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Clinical Case One. Patient:JM: male, 50 years oldOccupation: postman. clinical case one. Presenting complaint:Last 6 months
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1. Atherothrombosis Management in Practice: Clinical Cases This slide kit is the first of four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice. This slide kit is the first of four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice.
2. Clinical Case One Patient:
JM: male, 50 years old
Occupation: postman
3. Diagnosis What is your diagnosis?
Answer
The correct answer is 4. Intermittent claudication.
This is because the typical pain at exercise is relieved by rest.
Arthritis of the hip causes pain, but the pain is relieved by lying down or sitting.
Peripheral neuropathy gives permanent pain, and at least unstable and unsure walking.
Venous disease is the opposite of intermittent claudication – the pain is relieved during exercise.
Finally, sciatic pain produces more of a shooting pain.
Answer
The correct answer is 4. Intermittent claudication.
This is because the typical pain at exercise is relieved by rest.
Arthritis of the hip causes pain, but the pain is relieved by lying down or sitting.
Peripheral neuropathy gives permanent pain, and at least unstable and unsure walking.
Venous disease is the opposite of intermittent claudication – the pain is relieved during exercise.
Finally, sciatic pain produces more of a shooting pain.
4. Physical Examination (I) On presentation:
General status: excellent
Heart and lungs: no abnormalities
BP: 138/88 mmHg
Pulse: regular 88/min
5. Electrocardiogram (ECG) Analysis
The electrocardiogram shows regular sinus rhythm.
When evaluating the QRS complex, one can see clear Q-waves in derivation II, III, and aVF.
These Q-waves are showing an old inferior infarction.
The repolarization is atypical. One can see, in different derivations, flat T-waves with the ST segment just < 1 mm under the zero line. Such ST is called, T-abnormalities.
They are non-specific, but the Q-waves in the derivation II, III, and aVF are typical of an old inferior infarction.
Analysis
The electrocardiogram shows regular sinus rhythm.
When evaluating the QRS complex, one can see clear Q-waves in derivation II, III, and aVF.
These Q-waves are showing an old inferior infarction.
The repolarization is atypical. One can see, in different derivations, flat T-waves with the ST segment just < 1 mm under the zero line. Such ST is called, T-abnormalities.
They are non-specific, but the Q-waves in the derivation II, III, and aVF are typical of an old inferior infarction.
6. Physical Examination (II) Right limb:
Bruit over right femoral artery
Artery pulsations present, including in foot arteries
Left limb:
Bruit over left femoral artery
Femoral artery pulsations present in groin
No pulsations in popliteal or distal pulses
7. Investigation (I) What is your next step in light of JM’s condition?
Answer
There clearly is a problem with JM – the ECG is abnormal and the vascular findings are clearly clinically abnormal.
So just reassuring JM would not be the right thing to do.
JM needs to be examined to determine the magnitude of the problem.
Thus, the examination should be non-invasive, and the best way to approach this is answer 2. Measure ankle pressure.
There is, at this time, no place for duplex scanning, as it describes the anatomy present.
It is much too early to perform contrast arteriography. This should only be carried out when an invasive treatment is one of the possibilities (and this is not yet the case).
Answer
There clearly is a problem with JM – the ECG is abnormal and the vascular findings are clearly clinically abnormal.
So just reassuring JM would not be the right thing to do.
JM needs to be examined to determine the magnitude of the problem.
Thus, the examination should be non-invasive, and the best way to approach this is answer 2. Measure ankle pressure.
There is, at this time, no place for duplex scanning, as it describes the anatomy present.
It is much too early to perform contrast arteriography. This should only be carried out when an invasive treatment is one of the possibilities (and this is not yet the case).
8. Pressure gradients:
Left ankle 80/138 (index = 0.58)
Right ankle 104/138 (index = 0.75)
Investigation (II) Answer
The ankle pressures and the gradients measured are clearly abnormal, so something should be done for JM.
Normally the pressure gradient, which is ankle/arm, is 1 or more with the lowest value at 0.9. Here it is down to 0.58, thus is clearly abnormal.
Treatment is necessary in such a patient and the suggested answer is 4. Drugs and training:
exercise training is to improve the claudication
drugs can eventually help with the claudication, but primarily to reduce atherothrombotic ischemic events such as myocardial infarction and stroke.
Note, interventional treatment, such as percutaneous transluminal angioplasty (PTA) or vascular surgery (answer 5.), is not yet necessary.
Answer
The ankle pressures and the gradients measured are clearly abnormal, so something should be done for JM.
Normally the pressure gradient, which is ankle/arm, is 1 or more with the lowest value at 0.9. Here it is down to 0.58, thus is clearly abnormal.
Treatment is necessary in such a patient and the suggested answer is 4. Drugs and training:
exercise training is to improve the claudication
drugs can eventually help with the claudication, but primarily to reduce atherothrombotic ischemic events such as myocardial infarction and stroke.
Note, interventional treatment, such as percutaneous transluminal angioplasty (PTA) or vascular surgery (answer 5.), is not yet necessary.
9. Treatment (I) Which medication would you consider?
Answer
The correct answer is 7. A combination of drugs.
The antiplatelet drugs should be used to improve the prognosis of JM, but additionally, we should also add drugs that can improve the symptoms (i.e. intermittent claudication).
For the intermittent claudication, one of the possibilities is cilostazol. Another possibility is one of pentoxifylline, buflomedil, or naftidrofuryl. Cilostazol is not on the market in most European countries. For these countries, naftidrofuryl has demonstrated the most promise.
Of the drugs that improve the patient’s prognosis, by reducing ischemic events through platelet inhibition, ASA is the most widely used. Ticlopidine, while offering improved efficacy relative to ASA, has significant safety problems. On the other hand, clopidogrel offers an equivalent improvement in efficacy, without the safety and tolerability issues associated with ticlopidine.
Answer
The correct answer is 7. A combination of drugs.
The antiplatelet drugs should be used to improve the prognosis of JM, but additionally, we should also add drugs that can improve the symptoms (i.e. intermittent claudication).
For the intermittent claudication, one of the possibilities is cilostazol. Another possibility is one of pentoxifylline, buflomedil, or naftidrofuryl. Cilostazol is not on the market in most European countries. For these countries, naftidrofuryl has demonstrated the most promise.
Of the drugs that improve the patient’s prognosis, by reducing ischemic events through platelet inhibition, ASA is the most widely used. Ticlopidine, while offering improved efficacy relative to ASA, has significant safety problems. On the other hand, clopidogrel offers an equivalent improvement in efficacy, without the safety and tolerability issues associated with ticlopidine.
10. Follow-up (I) On discharge:
Training program and low-dose ASA (100 mg o.d.)
11. Investigation (III) How would you approach the TIA problem?
Answer
There clearly is a serious problem with JM – a transient ischemic attack (TIA) is always a warning symptom that should be explored. Therefore, JM’s condition needs to be investigated.
By definition it should be done by non-invasive means. For this, duplex scanning is the best choice.
Most neurologists, at present, ask that in such a situation, on top of the duplex scanning for the carotid arteries in the neck, one adds brain CT scans to examine the intracerebral circulation. So the correct answer is 5. Duplex and brain CT scans.
Answer
There clearly is a serious problem with JM – a transient ischemic attack (TIA) is always a warning symptom that should be explored. Therefore, JM’s condition needs to be investigated.
By definition it should be done by non-invasive means. For this, duplex scanning is the best choice.
Most neurologists, at present, ask that in such a situation, on top of the duplex scanning for the carotid arteries in the neck, one adds brain CT scans to examine the intracerebral circulation. So the correct answer is 5. Duplex and brain CT scans.
12. Imaging Results (I) Analysis
On the right internal carotid artery, there clearly is stenosis.
The duplex scan reveals 50% stenosis of the right internal carotid artery.
Analysis
On the right internal carotid artery, there clearly is stenosis.
The duplex scan reveals 50% stenosis of the right internal carotid artery.
13. Imaging Results (II) Analysis
The duplex scan clearly shows irregularities of the wall all over the left carotid artery.
Such irregularities are interpreted as plaques caused by atherosclerosis of the vascular wall.
Analysis
The duplex scan clearly shows irregularities of the wall all over the left carotid artery.
Such irregularities are interpreted as plaques caused by atherosclerosis of the vascular wall.
14. Imaging Results (III) Analysis
Considering the morphologic picture of the stenosis in the right carotid, together with the velocity patterns that we can evaluate by duplex scanning, we estimate that the degree of stenosis is approximately 50%.
Analysis
Considering the morphologic picture of the stenosis in the right carotid, together with the velocity patterns that we can evaluate by duplex scanning, we estimate that the degree of stenosis is approximately 50%.
15. Treatment (II) How would you treat the TIA? Answer
The degree of stenosis, as seen by the duplex scan, is quite a determining parameter.
JM has a stenosis <70%, so, by definition, we would not approach and treat his TIA by invasive means.
The TIA should be treated with antiplatelet drugs and followed to see how it evolves.
ASA is one of the regular drug choices. Clopidogrel or ticlopidine offer additional efficacy above ASA, although as previously discussed, clopidogrel has a better safety profile, so it could be a good solution to this problem.
JM needs routine follow-ups, because TIA is a warning symptom.
Therefore, 4. Replace ASA with clopidogrel, is considered to be the best answer.*Answer
The degree of stenosis, as seen by the duplex scan, is quite a determining parameter.
JM has a stenosis <70%, so, by definition, we would not approach and treat his TIA by invasive means.
The TIA should be treated with antiplatelet drugs and followed to see how it evolves.
ASA is one of the regular drug choices. Clopidogrel or ticlopidine offer additional efficacy above ASA, although as previously discussed, clopidogrel has a better safety profile, so it could be a good solution to this problem.
JM needs routine follow-ups, because TIA is a warning symptom.
Therefore, 4. Replace ASA with clopidogrel, is considered to be the best answer.*
16. Follow-up (II) 1 year later:
JM is doing fine
Minor claudication remains
No neurologic symptoms
Clopidogrel 75 mg o.d. Discussion
JM is quite a typical patient who has an elevated risk profile in general.
Physicians quite often forget that a patient carrying intermittent claudication is also a patient carrying an increased risk of coronary artery disease and carotid artery disease.
JM is a typical example, presenting with symptoms of intermittent claudication that are soon complicated by carotid artery disease and in this case TIA.
One should remember JM also has coronary artery disease – again, a typical example of multiarterial disease seen so often in this type of patient. Discussion
JM is quite a typical patient who has an elevated risk profile in general.
Physicians quite often forget that a patient carrying intermittent claudication is also a patient carrying an increased risk of coronary artery disease and carotid artery disease.
JM is a typical example, presenting with symptoms of intermittent claudication that are soon complicated by carotid artery disease and in this case TIA.
One should remember JM also has coronary artery disease – again, a typical example of multiarterial disease seen so often in this type of patient.
17. Atherothrombosis Management in Practice – Clinical Cases Clinical Case Two This slide kit contains four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice. This slide kit contains four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice.
18. Clinical Case Two Patient:
KK: male, 58 years old
Presenting complaint:
“My right calf cramps whenever I walk a quarter of a mile uphill”
Symptom present: 2 months
19. Background
20. Physical Examination (I) On presentation:
Height: 5’ 8" (1.72 m)
Weight: 186 lb (84.4 kg)
BP: 164/100 mmHg
Pulse: 84 bpm
Left carotid bruit
21. Physical Examination (II) On presentation:
Lungs: clear to palpation and auscultation
Heart: S4, no murmurs
Abdomen: right lower quadrant bruit, no masses
Extremities:
diminished right femoral pulse
absent right popliteal and pedal pulses
normal left femoral, popliteal, and pedal pulses
22. Investigation (I)
23. Investigation (II)
24. Diagnosis Analysis
KK is a typical patient with systemic atherothrombosis.
There are multiple clinical manifestations of this problem. Foremost, he has peripheral arterial disease (PAD). This is manifested in his history by symptoms of classic intermittent claudication – his calf cramps when he walks a hill – and the physical examination reveals abnormal pulses.
In addition, the patient had a prior MI, indicative of coronary artery disease.
He also has extra-cranial cerebrovascular disease – a carotid bruit was auscultated on physical examination.
This patient has high BP, Type II diabetes mellitus, and also hypercholesterolemia.
As is often the case in patients with atherothrombosis, there is more than one risk factor.
In summary, KK has systemic atherothrombosis. He has multiple clinical manifestations of this problem and multiple risk factors, including:
PAD
coronary artery disease (prior MI)
carotid bruit (asymptomatic)
hypertension
Type II diabetes mellitus
hypercholesterolemia.Analysis
KK is a typical patient with systemic atherothrombosis.
There are multiple clinical manifestations of this problem. Foremost, he has peripheral arterial disease (PAD). This is manifested in his history by symptoms of classic intermittent claudication – his calf cramps when he walks a hill – and the physical examination reveals abnormal pulses.
In addition, the patient had a prior MI, indicative of coronary artery disease.
He also has extra-cranial cerebrovascular disease – a carotid bruit was auscultated on physical examination.
This patient has high BP, Type II diabetes mellitus, and also hypercholesterolemia.
As is often the case in patients with atherothrombosis, there is more than one risk factor.
In summary, KK has systemic atherothrombosis. He has multiple clinical manifestations of this problem and multiple risk factors, including:
PAD
coronary artery disease (prior MI)
carotid bruit (asymptomatic)
hypertension
Type II diabetes mellitus
hypercholesterolemia.
25. Investigation (III) Which one of the following tests should be considered to further evaluate PAD? Answer
The best answer here is 2. Segmental pressure measurements. This non-invasive test enables the examiner to determine the presence of peripheral arterial stenoses, assess their severity, and gain insight into their location.
Pulse-volume recordings are often used as an adjunctive test with segmental pressure measurements. An abnormal pulse-volume recording distal to the stenosis provides further evidence of PAD.
Many laboratories use duplex ultrasonography of the leg to assess PAD, however, it requires considerable time to perform this procedure and the information gained does not necessarily increase the knowledge of the presence or severity of PAD.
Magnetic resonance arteriography (MRA) is a test that can be used to demonstrate the anatomy of the peripheral vasculature. The technology is improving, as is its resolution. However, at this time MRA is not indicated for the routine evaluation of PAD, but may be employed in patients who will ultimately be considered for revascularization procedures.
Contrast arteriography is rarely if ever necessary for diagnostic purposes. It is performed, however, when interventions such as PTA or reconstructive surgery are being considered.Answer
The best answer here is 2. Segmental pressure measurements. This non-invasive test enables the examiner to determine the presence of peripheral arterial stenoses, assess their severity, and gain insight into their location.
Pulse-volume recordings are often used as an adjunctive test with segmental pressure measurements. An abnormal pulse-volume recording distal to the stenosis provides further evidence of PAD.
Many laboratories use duplex ultrasonography of the leg to assess PAD, however, it requires considerable time to perform this procedure and the information gained does not necessarily increase the knowledge of the presence or severity of PAD.
Magnetic resonance arteriography (MRA) is a test that can be used to demonstrate the anatomy of the peripheral vasculature. The technology is improving, as is its resolution. However, at this time MRA is not indicated for the routine evaluation of PAD, but may be employed in patients who will ultimately be considered for revascularization procedures.
Contrast arteriography is rarely if ever necessary for diagnostic purposes. It is performed, however, when interventions such as PTA or reconstructive surgery are being considered.
26. Investigation (IV) Analysis
In this patient, leg segmental pressure measurements were performed.
Normally, the leg pressure and arm pressure are the same. However, in KK the pressure obtained at the right upper thigh is 20 mmHg less than that of the arm. This implies that there is a stenosis proximal to the upper thigh that is causing a pressure gradient and is responsible for the decrease in systolic pressure.
As one goes down the right leg, the pressure obtained at the calf is 110 mmHg. This is a further pressure gradient beyond that observed at the thigh. This would imply an intervening stenosis.
Finally, when pressure measurements were obtained at the right ankle, there is an additional fall in pressure now down to 88 mmHg, implying additional peripheral stenoses affecting the tibial or perineal arteries. The ratio of the right ankle pressure to the arm pressure, or the ABI is 0.51.
One can contrast these findings with the left leg in this patient, which is entirely normal. The systolic pressure measurement obtained at the left upper thigh, lower thigh, calf, and ankle, are the same as, or even slightly greater than, that obtained in the arm. Thus, the ABI is 1.0. This would indicate no evidence of peripheral arterial stenoses.Analysis
In this patient, leg segmental pressure measurements were performed.
Normally, the leg pressure and arm pressure are the same. However, in KK the pressure obtained at the right upper thigh is 20 mmHg less than that of the arm. This implies that there is a stenosis proximal to the upper thigh that is causing a pressure gradient and is responsible for the decrease in systolic pressure.
As one goes down the right leg, the pressure obtained at the calf is 110 mmHg. This is a further pressure gradient beyond that observed at the thigh. This would imply an intervening stenosis.
Finally, when pressure measurements were obtained at the right ankle, there is an additional fall in pressure now down to 88 mmHg, implying additional peripheral stenoses affecting the tibial or perineal arteries. The ratio of the right ankle pressure to the arm pressure, or the ABI is 0.51.
One can contrast these findings with the left leg in this patient, which is entirely normal. The systolic pressure measurement obtained at the left upper thigh, lower thigh, calf, and ankle, are the same as, or even slightly greater than, that obtained in the arm. Thus, the ABI is 1.0. This would indicate no evidence of peripheral arterial stenoses.
27. Investigation (V) Which test is NOT indicated at this time? Answer
KK has evidence of systemic atherothrombosis, and although he presented with symptoms specific to his leg (right calf claudication) the examiner was able to determine that there were other manifestations of atherothrombosis, including coronary artery disease (CAD) and carotid artery disease. It is appropriate to determine the severity of these problems further, in order to develop appropriate treatment strategies.
To further assess the presence of CAD, a provocative test is indicated. A treadmill exercise test is typically performed in patients in whom the diagnosis of CAD is being considered. A treadmill test can be performed in KK, particularly to assess the claudication. However, because of KK’s limited exercise capacity, this test may not be sensitive enough to detect underlying CAD.
Other provocative tests can be considered, those that include nuclear imaging or echocardiography (ECHO). Examples are dipyridamole–sestamibi, dipyridamole–thallium studies, dobutamine–thallium studies or dobutamine ECHO. Any of these studies can be considered to determine whether or not the patient has more CAD than is elicited by history or physical examination.
The answer here is 3. Cardiac catheterization. However, if any provocative tests would suggest the presence of left main artery disease or even three-vessel CAD in the presence of left ventricle (LV) dysfunction, a catheterization might be considered in order to determine whether these possible underlying coronary findings are present, to develop a treatment strategy that could involve intervention.
Carotid ultrasonography is indicated in KK. A left carotid bruit was detected on physical examination. Even though KK has no symptoms of cerebrovascular ischemia, a critical stenosis would be considered by some as an indication for carotid endarterectomy.
An abdominal ultrasound examination is a reasonable test for this individual. He has hypertension as well as a right lower quadrant bruit. Therefore, there is a possibility that he has underlying renal artery stenosis. One of the tests that can be considered is duplex ultrasonography of the renal arteries to look for the presence of renal artery stenosis. The abdominal ultrasound examination will also enable the examiner to assess kidney size.
Answer
KK has evidence of systemic atherothrombosis, and although he presented with symptoms specific to his leg (right calf claudication) the examiner was able to determine that there were other manifestations of atherothrombosis, including coronary artery disease (CAD) and carotid artery disease. It is appropriate to determine the severity of these problems further, in order to develop appropriate treatment strategies.
To further assess the presence of CAD, a provocative test is indicated. A treadmill exercise test is typically performed in patients in whom the diagnosis of CAD is being considered. A treadmill test can be performed in KK, particularly to assess the claudication. However, because of KK’s limited exercise capacity, this test may not be sensitive enough to detect underlying CAD.
Other provocative tests can be considered, those that include nuclear imaging or echocardiography (ECHO). Examples are dipyridamole–sestamibi, dipyridamole–thallium studies, dobutamine–thallium studies or dobutamine ECHO. Any of these studies can be considered to determine whether or not the patient has more CAD than is elicited by history or physical examination.
The answer here is 3. Cardiac catheterization. However, if any provocative tests would suggest the presence of left main artery disease or even three-vessel CAD in the presence of left ventricle (LV) dysfunction, a catheterization might be considered in order to determine whether these possible underlying coronary findings are present, to develop a treatment strategy that could involve intervention.
Carotid ultrasonography is indicated in KK. A left carotid bruit was detected on physical examination. Even though KK has no symptoms of cerebrovascular ischemia, a critical stenosis would be considered by some as an indication for carotid endarterectomy.
An abdominal ultrasound examination is a reasonable test for this individual. He has hypertension as well as a right lower quadrant bruit. Therefore, there is a possibility that he has underlying renal artery stenosis. One of the tests that can be considered is duplex ultrasonography of the renal arteries to look for the presence of renal artery stenosis. The abdominal ultrasound examination will also enable the examiner to assess kidney size.
28. Treatment (I) What treatment should be initiated to reduce potential cardiovascular events? Answer
There are two major themes of intervention that should be considered in patients with PAD or other manifestations of atherothrombosis (or even in those with other manifestations of atherothrombosis) to reduce adverse cardiovascular events. The first is risk factor modifications and the second is antiplatelet therapy.
KK has multiple risk factors for atherothrombosis, including hypertension, diabetes mellitus, cigarette smoking, and hypercholesteremia.
Interventions that focus on smoking cessation, optimal blood glucose control, lowering of high cholesterol, and reduction of high BP will all realize favorable effects in terms of reducing adverse cardiovascular events, including MI, stroke, and vascular death.
In addition to risk factor modification, antiplatelet therapy is an extremely important intervention that should be initiated in all of these patients. The Antiplatelet Trialists’ Collaboration1 have found that antiplatelet therapy reduces adverse cardiovascular events in patients with atherothrombosis.
Recently there has been a trial comparing ASA to a thienopyridine derivative, clopidogrel. In the CAPRIE trial,2 clopidogrel was more effective than ASA in reducing adverse cardiovascular events in patients with a variety of manifestations of atherosclerosis, including acute MI, recent ischemic stroke, and PAD. Among the patients with PAD, clopidogrel was particularly effective compared to ASA in reducing the risk of MI, stroke, or vascular death.Answer
There are two major themes of intervention that should be considered in patients with PAD or other manifestations of atherothrombosis (or even in those with other manifestations of atherothrombosis) to reduce adverse cardiovascular events. The first is risk factor modifications and the second is antiplatelet therapy.
KK has multiple risk factors for atherothrombosis, including hypertension, diabetes mellitus, cigarette smoking, and hypercholesteremia.
Interventions that focus on smoking cessation, optimal blood glucose control, lowering of high cholesterol, and reduction of high BP will all realize favorable effects in terms of reducing adverse cardiovascular events, including MI, stroke, and vascular death.
In addition to risk factor modification, antiplatelet therapy is an extremely important intervention that should be initiated in all of these patients. The Antiplatelet Trialists’ Collaboration1 have found that antiplatelet therapy reduces adverse cardiovascular events in patients with atherothrombosis.
Recently there has been a trial comparing ASA to a thienopyridine derivative, clopidogrel. In the CAPRIE trial,2 clopidogrel was more effective than ASA in reducing adverse cardiovascular events in patients with a variety of manifestations of atherosclerosis, including acute MI, recent ischemic stroke, and PAD. Among the patients with PAD, clopidogrel was particularly effective compared to ASA in reducing the risk of MI, stroke, or vascular death.
29. Treatment (II) What is the most effective initial strategy to relieve symptoms of claudication? Answer
KK presented to the physician for treatment of a symptom of right calf cramping when walking. Although it is important for the physician to address the presence of atherothrombosis to reduce adverse cardiovascular events, it is important for the patient to feel better.
Perhaps one of the most effective ways of improving symptoms of claudication is an exercise rehabilitation program – it has been demonstrated that supervised exercise rehabilitation, consisting of 30 min sessions of treadmill walking at least three times a week and lasting for at least 3 months, results in at least a 100% improvement in the distance walked before a patient develops claudication. Answer 1. Exercise rehabilitation should be considered in all patients who present with symptoms of claudication.
Following institution of an exercise rehabilitation program, pharmacotherapy may be considered in selected patients. Available drugs approved by the FDA include pentoxifylline and cilostazol. Meta-analyses of studies that have examined the efficacy of pentoxifylline have shown only limited benefit. Cilostazol has been associated with an improvement in walking distance of approximately 50–60% over that achieved by placebo in controlled trials.
Other strategies such as PTA or vascular surgery are usually reserved for those patients with severe disabling claudication or with rest pain secondary to critical limb ischemia. For KK, it is more appropriate to use an exercise program and selected use of pharmacotherapy to improve the symptoms of claudication. If this patient develops progressive symptoms of claudication to the point of disability, then other strategies such as PTA or vascular surgery could be considered at that time.
Answer
KK presented to the physician for treatment of a symptom of right calf cramping when walking. Although it is important for the physician to address the presence of atherothrombosis to reduce adverse cardiovascular events, it is important for the patient to feel better.
Perhaps one of the most effective ways of improving symptoms of claudication is an exercise rehabilitation program – it has been demonstrated that supervised exercise rehabilitation, consisting of 30 min sessions of treadmill walking at least three times a week and lasting for at least 3 months, results in at least a 100% improvement in the distance walked before a patient develops claudication. Answer 1. Exercise rehabilitation should be considered in all patients who present with symptoms of claudication.
Following institution of an exercise rehabilitation program, pharmacotherapy may be considered in selected patients. Available drugs approved by the FDA include pentoxifylline and cilostazol. Meta-analyses of studies that have examined the efficacy of pentoxifylline have shown only limited benefit. Cilostazol has been associated with an improvement in walking distance of approximately 50–60% over that achieved by placebo in controlled trials.
Other strategies such as PTA or vascular surgery are usually reserved for those patients with severe disabling claudication or with rest pain secondary to critical limb ischemia. For KK, it is more appropriate to use an exercise program and selected use of pharmacotherapy to improve the symptoms of claudication. If this patient develops progressive symptoms of claudication to the point of disability, then other strategies such as PTA or vascular surgery could be considered at that time.
30. Treatment (III) Treatment strategy: Discussion
The treatment strategies employed for KK were designed first to reduce the risk of adverse cardiovascular events and second to improve his symptoms of claudication.
In order to reduce adverse cardiovascular events, risk factor management was intensified:
diabetes mellitus: treatment was optimized to lower KK’s blood glucose, in order that HbA1C fell to less than 7%
hypercholesterolemia (identified during laboratory work) was treated with the initiation of the statin, HMG-CoA reductase inhibitor
hypertension was further evaluated by a duplex renal ultrasound as well as a magnetic resonance angiogram of the renal arteries. These demonstrated no evidence of renal artery stenosis. Therefore, KK’s hypertension was managed further with pharmacotherapy
KK enrolled in a smoking-cessation program and has discontinued the use of cigarettes.
antiplatelet regimen, clopidogrel 75 mg o.d., was started to further reduce the risk of adverse cardiovascular events
exercise rehabilitation program was drawn up to address claudication.Discussion
The treatment strategies employed for KK were designed first to reduce the risk of adverse cardiovascular events and second to improve his symptoms of claudication.
In order to reduce adverse cardiovascular events, risk factor management was intensified:
diabetes mellitus: treatment was optimized to lower KK’s blood glucose, in order that HbA1C fell to less than 7%
hypercholesterolemia (identified during laboratory work) was treated with the initiation of the statin, HMG-CoA reductase inhibitor
hypertension was further evaluated by a duplex renal ultrasound as well as a magnetic resonance angiogram of the renal arteries. These demonstrated no evidence of renal artery stenosis. Therefore, KK’s hypertension was managed further with pharmacotherapy
KK enrolled in a smoking-cessation program and has discontinued the use of cigarettes.
antiplatelet regimen, clopidogrel 75 mg o.d., was started to further reduce the risk of adverse cardiovascular events
exercise rehabilitation program was drawn up to address claudication.
31. Follow-up Discussion
After 3 months KK found that he was able to walk a distance of half a mile uphill before his symptoms occurred. His exercise programme was considered successful.
This case is an excellent example of a patient with systemic atherothrombosis and multiple risk factors.
Although KK presented with a symptom that was of concern to him, the physician had the opportunity to identify the presence of systemic atherothrombosis and initiate measures that will not only favorably affect the symptom that concerns the patient, but also reduce the risk of adverse cardiovascular events that might cause future disability or even death.
Discussion
After 3 months KK found that he was able to walk a distance of half a mile uphill before his symptoms occurred. His exercise programme was considered successful.
This case is an excellent example of a patient with systemic atherothrombosis and multiple risk factors.
Although KK presented with a symptom that was of concern to him, the physician had the opportunity to identify the presence of systemic atherothrombosis and initiate measures that will not only favorably affect the symptom that concerns the patient, but also reduce the risk of adverse cardiovascular events that might cause future disability or even death.
32. Atherothrombosis Management in Practice – Clinical Cases Clinical Case Three This slide kit contains four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice. This slide kit contains four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice.
33. Clinical Case Three Patient:
VM: male, 62 years old
Occupation: retired
Discussion
The patient is VM, retired gentleman, 62 years old with diabetes and hypertension.
He has never smoked.Discussion
The patient is VM, retired gentleman, 62 years old with diabetes and hypertension.
He has never smoked.
34. History VM medical history:
CABG in 1985
Several episodes of hospitalization for congestive heart failure in the past few months
Left knee pain with walking, relieved with stopping
No chest pain or dyspnea with exertion
Episode (<5 min) right facial numbness, 2 weeks prior to presentation
Discussion
VM had a history of coronary artery bypass graft (CABG) in 1985.
Over the past few months, VM has had several episodes of hospitalization for congestive heart failure.
The patient did not have chest pain or dyspnea with exertion. However, he stated that his left knee would hurt with walking more than one to two city blocks, but would be relieved with stopping for a couple of minutes.
He also reported an episode of right facial numbness 2 weeks ago that lasted less than 5 minutes.Discussion
VM had a history of coronary artery bypass graft (CABG) in 1985.
Over the past few months, VM has had several episodes of hospitalization for congestive heart failure.
The patient did not have chest pain or dyspnea with exertion. However, he stated that his left knee would hurt with walking more than one to two city blocks, but would be relieved with stopping for a couple of minutes.
He also reported an episode of right facial numbness 2 weeks ago that lasted less than 5 minutes.
35. Referral details:
Lateral ischemia with NSVT at a low workload on thallium stress test
100% proximal occlusion of the LAD, Lat Cx and RCA on cardiac catheterization
Patent grafts, but severe diffuse disease beyond touchdown of the three grafts
75% stenosis beyond the anastomosis of the SVG to Lat Cx Referral Discussion
A stress thallium test demonstrated lateral ischemia with non-sustained ventricular tachycardia (NSVT) at a low workload.
Cardiac catheterization revealed 100% proximal occlusion of the left anterior descending artery (LAD), left circumflex artery (Lat Cx), and right coronary artery (RCA).
Left internal mammary artery (LIMA)-LAD, saphenous vein graft (SVG)-RCA, and SVG-lateral branch of the Lat Cx were all patent (though the vein grafts had moderate atheroma throughout); however there was severe, diffuse distal disease beyond the touchdown of all three grafts.
Additionally, there was a discrete 75% stenosis immediately beyond the anastomosis of the SVG to Lat Cx. The patient was referred to our center as an outpatient for further management.Discussion
A stress thallium test demonstrated lateral ischemia with non-sustained ventricular tachycardia (NSVT) at a low workload.
Cardiac catheterization revealed 100% proximal occlusion of the left anterior descending artery (LAD), left circumflex artery (Lat Cx), and right coronary artery (RCA).
Left internal mammary artery (LIMA)-LAD, saphenous vein graft (SVG)-RCA, and SVG-lateral branch of the Lat Cx were all patent (though the vein grafts had moderate atheroma throughout); however there was severe, diffuse distal disease beyond the touchdown of all three grafts.
Additionally, there was a discrete 75% stenosis immediately beyond the anastomosis of the SVG to Lat Cx. The patient was referred to our center as an outpatient for further management.
36. Physical Examination (I) On referral:
BP: 170/95 mmHg
Heart rate: 78 bpm
Respiratory rate: 12 bpm
Corpulence: mildly obese
Head, eye, nose and throat (HEENT): bilateral carotid bruits
Lungs: clear to auscultation
37. Physical Examination (II) On referral:
Heart: regular rhythm and rate, no S3, 2/6 HSM at apex
Abdomen: no bruits, and no pulsatile mass
Extremities: distal pulses 2+ bilateral
Neurologic exam: intact in detail
38. Medication Current:
Furosemide: 100 mg o.d.
Nifedipine XL: 90 mg o.d.
Atenolol: 100 mg o.d.
Isosorbide mononitrate: 120 mg o.d.
ASA: 325 mg o.d.
Glipizide XL: 10 mg o.d. Note
Allergies: penicillin, captopril, and shellfish, all are listed in his medical records, but VM cannot remember details.
Note
Allergies: penicillin, captopril, and shellfish, all are listed in his medical records, but VM cannot remember details.
41. Treatment (I) What is your next step?
Answer
Angioplasty through an old, degenerated vein graft is associated with a substantial risk of distal embolization.
Furthermore, the vessel was described as having diffuse disease beyond the discrete lesion.
Thus, treatment of this lesion would not necessarily improve VM's heart failure.
Additionally VM is not an ideal surgical candidate.
The films were reviewed with an experienced cardiac surgeon, and it was felt that VM did not have suitable targets for repeat bypass.
Furthermore, the role of transmyocardial revascularization, if any, would be for relief of angina, not for treatment of ischemia, per se, or of heart failure.
A more detailed evaluation, including assessment of left ventricular function, would need to be performed before deciding on the need for transplant.
Clearly, the correct answer is 5. None of the above, need more information – as more information is required before proceeding with any invasive therapy.
Answer
Angioplasty through an old, degenerated vein graft is associated with a substantial risk of distal embolization.
Furthermore, the vessel was described as having diffuse disease beyond the discrete lesion.
Thus, treatment of this lesion would not necessarily improve VM's heart failure.
Additionally VM is not an ideal surgical candidate.
The films were reviewed with an experienced cardiac surgeon, and it was felt that VM did not have suitable targets for repeat bypass.
Furthermore, the role of transmyocardial revascularization, if any, would be for relief of angina, not for treatment of ischemia, per se, or of heart failure.
A more detailed evaluation, including assessment of left ventricular function, would need to be performed before deciding on the need for transplant.
Clearly, the correct answer is 5. None of the above, need more information – as more information is required before proceeding with any invasive therapy.
42. In this case, what are the symptoms of knee pain most likely be consistent with? Diagnosis (I) Answer
Lower extremity pain in an older patient could be due to multiple causes.
The history and physical examination are helpful, though often over time there is a need for non-invasive testing to differentiate among musculoskeletal, neurologic, and vascular causes.
While arthritis is a possibility, in this case of a man with diabetes, hypertension, and extensive coronary artery disease, the correct answer is 3. Claudication should be considered in the differential diagnosis.
Answer
Lower extremity pain in an older patient could be due to multiple causes.
The history and physical examination are helpful, though often over time there is a need for non-invasive testing to differentiate among musculoskeletal, neurologic, and vascular causes.
While arthritis is a possibility, in this case of a man with diabetes, hypertension, and extensive coronary artery disease, the correct answer is 3. Claudication should be considered in the differential diagnosis.
43. What is the most likely cause of the right facial numbness? Diagnosis (II) Answer
Answer 1. Transient ischemic attack is the most likely explanation.
The episode did not last long enough to be considered a stroke.
Seizure is a possibility worth considering, but is not high on the differential.
While people with diabetes are at increased risk of neuropathy, this transient episode of facial numbness is an unlikely manifestation of neuropathy.
Answer
Answer 1. Transient ischemic attack is the most likely explanation.
The episode did not last long enough to be considered a stroke.
Seizure is a possibility worth considering, but is not high on the differential.
While people with diabetes are at increased risk of neuropathy, this transient episode of facial numbness is an unlikely manifestation of neuropathy.
44. What are the appropriate studies to order? Investigation (III) Answer
The correct answer is 5. all three studies.
Carotid ultrasound would be important to look for carotid artery stenosis.
Echocardiography (ECHO) would be necessary to assess left ventricular function, perhaps also to screen for embolic sources.
PVRs would also be important to assess for peripheral vascular disease; importantly, the presence of palpable distal pulses does not exclude the diagnosis of peripheral arterial disease (PAD).
Answer
The correct answer is 5. all three studies.
Carotid ultrasound would be important to look for carotid artery stenosis.
Echocardiography (ECHO) would be necessary to assess left ventricular function, perhaps also to screen for embolic sources.
PVRs would also be important to assess for peripheral vascular disease; importantly, the presence of palpable distal pulses does not exclude the diagnosis of peripheral arterial disease (PAD).
45. Investigation (IV) Analysis
In additional to left ventricular hypertrophy (LVH) with diastolic dysfunction, ECHO showed a left ventricular ejection fraction (LVEH) of 45% with 2+ mitral regurgitation and moderate inferior/lateral hypokinesis.
Head computed tomography (CT) without contrast was normal.
PVRs at rest were normal.
Carotid ultrasound revealed a severe stenosis of the left internal carotid artery (LICA). Analysis
In additional to left ventricular hypertrophy (LVH) with diastolic dysfunction, ECHO showed a left ventricular ejection fraction (LVEH) of 45% with 2+ mitral regurgitation and moderate inferior/lateral hypokinesis.
Head computed tomography (CT) without contrast was normal.
PVRs at rest were normal.
Carotid ultrasound revealed a severe stenosis of the left internal carotid artery (LICA).
46. What is VM’s heart failure most likely to be due to? Diagnosis (III) Answer
At rest, neither the extent of systolic dysfunction nor the degree of mitral regurgitation can explain the patient's symptoms.
Potentially, under conditions in which VM is ischemic, either the left ventricular dysfunction or mitral regurgitation could get worse.
The correct answer is 3. Diastolic dysfunction due to LVH (+/- ischemia). This could certainly account for his frequent heart failure admissions, especially if his BP is not well controlled (noted to be 170/95 mmHg at rest); this was the impression at this point.
Answer
At rest, neither the extent of systolic dysfunction nor the degree of mitral regurgitation can explain the patient's symptoms.
Potentially, under conditions in which VM is ischemic, either the left ventricular dysfunction or mitral regurgitation could get worse.
The correct answer is 3. Diastolic dysfunction due to LVH (+/- ischemia). This could certainly account for his frequent heart failure admissions, especially if his BP is not well controlled (noted to be 170/95 mmHg at rest); this was the impression at this point.
47. Treatment (II) How should VM’s carotid stenosis be addressed?
Answer
This patient is at very high risk for carotid endarterectomy.
A functional study shows ischemia at a low workload. There have been several recent episodes of heart failure prompting hospital admission.
Few surgeons would be enthusiastic about operating on such a patient, and most would want an angiogram before proceeding.
The patient was already on ASA when the presumed TIA occurred, displaying clinical ‘ASA resistance’, thus increasing the dose is likely to increase the risk of bleeding without increasing efficacy.
Starting clopidogrel is theoretically a sound strategy and prospective studies are ongoing examining the value of combination antiplatelet therapy for cerebrovascular disease.
The correct answer is 5. Urgent carotid angiography and starting clopidogrel.*Answer
This patient is at very high risk for carotid endarterectomy.
A functional study shows ischemia at a low workload. There have been several recent episodes of heart failure prompting hospital admission.
Few surgeons would be enthusiastic about operating on such a patient, and most would want an angiogram before proceeding.
The patient was already on ASA when the presumed TIA occurred, displaying clinical ‘ASA resistance’, thus increasing the dose is likely to increase the risk of bleeding without increasing efficacy.
Starting clopidogrel is theoretically a sound strategy and prospective studies are ongoing examining the value of combination antiplatelet therapy for cerebrovascular disease.
The correct answer is 5. Urgent carotid angiography and starting clopidogrel.*
48. Do the normal PVRs exclude the diagnosis of PAD? Diagnosis (IV) Answer
The correct answer is 2. No. Normal PVRs at rest do not exclude the diagnosis of peripheral arterial disease.
If clinical history suggests claudication, post-exercise PVRs must be performed.
Though the information was not presented here, the post-exercise PVRs showed a significant drop in the ankle-brachial index (ABI).
Furthermore, the actual waveforms should be inspected and the clinical context considered.
For example, diabetics may have falsely elevated lower-extremity measurements due to calcified vessels; a toe-brachial index may be more useful than the ABI in these situations.Answer
The correct answer is 2. No. Normal PVRs at rest do not exclude the diagnosis of peripheral arterial disease.
If clinical history suggests claudication, post-exercise PVRs must be performed.
Though the information was not presented here, the post-exercise PVRs showed a significant drop in the ankle-brachial index (ABI).
Furthermore, the actual waveforms should be inspected and the clinical context considered.
For example, diabetics may have falsely elevated lower-extremity measurements due to calcified vessels; a toe-brachial index may be more useful than the ABI in these situations.
49. Investigation (V) Analysis
Abdominal aortography with runoffs were performed:
The left renal artery had a significant stenosis with a large pressure gradient across it.
The right renal artery shows a severe renal artery stenosis. Additionally, this angiographic stenosis was associated with a significant hemodynamic gradient.
Analysis
Abdominal aortography with runoffs were performed:
The left renal artery had a significant stenosis with a large pressure gradient across it.
The right renal artery shows a severe renal artery stenosis. Additionally, this angiographic stenosis was associated with a significant hemodynamic gradient.
50. Investigation (VI) Analysis
The left superficial femoral artery (SFA) has several areas of moderate atheroma. This is not uncommon in patients with peripheral vascular disease.
However, there was at least one area of severe angiographic stenosis, and hemodynamic gradient measurement allowed us to localize the most severe areas of the obstruction.
There was a severe (95%) LICA stenosis with some alterations present as well. Very likely, this stenosis accounted for the patient's recent TIA.
The angiograms confirmed the findings of the duplex ultrasounds. Analysis
The left superficial femoral artery (SFA) has several areas of moderate atheroma. This is not uncommon in patients with peripheral vascular disease.
However, there was at least one area of severe angiographic stenosis, and hemodynamic gradient measurement allowed us to localize the most severe areas of the obstruction.
There was a severe (95%) LICA stenosis with some alterations present as well. Very likely, this stenosis accounted for the patient's recent TIA.
The angiograms confirmed the findings of the duplex ultrasounds.
51. Investigation (VII) Analysis
Abdominal angiography with runoffs revealed:
severe bilateral renal artery stenosis
left SFA stenosis
95% LICA stenosis.
Analysis
Abdominal angiography with runoffs revealed:
severe bilateral renal artery stenosis
left SFA stenosis
95% LICA stenosis.
52. Treatment (III) What is the appropriate management strategy?
Answer
Consideration should be given to renal artery stenosis in the setting of recurrent pulmonary edema, as well as difficult to control high BP.
Resistance to angiotensin-converting enzyme inhibitors can be another clue.
Renal artery stenting is appropriate for bilateral renal artery stenosis in this situation.
Superficial femoral artery PTA is appropriate for symptom relief.
Carotid stenting is an investigational technique that is being compared with surgical endarterectomy.
However, in experienced centers, it may be an option for nonsurgical candidates.
Answer 4. All of the above.Answer
Consideration should be given to renal artery stenosis in the setting of recurrent pulmonary edema, as well as difficult to control high BP.
Resistance to angiotensin-converting enzyme inhibitors can be another clue.
Renal artery stenting is appropriate for bilateral renal artery stenosis in this situation.
Superficial femoral artery PTA is appropriate for symptom relief.
Carotid stenting is an investigational technique that is being compared with surgical endarterectomy.
However, in experienced centers, it may be an option for nonsurgical candidates.
Answer 4. All of the above.
53. What is the appropriate management strategy?
Treatment (IV) Discussion
VM underwent bilateral renal artery stenting, as well as stenting of the left superficial femoral artery.
He will return for carotid stenting after evaluation by a multidisciplinary team consisting of cardiologists, neurologists, and vascular surgeons.
Discussion
VM underwent bilateral renal artery stenting, as well as stenting of the left superficial femoral artery.
He will return for carotid stenting after evaluation by a multidisciplinary team consisting of cardiologists, neurologists, and vascular surgeons.
54. Follow-up (I) Analysis
The left hand figure shows the results after placement of a stent in the left renal artery.
The angiogram demonstrates brisk flow with no significant residual stenosis.
Additionally, pressure gradient measurement revealed no hemodynamic gradient.
With reference to the right hand figure, a stent was placed in the right renal artery as well.
Angiography again confirms brisk flow with no significant angiographic residual stenosis, and similar to the left renal artery, the pressure gradient was once again measured after stent deployment and revealed no gradient.
Analysis
The left hand figure shows the results after placement of a stent in the left renal artery.
The angiogram demonstrates brisk flow with no significant residual stenosis.
Additionally, pressure gradient measurement revealed no hemodynamic gradient.
With reference to the right hand figure, a stent was placed in the right renal artery as well.
Angiography again confirms brisk flow with no significant angiographic residual stenosis, and similar to the left renal artery, the pressure gradient was once again measured after stent deployment and revealed no gradient.
55. Follow-up (II) Analysis
A stent was placed in the left superficial femoral artery with a good angiographic result, while repeated angiography still showed presence of moderate atheroma through the course of the left superficial femoral artery.
Careful pressure gradient measurement through the segment revealed no significant pressure gradient at rest at least, and therefore no additional peripheral interventions were performed..
Analysis
A stent was placed in the left superficial femoral artery with a good angiographic result, while repeated angiography still showed presence of moderate atheroma through the course of the left superficial femoral artery.
Careful pressure gradient measurement through the segment revealed no significant pressure gradient at rest at least, and therefore no additional peripheral interventions were performed..
56. Treatment (V) What is the most appropriate medical management? Answer
The evidence for ASA from the Antiplatelet Trialists' Collaboration1 is strongly supportive of ASA use.
In this high-risk patient, the CAPRIE study2 would indicate that clopidogrel would be preferable to ASA, and at least as safe.
Subsequent analyses of CAPRIE suggest that patients with diabetes3 and bypass surgery4 derive marked benefit of clopidogrel over ASA in reducing myocardial infarction, stroke, vascular death, and rehospitalization for ischemia and bleeding.
Based on the data from the recent CURE trial in patients with acute coronary syndromes, the combination of ASA and clopidogrel could offer this patient enhanced antiplatelet protection.5
The benefit of statin therapy in this patient with extensive vascular disease is proven. A LDL of 100 or less should be the target.
Given the results of the HOPE trial,5 ACE inhibitor therapy is also indicated.
Therefore, the answer is 5. All of the above.*Answer
The evidence for ASA from the Antiplatelet Trialists' Collaboration1 is strongly supportive of ASA use.
In this high-risk patient, the CAPRIE study2 would indicate that clopidogrel would be preferable to ASA, and at least as safe.
Subsequent analyses of CAPRIE suggest that patients with diabetes3 and bypass surgery4 derive marked benefit of clopidogrel over ASA in reducing myocardial infarction, stroke, vascular death, and rehospitalization for ischemia and bleeding.
Based on the data from the recent CURE trial in patients with acute coronary syndromes, the combination of ASA and clopidogrel could offer this patient enhanced antiplatelet protection.5
The benefit of statin therapy in this patient with extensive vascular disease is proven. A LDL of 100 or less should be the target.
Given the results of the HOPE trial,5 ACE inhibitor therapy is also indicated.
Therefore, the answer is 5. All of the above.*
57. Treatment (VI) On discharge:
ASA: 325 mg o.d.
Clopidogrel: 75 mg o.d.
Atorvastatin: 10 mg o.d.
Ramipril: 2.5 mg o.d. (increased after BP evaluation at 1 week)
Diuretic: discontinued
Nitrate: continued (with possibility of future dose increase)
Beta blocker: continued (with possibility of future dose increase) Discussion
VM was sent home on:
ASA 325 mg o.d. and clopidogrel 75 mg o.d.
atorvastatin 10 mg o.d. was started
ramipril 2.5 mg o.d. was started; blood pressure was rechecked in a week, and the dose of ramipril was increased at that time
the diuretic was discontinued, the nitrate and the beta blocker were continued, with consideration of increasing the doses in the future.Discussion
VM was sent home on:
ASA 325 mg o.d. and clopidogrel 75 mg o.d.
atorvastatin 10 mg o.d. was started
ramipril 2.5 mg o.d. was started; blood pressure was rechecked in a week, and the dose of ramipril was increased at that time
the diuretic was discontinued, the nitrate and the beta blocker were continued, with consideration of increasing the doses in the future.
58. Treatment (VII) Lifestyle program:
Maintain a log book of blood glucose values
Start walking program
Additional interventions proposed:
LICA stenting with emboli protection Discussion
VM was instructed to maintain a log book of blood glucose values, start a walking program and notify his physicians if he should develop angina with his anticipated greater degree of physical exertion.
As he was high risk for surgical endarterectomy, he was offered the option of carotid stenting as part of an Institutional Review Board-approved registry.
The patient discussed the possibility of carotid stenting with his local doctors and decided to return for the procedure in 2 weeks. His blood pressure was under good control at the time of his return visit and he had not experienced any angina. Discussion
VM was instructed to maintain a log book of blood glucose values, start a walking program and notify his physicians if he should develop angina with his anticipated greater degree of physical exertion.
As he was high risk for surgical endarterectomy, he was offered the option of carotid stenting as part of an Institutional Review Board-approved registry.
The patient discussed the possibility of carotid stenting with his local doctors and decided to return for the procedure in 2 weeks. His blood pressure was under good control at the time of his return visit and he had not experienced any angina.
59. Follow-up (III) Analysis
VM underwent carotid stenting with emboli protection with excellent result and was discharged home uneventfully the next day.
This figure shows the angiogram after placement of a self-expanding nitinol stent in the LICA.
An emboli protection device was used and the case was performed without complication.
The angiogram demonstrates brisk flow, and while there is some residual stenosis in this situation, it is not necessary to obtain a perfect angiographic lumen, but rather to sufficiently cover this diseased area and prevent future embolic events and TIAs.
There is an adequate lumen in terms of antegrade flow and hemodynamic factors, and therefore trying to obtain an even larger lumen with the self-expanding stent would probably risk emboli even with the use of an emboli-protection device.
At this point with the angiographic results were considered satisfactory and the procedure was terminated. Analysis
VM underwent carotid stenting with emboli protection with excellent result and was discharged home uneventfully the next day.
This figure shows the angiogram after placement of a self-expanding nitinol stent in the LICA.
An emboli protection device was used and the case was performed without complication.
The angiogram demonstrates brisk flow, and while there is some residual stenosis in this situation, it is not necessary to obtain a perfect angiographic lumen, but rather to sufficiently cover this diseased area and prevent future embolic events and TIAs.
There is an adequate lumen in terms of antegrade flow and hemodynamic factors, and therefore trying to obtain an even larger lumen with the self-expanding stent would probably risk emboli even with the use of an emboli-protection device.
At this point with the angiographic results were considered satisfactory and the procedure was terminated.
60. Conclusion
This patient with polyvascular disease was quite a difficult case as there were several ways that he could have been managed, all of which would have been acceptable. It was our philosophy that the best way of treating this patient was a combination of optimizing his medical therapy in terms of antiplatelet therapy with ASA and clopidogrel, stenting therapy, the use of ACE inhibitors, and the use of beta blockers.
However, in addition to maximizing his medical therapy, it is important to try to decrease the chance of recurrent ischemic events as far as his carotid artery stenosis, by using percutaneous intervention. It is also vital to try to reduce the chances of him having a flash pulmonary edema again by treating his bilateral renal artery stenosis.
His quality of life could be improved with treatment of his superficial femoral artery stenosis, through a combination of aggressive medical management and interventional procedures.
He still has extensive vascular disease, especially with his coronary arteries that have not been addressed through revascularization. Hopefully, the aggressive medical regimen that was started will help him to remain healthy.
This patient will need to be followed closely and remains at risk of further ischemic events, but at least with the measures taken his local doctors will be able to minimize the chances of him having recurrence of disease in any of his arterial territories.
Conclusion
This patient with polyvascular disease was quite a difficult case as there were several ways that he could have been managed, all of which would have been acceptable. It was our philosophy that the best way of treating this patient was a combination of optimizing his medical therapy in terms of antiplatelet therapy with ASA and clopidogrel, stenting therapy, the use of ACE inhibitors, and the use of beta blockers.
However, in addition to maximizing his medical therapy, it is important to try to decrease the chance of recurrent ischemic events as far as his carotid artery stenosis, by using percutaneous intervention. It is also vital to try to reduce the chances of him having a flash pulmonary edema again by treating his bilateral renal artery stenosis.
His quality of life could be improved with treatment of his superficial femoral artery stenosis, through a combination of aggressive medical management and interventional procedures.
He still has extensive vascular disease, especially with his coronary arteries that have not been addressed through revascularization. Hopefully, the aggressive medical regimen that was started will help him to remain healthy.
This patient will need to be followed closely and remains at risk of further ischemic events, but at least with the measures taken his local doctors will be able to minimize the chances of him having recurrence of disease in any of his arterial territories.
61. Atherothrombosis Management in Practice – Clinical Cases Clinical Case Four This slide kit contains four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice. This slide kit contains four clinical cases, which have been prepared to facilitate discussion amongst clinicians about the management of atherothrombosis in practice.
62. Clinical Case Four Patient:
FB: male, 64 years old
63. Background FB medical history:
Smoked 1 pack/day for 40 years
Hypertension: 10 years
Myocardial infarction (MI) at age 58
Minor stroke at age 60, while taking ASA
Medications include:
ASA
atenolol
captopril
ticlopidine tried following his stroke, but was discontinued because of persistent diarrhea
64. On presentation:
Height: 6’ 0" (1.83 m)
Weight: 196 lb (89.0 kg)
BP: 154/88 mmHg
Pulse: 68 bpm and regular
Carotid arteries: no bruits
Heart: no murmurs
Neurologic: post stroke 4 years ago
slight left-sided clumsiness and hyperreflexia
dysarthria
otherwise, normal
Physical Examination (I)
65. Investigation (I)
66. Investigation (II)
67. Diagnosis In summary, FB has multi-system atherosclerosis
He has multiple clinical manifestations of this problem and multiple risk factors, including:
68. Investigation (III) What is the most appropriate diagnostic test, to exclude a small intracerebral hemorrhage, a brain tumor, or other brain disease masquerading as a TIA?
Answer
FB’s history is typical for a TIA.
He has multiple atherosclerosis risk factors and his clinical risk profile fits also – that is, his prior history of coronary and cerebral artery ischemia.
Also, there's nothing in his history to suggest malignancy, subdural hematoma, seizure, and so forth.
Thus it would be reasonable to obtain a plain CT of the brain simply to exclude hemorrhage or a surprise abnormality.
An MR scan would provide even more information but the cost in scheduling time, imaging time and expense are often excessive.
Contrast arteriography is expensive, time consuming, and carries a risk of harming the patient. It's not really indicated unless screening tests show an abnormality that requires contrast arteriography for further assessment.
Therefore, the correct answer is 1. Computed tomography (CT) scan.
However, in many countries where imaging studies are not readily available, or are prohibitively expensive, clinicians rely on their history and physical examination alone to make the correct diagnosis.
Answer
FB’s history is typical for a TIA.
He has multiple atherosclerosis risk factors and his clinical risk profile fits also – that is, his prior history of coronary and cerebral artery ischemia.
Also, there's nothing in his history to suggest malignancy, subdural hematoma, seizure, and so forth.
Thus it would be reasonable to obtain a plain CT of the brain simply to exclude hemorrhage or a surprise abnormality.
An MR scan would provide even more information but the cost in scheduling time, imaging time and expense are often excessive.
Contrast arteriography is expensive, time consuming, and carries a risk of harming the patient. It's not really indicated unless screening tests show an abnormality that requires contrast arteriography for further assessment.
Therefore, the correct answer is 1. Computed tomography (CT) scan.
However, in many countries where imaging studies are not readily available, or are prohibitively expensive, clinicians rely on their history and physical examination alone to make the correct diagnosis.
69. Investigation (IV) Analysis
The CT shows an old lacunar infarct (< 1 cm in diameter) in the right internal capsule and patchy hypodensities (leukoaraiosis) in the deep white matter of the cerebral hemispheres and brainstem.
Analysis
The CT shows an old lacunar infarct (< 1 cm in diameter) in the right internal capsule and patchy hypodensities (leukoaraiosis) in the deep white matter of the cerebral hemispheres and brainstem.
70. Investigation (V) Which test(s) are appropriate to further evaluate this patient's cerebral circulation? Answer
Ultrasound of the cervical and cerebral arteries, magnetic resonance arteriography (MRA), and conventional intra-arterial contrast arteriography all are valuable in assessing the cause of cerebral vascular disease (answer 5.).
FB’s ischemia was most likely in the left carotid artery distribution. A primary question is whether he has a high-grade stenosis in the left cervical carotid artery that makes him a candidate for carotid endarterectomy. If he has a > 70% stenosis, especially with his several medical risk factors, he generally should have a carotid endarterectomy. If he has a 50–70% stenosis, the benefits from endarterectomy are controversial.
Properly done duplex ultrasound and high-resolution MRA are both capable of determining if important stenoses are present. The reliability of the tests varies in different institutions and all of the large clinical trials that evaluated carotid endarterectomy used contrast arteriography as the gold standard. Either a duplex ultrasound or MRA should probably be carried out and if an important stenosis is found it should be confirmed by conventional intra-arterial contrast arteriography.
Some experts believe that patients with intracranial arterial stenoses > 50% should be treated with anticoagulation rather than antiplatelet therapy. These clinicians generally obtain an imaging study (transcranial Doppler ultrasound or intracranial MR angiography) and if an important stenosis is found they confirmit by conventional intra-arterial contrast arteriography. Others are unconvinced that anticoagulation is better than antiplatelet therapy, so they do not obtain intracranial arterial studies. The Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial is in progress and should resolve this uncertainty.
Answer
Ultrasound of the cervical and cerebral arteries, magnetic resonance arteriography (MRA), and conventional intra-arterial contrast arteriography all are valuable in assessing the cause of cerebral vascular disease (answer 5.).
FB’s ischemia was most likely in the left carotid artery distribution. A primary question is whether he has a high-grade stenosis in the left cervical carotid artery that makes him a candidate for carotid endarterectomy. If he has a > 70% stenosis, especially with his several medical risk factors, he generally should have a carotid endarterectomy. If he has a 50–70% stenosis, the benefits from endarterectomy are controversial.
Properly done duplex ultrasound and high-resolution MRA are both capable of determining if important stenoses are present. The reliability of the tests varies in different institutions and all of the large clinical trials that evaluated carotid endarterectomy used contrast arteriography as the gold standard. Either a duplex ultrasound or MRA should probably be carried out and if an important stenosis is found it should be confirmed by conventional intra-arterial contrast arteriography.
Some experts believe that patients with intracranial arterial stenoses > 50% should be treated with anticoagulation rather than antiplatelet therapy. These clinicians generally obtain an imaging study (transcranial Doppler ultrasound or intracranial MR angiography) and if an important stenosis is found they confirmit by conventional intra-arterial contrast arteriography. Others are unconvinced that anticoagulation is better than antiplatelet therapy, so they do not obtain intracranial arterial studies. The Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial is in progress and should resolve this uncertainty.
71. Investigation (VI) Analysis
FB’s MR angiogram was normal and showed neither intracranial nor extracranial disease, so there is no need to pursue that evaluation further.
Analysis
FB’s MR angiogram was normal and showed neither intracranial nor extracranial disease, so there is no need to pursue that evaluation further.
72. Investigation (VII) Which of the following tests should be considered to further evaluate FB’s heart and aorta, as sources of embolism?
Answer
If there were no history of cardiac disease, and a normal heart on physical and ECG examination, the yield from Holter monitoring and echocardiography (ECHO) would be extremely low, and testing would not be warranted.
However, FB had a MI, so a Holter monitor, in this case looking for paroxysmal atrial fibrillation, and an ECHO to assess his left ventricular function, would be advisable (answer 7.).
Large mobile atherosclerotic plaques and thrombi probably cause many ischemic strokes. It is not clear how such lesions should be treated so many experts do not look for them. This is clearly a work in progress. Answer
If there were no history of cardiac disease, and a normal heart on physical and ECG examination, the yield from Holter monitoring and echocardiography (ECHO) would be extremely low, and testing would not be warranted.
However, FB had a MI, so a Holter monitor, in this case looking for paroxysmal atrial fibrillation, and an ECHO to assess his left ventricular function, would be advisable (answer 7.).
Large mobile atherosclerotic plaques and thrombi probably cause many ischemic strokes. It is not clear how such lesions should be treated so many experts do not look for them. This is clearly a work in progress.
73. Treatment (I) What is the appropriate treatment for this patient? Answer
FB needs to stop smoking . He should be referred to a smoking cessation program for help.
Hypertension is one of the most potent risk factors for stroke. FB’s blood pressure of 154/88 mmHg is too high. It should be lowered to the range of 130±10 over 75± 5, if this can be achieved without symptoms of hypotension, or other unacceptable side effects.
The patchy hypodensities in the deep white matter of the cerebral hemispheres and brainstem, as seen on his scan, are caused by ischemia due to microvascular arteriolar disease that occurs with aging, hypertension, and perhaps, smoking and diabetes.
The more aggressive use of an angiotensin converting enzyme (ACE) inhibitor would be wise. ACE inhibitors appear to reduce atherothrombotic outcomes, over and above their antihypertension effect.
He probably should be treated with a statin also. His LDL cholesterol is high and his HDL cholesterol is low.
Clearly his diet should be optimized to lower his serum cholesterol. However, like ACE inhibitors, statins appear to confer benefit for prevention of atherothrombosis, over and above their lipid-lowering effect.
The same appears to be true for stroke prevention though the evidence supporting this view is less robust. Clinical trials to assess their benefit in stroke prevention are in progress.
Antiplatelet therapy should be initiated to reduce the risk of future ischemic events in the cerebral and other vascular beds.
Answer
FB needs to stop smoking . He should be referred to a smoking cessation program for help.
Hypertension is one of the most potent risk factors for stroke. FB’s blood pressure of 154/88 mmHg is too high. It should be lowered to the range of 130±10 over 75± 5, if this can be achieved without symptoms of hypotension, or other unacceptable side effects.
The patchy hypodensities in the deep white matter of the cerebral hemispheres and brainstem, as seen on his scan, are caused by ischemia due to microvascular arteriolar disease that occurs with aging, hypertension, and perhaps, smoking and diabetes.
The more aggressive use of an angiotensin converting enzyme (ACE) inhibitor would be wise. ACE inhibitors appear to reduce atherothrombotic outcomes, over and above their antihypertension effect.
He probably should be treated with a statin also. His LDL cholesterol is high and his HDL cholesterol is low.
Clearly his diet should be optimized to lower his serum cholesterol. However, like ACE inhibitors, statins appear to confer benefit for prevention of atherothrombosis, over and above their lipid-lowering effect.
The same appears to be true for stroke prevention though the evidence supporting this view is less robust. Clinical trials to assess their benefit in stroke prevention are in progress.
Antiplatelet therapy should be initiated to reduce the risk of future ischemic events in the cerebral and other vascular beds.
74. Treatment (II) Which of the following antiplatelet therapies is the most appropriate in this case?
Answer
ASA, ticlopidine, clopidogrel and ASA plus extended-release dipyridamole (Aggrenox) are widely approved for stroke prevention. All of them reduce the risk of ischemic stroke but none of them completely eliminate the risk.1,2
FB has had 2 cerebral ishcemic events while on ASA, and he did not tolerate ticlopidine.
Aggrenox is more effective than ASA alone in reducing the risk of stroke, but it does not appear to reduce MI or death.3
FB is at substantial risk for MI, as well as stroke. Thus the preferred choice of antiplatelet therapy is clopidogrel. It's well tolerated and it reduces the risk of stroke, MI, and vascular death by about 9% over ASA. Evidence from the Canadian-American Ticlopidine Study (CATS)4 and the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE)5 Trial suggest both small and large artery cerebral disease benefit about equally from thienopyridines.
The benefit of long-term use of either ticlopidine or clopidogrel combined with ASA in cerebrovascular manifestations of atherothrombosis is currently unstudied and unapproved. However, both thienopyridines are substantially more effective than ASA alone in reducing atherothrombotic outcomes in patients with coronary angioplasty and stenting,6 and in patients with acute coronary syndromes (without ST segment elevation).7 However, with clopidogrel's superior safety profile over ticlopidine, when they are combined with ASA, the preferred option is clopidogrel.6 Consequently, many neurologists use the combination of ASA and clopidogrel in patients at high risk for stroke who have had events while on other drugs alone.
A number of clinical trials to assess the benefit of the combination of clopidogrel and ASA in prevention of atherothrombosis are in progress.Answer
ASA, ticlopidine, clopidogrel and ASA plus extended-release dipyridamole (Aggrenox) are widely approved for stroke prevention. All of them reduce the risk of ischemic stroke but none of them completely eliminate the risk.1,2
FB has had 2 cerebral ishcemic events while on ASA, and he did not tolerate ticlopidine.
Aggrenox is more effective than ASA alone in reducing the risk of stroke, but it does not appear to reduce MI or death.3
FB is at substantial risk for MI, as well as stroke. Thus the preferred choice of antiplatelet therapy is clopidogrel. It's well tolerated and it reduces the risk of stroke, MI, and vascular death by about 9% over ASA. Evidence from the Canadian-American Ticlopidine Study (CATS)4 and the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE)5 Trial suggest both small and large artery cerebral disease benefit about equally from thienopyridines.
The benefit of long-term use of either ticlopidine or clopidogrel combined with ASA in cerebrovascular manifestations of atherothrombosis is currently unstudied and unapproved. However, both thienopyridines are substantially more effective than ASA alone in reducing atherothrombotic outcomes in patients with coronary angioplasty and stenting,6 and in patients with acute coronary syndromes (without ST segment elevation).7 However, with clopidogrel's superior safety profile over ticlopidine, when they are combined with ASA, the preferred option is clopidogrel.6 Consequently, many neurologists use the combination of ASA and clopidogrel in patients at high risk for stroke who have had events while on other drugs alone.
A number of clinical trials to assess the benefit of the combination of clopidogrel and ASA in prevention of atherothrombosis are in progress.
75. Disclaimer These clinical patient cases represent model cases, expressing the views of the authors, only. All patients should be evaluated based upon their personal clinical history.
The slide kit has been prepared for medical and scientific purposes, and cannot be considered as an inducement to use clopidogrel in non-registered indications.
Neither Sanofi-Synthélabo nor Bristol-Myers Squibb recommends the use of clopidogrel in any manner inconsistent with that described in the full prescribing information.
