at high doses [75]. However, for patients with atherosclerotic cardiovascular disease, we give aspirin 75 to 81 mg daily.

18 Treatment Concerns about specific drugs
 Nonselective beta blockers, such as propranolol should be avoided Aspirin should be used with caution and at low doses All medications of the triptan class should be avoided 5-Fluorouracil induce coronary artery spasm Concerns about specific drugs — Nonselective beta blockers, such as propranolol can exacerbate vasospasm and should be avoided [74]. In addition, aspirin should be used with caution and at low doses, as it is an inhibitor of prostacyclin production at high doses [75]. However, for patients with atherosclerotic cardiovascular disease, we give aspirin 75 to 81 mg daily.

19 Complications   Myocardial infarction and life-threatening arrhythmias may occur in approximately 25 percent of untreated patients Myocardial infarction - usually due to concurrent obstructive CAD With variant angina alone, coronary vasospasm may trigger thrombus formation Lipoprotein(a) may play a role in this setting. It interferes with fibrinolysis by competing with plasminogen binding to molecules and cells

20 Complications Arrhythmias - may be life-threatening
The type of arrhythmia is determined in part by the vessel & territory involved Heart block - RCA, VT- LAD The optimal approach to patients with variant angina & SCD is unknown. In an observational study of 23 patients with VA in whom an ICD was placed for a documented ventricular arrhythmia, all patients were alive during a median follow-up of 2.1 yrs (4 VF & 1 pulseless electrical activity) Patients with high risk features such as obstructive CAD, large ST elevations, focal proximal epicardial coronary artery spasm, increased vasospastic and arrhythmic activity, and multivessel coronary artery spasm who are on maximal or submaximal doses of Ca channel blockers ICD is a better choice

21 Prognosis Infarct-free survival at 10 - over 80 percent
Independent predictors of infarct-free survival include Extent and severity of CAD SVD has 99 and 94% survival at 1 and 5 year MVD has 87 and 77% survival at 1 and 5 year Use of calcium channel blockers Patients with a positive initial response to CCB are twice as likely to have an event free clinical course compared to those with a poor response initially Arrhythmic complication

22 Summary Variant angina is characterized by spontaneous episodes of angina in association with ST elevation on the ECG. The cause is a transient, abrupt, and marked reduction in the luminal diameter of an epicardial coronary artery due to spasm, leading to transient myocardial ischemia Arrhythmias and MI are potentially life-threatening complications Patients without obstructive CAD have a good long-term prognosis Management includes cessation of smoking and pharmacologic therapy

23 Microvascular angina

24 Introduction First described by Kemp in 1973
It has three characteristic features Angina or angina-like chest pain with exertion ST segment depression on treadmill exercise testing Normal coronary arteriography, with no spontaneous or inducible epicardial coronary artery spasm on ergonovine or acetylcholine provocation

25 Pathogenetic mechanisms
Metabolic abnormalities Impairment of left ventricular function over time Impaired coronary flow reserve Abnormal pain perception Increased tone of microvasculature Endothelial dysfunction Increased sympathetic tone Potassium pump alteration Oestrogen deficiency in post-menopausal women Early coronary artery disease not detectable on angiography

26 Clinical characteristics
More common in women than men Typically younger than those with angina due to CAD (mean age 49±9 Yrs. in two series) Chest pain is similar to angina-like pain in 50% The pain may be precipitated by effort, but also occurs at rest Myocardial ischemia and/or coronary microvascular dysfunction is present in 20 to 50 percent of women with chest pain and normal coronary arteries

27 Clinical characteristics
Duration of anginal-type chest pain is often prolonged. In a review of 99 patients the average duration of chest pain was more than 10 mts in 53 %, and more than 30 minutes in 35%. Many did not respond to S/L nitrates A strong association between cardiac syndrome X and psychiatric disorders such as panic anxiety is observed Rheumatologic disorders, such as fibromyalgia and costochondritis, and noncardiac causes of chest pain, such as esophageal dysfunction, have occasionally been reported in patients with cardiac syndrome X

28 Diagnosis Diagnosis is by exclusion
Should be considered when a patient (often a postmenopausal or perimenopausal woman) describes effort-related anginal pain that lasts 10 minutes or longer after cessation of activity and that responds inconsistently to sublingual nitrates ECG - Transient ST segment depression with anginal pain Exercise testing  - Horizontal or downsloping ST segment depression during exercise, as seen in patients with obstructive CAD

29 Diagnosis    Exercise thallium-201 myocardial scintigraphy - may demonstrate regional myocardial perfusion defects during exercise Some reports have demonstrated neither perfusion defects nor RWMA after dobutamine or transesophageal atrial pacing, despite the frequent provocation of chest pain . It is possible that ischemia is limited to the subendocardium, which could explain the absence of RWMA CMR perfusion imaging - detect regional differences in myocardial blood flow In a study , cardiac syndrome X patients with dobutamine stress induced myocardial perfusion defects in LAD territory on CMR had a lower CFR to adenosine compared to those without perfusion defects in LAD territory. This study is evidence of coronary microcirculation dysfunction in patients with cardiac syndrome X

30 Diagnosis CAG - A normal CAG is a necessary component of the diagnosis
Tissue level perfusion, as determined by myocardial blush grade on CAG, was evaluated in a series of 55 patients and 44 controls . An abnormal blush grade was significantly more common in pts with cardiac syndrome X (58 Vs 20%) IVUS - may detect intramural atheroma Coronary sinus filling time - assess the transit time through coronary microcirculation. A recent study published from our department showed CSFT was significantly delayed in patients with angina and normal coronaries compared to control group (Mean CSFT ± 0.72 s & 3.46 ± 0.99, p = 0.001)

31 Prognosis Cardiac syndrome X with stable angina have a excellent prognosis, while those with ACS have an appreciable acute mortality although lower than that in patients with angiographic coronary disease In CASS registry of over 4000 patients with normal or near normal CAG the 7yr survival rate was 96 % in those with normal CAG & 92% in mild disease Only a minority of patients show evidence of progressive disease on repeat CAG In a series of 138 patients with chest pain and normal CAG at baseline, CAG was repeated in 24 during a 5yr follow-up because of UA. Only 2 patients had progression to significant stenosis Coronary Artery Surgery Study (CASS) registry

32 Risk stratification MRS handgrip stress testing - measurement of myocardial high-energy phosphates after hand-grip exercise. Among women without CAD, abnormal MRS consistent with myocardial ischemia predicted cardiovascular outcome In a study at 3yr follow up, the frequency of cardiovascular events (primarily hospitalization for unstable angina) was 13 percent in the 60 women with no obstructive CHD and normal MRS, 43 percent in the 14 women with no obstructive CHD and an abnormal MRS, and 48 percent in a reference population of 352 women with CHD

33 Risk stratification Stress testing - can detect patients at increased risk In a study of 457 patients, 359 with normal CAG, and the remainder with less than 50% stenosis. Dipyridamole stress echocardiography was abnormal in 43 patients (9 %). At a median follow-up of 7.1 years, these patients had a significantly higher rates of overall mortality (18 Vs 7 %) and cardiac mortality (7.0 Vs 2.7%) compared to those with a normal stress test

34 Treatment    Different therapeutic strategies have been proposed depending upon the prevailing pathogenic mechanism, comorbidity, and clinical presentation Beta blockers -  Most effective in reducing the frequency and severity of angina and in improving exercise tolerance. No definite RCTs available Calcium channel blockers - Not effective or less predictably effective Nitrates -Improvement with sublingual nitrates in about 40 percent of patients

35 Treatment    ACE inhibitors and statins – A RCT in which 45 patients with cardiac syndrome X were assigned to treatment with either ramipril (10 mg OD) plus atorvastatin (40 mg OD) or placebo . After six months, patients treated with atorvastatin and ramipril had significant improvements in brachial artery flow-mediated vasodilation (a marker of endothelial function), exercise duration, and angina frequency compared to placebo Imipramine - Low dose imipramine, may be effective in some patient The mechanism of benefit of such therapy is not certain but may be a consequence of reduction in oxidative stress. During the study, measurements of superoxide dismutase (SOD) activity were made before and after six months of treatment [60]. Baseline SOD levels were elevated compared to healthy control subjects, suggesting an induced increase enzyme activity to counter elevated superoxide anion formation. After treatment with ramipril and atorvastatin, but not placebo, SOD levels were significantly reduced. (See "Endothelial dysfunction", section on 'Pathophysiology'.)

36 Treatment    Hormone therapy - May be beneficial in postmenopausal women. In a double-blind controlled trial of 25 such women, hormone therapy significantly reduced the frequency of anginal episodes (3.7 versus 7.3 episodes per 10 days with placebo) . Estrogen may act by improving endothelium-dependent coronary vasomotion The Women's Health Initiative, mostly of primary prevention, and the HERS trials of secondary prevention showed that estrogen-progestin replacement had no cardioprotective effect and may have produced harm, increasing the risk of coronary disease, stroke, venous thromboembolism, and breast cancer The mechanism of benefit of such therapy is not certain but may be a consequence of reduction in oxidative stress. During the study, measurements of superoxide dismutase (SOD) activity were made before and after six months of treatment [60]. Baseline SOD levels were elevated compared to healthy control subjects, suggesting an induced increase enzyme activity to counter elevated superoxide anion formation. After treatment with ramipril and atorvastatin, but not placebo, SOD levels were significantly reduced. (See "Endothelial dysfunction", section on 'Pathophysiology'.)

37 Treatment      Physical training  - compared to no intervention, exercise training improved exercise capacity by 34 % & delayed onset of pain during exercise by 100 % Alpha blockers - studies have shown no effect on exercise-induced angina Aminophylline - adenosine receptor antagonist. In a trial of oral aminophylline, the time to the development of chest pain on exercise testing was prolonged & the number of chest pain episodes over a 3wk interval were reduced, but the development of ST segment depression was not diminished Spinal cord stimulation - successful in the treatment of refractory angina due to coronary heart disease Alpha blockers — The prevention of coronary microvascular constriction by an alpha-adrenergic blocker is theoretically attractive. However, most studies have shown no effect on exercise-induced angina [66,67] and alpha-1 blockade does not affect myocardial blood flow at rest or after dipyridamole or the development of chest pain and ischemic ECG changes after dipyridamole [68].

38 Summary    Cardiac syndrome X is defined as angina-like chest pain with exertion, positive ECG response (ST segment depression) on treadmill exercise testing and normal CAG with no spontaneous or inducible epicardial coronary artery spasm on ergonovine or acetylcholine provocation Incidence is more common in women  Most patients with cardiac syndrome X and stable symptoms have an excellent prognosis Therapy is tailored to individual patient. Reassurance is key Beta blockers seem to be effective in decreasing frequency and severity of symptoms Sublingual nitroglycerin may also help symptoms in some patients but calcium channel blockers are not very effective

39 Thank you

40 MCQ -1 False statement about variant angina?
ECG shows transient ST elevation Patient may have obstructive CAD Usually preceded by heavy excursion Usually occurs in early night and early morning

41 MCQ - 2 Population at risk for variant angina include all except
Patients with cocaine abuse & smoking Insulin resistance Food-born botulism Calcium deficiency

42 MCQ - 3 Provocative tests not used in diagnosis of variant angina
Ergonovine Acetylcholine Hyperthermia Hyperventilation

43 MCQ - 4 Statin trial in variant angina is with ……………………… Rosuvatatin
Fluvastatin Simvastatin Prasuvastatin

44 MCQ - 5 False statement about variant angina
Infarct-free survival at 10 is over 80 percent Independent predictors of infarct-free survival include extent and severity of CAD Trials have shown nitrates are better than calcium channel blockers in preventing recurrence of chest pain Use of calcium channel blockers is an independent predictors of infarct-free survival

45 MCQ - 6     Characteristic features of microvascular angina include all except Angina or angina-like chest pain with exertion ST segment elevation on treadmill exercise testing Normal coronary arteriography No spontaneous or inducible epicardial coronary artery spasm on ergonovine or acetylcholine provocation

46 MCQ - 7 False statement about microvascular angina is
More common in women than men Typically younger than those with angina due to CAD Chest pain is similar to angina-like pain in >70% of cases The pain may be precipitated by effort

47 MCQ - 8 False statement about microvascular angina is
Myocardial ischemia and/or coronary microvascular dysfunction is present in >70% of cases Duration of anginal-type chest pain may be more than 30 minutes A strong association between psychiatric disorders such as panic anxiety Exercise testing  shows horizontal or downsloping ST segment depression

48 MCQ - 9 False statement about treatment of variant angina
Beta blockers are effective in reducing the frequency and severity of angina Calcium channel blockers are equally effective as Beta blockers Improvement with sublingual nitrates in about 40 percent of patients Alpha blockers - studies have shown no effect on exercise-induced angina

49 MCQ - 10    All the following treatment modalities have good benefit risk ratio in microvascular angina except ACE inhibitors Imipramine Hormone therapy Statins

50 MCQ -1 False statement about variant angina?
ECG shows transient ST elevation Patient may have obstructive CAD Usually preceded by heavy excursion Usually occurs in early night and early morning

51 MCQ - 2 Population at risk for variant angina include all except
Patients with cocaine abuse & smoking Insulin resistance Food-born botulism Calcium deficiency

52 MCQ - 3 Provocative tests not used in diagnosis of variant angina
Ergonovine Acetylcholine Hyperthermia Hyperventilation

53 MCQ - 4 Statin trial in variant angina is with ……………………… Rosuvatatin
Fluvastatin Simvastatin Prasuvastatin

54 MCQ - 5 False statement about variant angina
Infarct-free survival at 10 is over 80 percent Independent predictors of infarct-free survival include extent and severity of CAD Trials have shown nitrates are better than calcium channel blockers in preventing recurrence of chest pain Use of calcium channel blockers is an independent predictors of infarct-free survival

55 MCQ - 6     Characteristic features of microvascular angina include all except Angina or angina-like chest pain with exertion ST segment elevation on treadmill exercise testing Normal coronary arteriography No spontaneous or inducible epicardial coronary artery spasm on ergonovine or acetylcholine provocation

56 MCQ - 7 False statement about microvascular angina is
More common in women than men Typically younger than those with angina due to CAD Chest pain is similar to angina-like pain in >70% of cases The pain may be precipitated by effort

57 MCQ - 8 False statement about microvascular angina is
Myocardial ischemia and/or coronary microvascular dysfunction is present in >70% of cases Duration of anginal-type chest pain may be more than 30 minutes A strong association between psychiatric disorders such as panic anxiety Exercise testing  shows horizontal or downsloping ST segment depression

58 MCQ - 9 False statement about treatment of variant angina
Beta blockers are effective in reducing the frequency and severity of angina Calcium channel blockers are equally effective as Beta blockers Improvement with sublingual nitrates in about 40 percent of patients Alpha blockers - studies have shown no effect on exercise-induced angina

59 MCQ - 10    All the following treatment modalities have good benefit risk ratio in microvascular angina except ACE inhibitors Imipramine Hormone therapy Statins


Download ppt "Variant angina & Microvascular angina"

Similar presentations


Ads by Google