562
that lowered blood pressure (systolic/diastolic) by 5/4 Hg, the enalapril-treated patients had a substantially and significantly reduced incidence of unstable angina and myocardial infarction. The patients in these studies are exactly those who should be especially at risk in the J-curve hypothesis which seems to operate independent of LV function.2 Yet reducing diastolic blood pressure to around 73 mm Hg did these patients no harm. Perhaps the critical diastolic pressure in the J-curve mechanism needs further downward adjustment, or perhaps the J-curve might be best forgotten? treatment
mm
Department of Cardiology and University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK
JOHN MCMURRAY GORDON T. MCINNES
1. Cruickshank JM, Thorp JM, Zacharias FJ. Benefits and potential harm of lowering high blood pressure. Lancet 1987; i: 581-84. 2. D’Agostino RB, Belanger AJ, Kannell WB, Cruickshank JM. Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study. Br Med J 1991; 303: 385-89. 3. The SOLVD Investigators. Studies of left ventricular dysfunction (SOLVD), rationale, design and methods: two trials that evaluate the effect of enalapril in patients with reduced ejection fraction. Am J Cardiol 1990; 66: 315-22 4. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302. 5. The SOLVD Investigators. Initial blood pressure response to enalapril in hospitalised patients. (Studies of Left Ventricular Dysfunction [SOLVD]). Am J Cardiol 1991; 68: 1465-67. 6. SOLVD Prevention Arm: unpublished results presented to American Heart Association. November, 1991.
Does thrombolysis produce cholesterol embolisation? SIR,-Microembolisation of cholesterol crystals from ruptured atherosclerotic aortic plaques may produce a multisystem disease with variable clinical manifestations and high mortality.1 Cholesterol embolisation can occur spontaneously, or after aortic surgery or major vessel angiography in severely atherosclerotic aorta.In some cases anticoagulants are involved in this process, but only few are related to thrombolysis.2-4 We report a 64-year-old white man, with a recent history of non-Q-wave anterior myocardial infarction. He was treated with intravenous streptokinase 1500 000 IU for enduring chest pain with electrocardiographic signs of acute transmural anterior ischaemia. Thrombolysis was successful and no signs of new myocardial infarction developed. Coronary angiography showed critical stenosis of three vessels of the left main coronary artery. He was referred for elective aortocoronary bypass graft and discharged on treatment with verapamil 240 mg per day, transdermal nitroglycerine disc 15 mg per day, heparin 5000 units per day subcutaneously. 1 month later he was readmitted because of acute renal failure. He had an arterial blood pressure of 180/110 mm Hg with grade 3 hypertensive retinopathy. Peripheral arterial pulses were bilaterally decreased, and he had cyanosis of the distal phalanx of the left-hand fingers and of the 4th and 5th toe of the left foot. Limbs were cool and the skin of the left leg had a livedo reticularis pattern. Lungs were clear to auscultation and cardiac examination was normal. Abdominal and aortic sonography was unremarkable. Left gastrocnemius muscle and skin biopsy demonstrated cholesterol embolisation and concentric fibrosis of a small artery of the skin. The patient’s status further deteriorated; he was successfully treated with intermittent haemodialysis. The diagnosis of atheroembolic renal disease was based on the appearance of clinical features such as livedo reticularis, peripheral ischaemia, hypertension, leucocytosis and progressive renal failure after thrombolysis, coronary angiography, and anticoagulation with heparin, in the recorded sequence. Unlike major vessel angiography, the role of anticoagulant or thrombolytic therapy in cholesterol embolisation is controversial. Some workers postulated that anticoagulants’ and thrombolytic agents3,4 might promote embolisation, by preventing thrombus formation or destabilising a thrombus over ulcerating atheromatous plaques and favouring continous dissemination of atheromatous fragments into the peripheral circulation.
Atheroembolisation is a cause of major clinical complications," but it has not been mentioned in reports of major thrombolytic trials.5 In these trials, at least some of the reported cases of renal vasculitis and glomerulonephritis could also be related to unrecognised cholesterol embolisation. This has been described as a .6 direct cause of necrotising glomerulonephritis As Smith et all suggested, the clinical manifestations of atheroembolism are fortunately far less frequent than expected on the base of the histological findings. We suggest that thrombolysis should be included in the causative factors or cholesterol embolisation. Because of the long time course of renal cholesterol embolisation after angiography and/or thrombolysis, which we have also seen, it seems advisable to check renal function one to six weeks after thrombolysis and coronary angiography, or during anticoagulation. Equally important, the clinical status of the patient should be carefully observed for 1-2 months after treatment. Departments of Cardiology, Nephrology, and Pathology, Fatebenefratelli and Oftalmico Hospitals, 20123 Milan, Italy
R. MENDIA G. CAVALIERE F. SPARACIO F. M. TURAZZA
G. D’ALOYA M. G. PALMERI
G. SORGATO G. P. SANNA
1. Smith MC, Ghose MK, Henry AR. The clinical spectrum of renal cholesterol embolization. Am J Med 1981; 71: 174-80. 2. Ikram S, Lewis S, Bucknall C, et al. Treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex. Br Med J 1986, 293: 786-89. 3. Shapiro LS. Cholesterol embolisation after treatment with tissue plasminogen activator. N Engl J Med 1989; 321: 1270. 4. Pochmalicki G, Feldman L, Meunier P, Rougeot C, Weschler J, Jan F Cholesterol embolisation syndrome after thrombolytic therapy for myocardial infarction Lancet 1992; 339: 58-59. 5. Gruppo Italiano per lo Studio Della Streptokinasi nell’infarto Miocardico Acuto (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; i: 397-402. 6. Goldman M, Thoua Y, Dhaene M, Toussaint C. Necrotising glomerulonephntis associated with cholesterol microemboli. Br MedJ 1985; 290: 205-06.
Fragmentation of pulmonary embolus SIR,-Dr Brady and colleagues’ technique (Nov 9, p 1186) opens successful, and they are to be commended. However, some points need clarification. Brady et al state that "pressure monitoring and contrast angiography are ’luxuries’". How else can we determine the success of the procedure? We do not think that we can be certain of localising and crossing the obstruction without the help of a simple initial angiogram at least.2 Specificity of diagnosis of pulmonary embolism by clinical examination, electrocardiography, and chest radiography is poorand in the absence of classic features, which were present in Brady and colleagues’ 3 patients (tablet taking, surgery, immobilisation, smoking), and without angiography can one blindly catheterise sick, shocked patients ?2,3 Use of an arm vein does not really obviate the need for a venesection since percutaneous procedure may be difficult in obese sick individuals (those most susceptible to pulmonary embolism) who have already had intravenous lines. The risk of cannulating the subclavian vein in a severely tachypnoeic patient needs to be carefully considered. Do Brady et al suggest that this method totally obviates the need for thrombolysis? What if pulmonary embolism were to recur in the acute setting? Should we repeat the same procedure or thrombolysis? Can this method be used for emboli in the main pulmonary trunk? Lastly, with respect to availability of catheters, even established centres occasionally have difficulties in emergencies. Thrombolysis seems less expensive for the general population. up many options, if it is
Department of Cardiology, SGPGIMS, PO Box 375,
K. PRASAD S. RADHAKRISHNAN
Lucknow 226 001, India
1. Brady AJB, Crake T, Oakley CM. Percutaneous fragmentation and distal dispersion of pulmonary embolus. Lancet 1991; 338: 1186-89. 2 Goldhaber SR, Braunwald E. Pulmonary embolism. In. Braunwald E, ed. Heart disease. Philadelphia: Saunders, 1988: 1577-96. 3. Bell
WR, Simon TL, DeMets DL The clinical features of submassive and massive
pulmonary emboli Am J Med 1977; 62:
355-61.
that lowered blood pressure (systolic/diastolic) by 5/4 Hg, the enalapril-treated patients had a substantially and significantly reduced incidence of unstable angina and myocardial infarction. The patients in these studies are exactly those who should be especially at risk in the J-curve hypothesis which seems to operate independent of LV function.2 Yet reducing diastolic blood pressure to around 73 mm Hg did these patients no harm. Perhaps the critical diastolic pressure in the J-curve mechanism needs further downward adjustment, or perhaps the J-curve might be best forgotten? treatment
mm
Department of Cardiology and University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK
JOHN MCMURRAY GORDON T. MCINNES
1. Cruickshank JM, Thorp JM, Zacharias FJ. Benefits and potential harm of lowering high blood pressure. Lancet 1987; i: 581-84. 2. D’Agostino RB, Belanger AJ, Kannell WB, Cruickshank JM. Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study. Br Med J 1991; 303: 385-89. 3. The SOLVD Investigators. Studies of left ventricular dysfunction (SOLVD), rationale, design and methods: two trials that evaluate the effect of enalapril in patients with reduced ejection fraction. Am J Cardiol 1990; 66: 315-22 4. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302. 5. The SOLVD Investigators. Initial blood pressure response to enalapril in hospitalised patients. (Studies of Left Ventricular Dysfunction [SOLVD]). Am J Cardiol 1991; 68: 1465-67. 6. SOLVD Prevention Arm: unpublished results presented to American Heart Association. November, 1991.
Does thrombolysis produce cholesterol embolisation? SIR,-Microembolisation of cholesterol crystals from ruptured atherosclerotic aortic plaques may produce a multisystem disease with variable clinical manifestations and high mortality.1 Cholesterol embolisation can occur spontaneously, or after aortic surgery or major vessel angiography in severely atherosclerotic aorta.In some cases anticoagulants are involved in this process, but only few are related to thrombolysis.2-4 We report a 64-year-old white man, with a recent history of non-Q-wave anterior myocardial infarction. He was treated with intravenous streptokinase 1500 000 IU for enduring chest pain with electrocardiographic signs of acute transmural anterior ischaemia. Thrombolysis was successful and no signs of new myocardial infarction developed. Coronary angiography showed critical stenosis of three vessels of the left main coronary artery. He was referred for elective aortocoronary bypass graft and discharged on treatment with verapamil 240 mg per day, transdermal nitroglycerine disc 15 mg per day, heparin 5000 units per day subcutaneously. 1 month later he was readmitted because of acute renal failure. He had an arterial blood pressure of 180/110 mm Hg with grade 3 hypertensive retinopathy. Peripheral arterial pulses were bilaterally decreased, and he had cyanosis of the distal phalanx of the left-hand fingers and of the 4th and 5th toe of the left foot. Limbs were cool and the skin of the left leg had a livedo reticularis pattern. Lungs were clear to auscultation and cardiac examination was normal. Abdominal and aortic sonography was unremarkable. Left gastrocnemius muscle and skin biopsy demonstrated cholesterol embolisation and concentric fibrosis of a small artery of the skin. The patient’s status further deteriorated; he was successfully treated with intermittent haemodialysis. The diagnosis of atheroembolic renal disease was based on the appearance of clinical features such as livedo reticularis, peripheral ischaemia, hypertension, leucocytosis and progressive renal failure after thrombolysis, coronary angiography, and anticoagulation with heparin, in the recorded sequence. Unlike major vessel angiography, the role of anticoagulant or thrombolytic therapy in cholesterol embolisation is controversial. Some workers postulated that anticoagulants’ and thrombolytic agents3,4 might promote embolisation, by preventing thrombus formation or destabilising a thrombus over ulcerating atheromatous plaques and favouring continous dissemination of atheromatous fragments into the peripheral circulation.
Atheroembolisation is a cause of major clinical complications," but it has not been mentioned in reports of major thrombolytic trials.5 In these trials, at least some of the reported cases of renal vasculitis and glomerulonephritis could also be related to unrecognised cholesterol embolisation. This has been described as a .6 direct cause of necrotising glomerulonephritis As Smith et all suggested, the clinical manifestations of atheroembolism are fortunately far less frequent than expected on the base of the histological findings. We suggest that thrombolysis should be included in the causative factors or cholesterol embolisation. Because of the long time course of renal cholesterol embolisation after angiography and/or thrombolysis, which we have also seen, it seems advisable to check renal function one to six weeks after thrombolysis and coronary angiography, or during anticoagulation. Equally important, the clinical status of the patient should be carefully observed for 1-2 months after treatment. Departments of Cardiology, Nephrology, and Pathology, Fatebenefratelli and Oftalmico Hospitals, 20123 Milan, Italy
R. MENDIA G. CAVALIERE F. SPARACIO F. M. TURAZZA
G. D’ALOYA M. G. PALMERI
G. SORGATO G. P. SANNA
1. Smith MC, Ghose MK, Henry AR. The clinical spectrum of renal cholesterol embolization. Am J Med 1981; 71: 174-80. 2. Ikram S, Lewis S, Bucknall C, et al. Treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex. Br Med J 1986, 293: 786-89. 3. Shapiro LS. Cholesterol embolisation after treatment with tissue plasminogen activator. N Engl J Med 1989; 321: 1270. 4. Pochmalicki G, Feldman L, Meunier P, Rougeot C, Weschler J, Jan F Cholesterol embolisation syndrome after thrombolytic therapy for myocardial infarction Lancet 1992; 339: 58-59. 5. Gruppo Italiano per lo Studio Della Streptokinasi nell’infarto Miocardico Acuto (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; i: 397-402. 6. Goldman M, Thoua Y, Dhaene M, Toussaint C. Necrotising glomerulonephntis associated with cholesterol microemboli. Br MedJ 1985; 290: 205-06.
Fragmentation of pulmonary embolus SIR,-Dr Brady and colleagues’ technique (Nov 9, p 1186) opens successful, and they are to be commended. However, some points need clarification. Brady et al state that "pressure monitoring and contrast angiography are ’luxuries’". How else can we determine the success of the procedure? We do not think that we can be certain of localising and crossing the obstruction without the help of a simple initial angiogram at least.2 Specificity of diagnosis of pulmonary embolism by clinical examination, electrocardiography, and chest radiography is poorand in the absence of classic features, which were present in Brady and colleagues’ 3 patients (tablet taking, surgery, immobilisation, smoking), and without angiography can one blindly catheterise sick, shocked patients ?2,3 Use of an arm vein does not really obviate the need for a venesection since percutaneous procedure may be difficult in obese sick individuals (those most susceptible to pulmonary embolism) who have already had intravenous lines. The risk of cannulating the subclavian vein in a severely tachypnoeic patient needs to be carefully considered. Do Brady et al suggest that this method totally obviates the need for thrombolysis? What if pulmonary embolism were to recur in the acute setting? Should we repeat the same procedure or thrombolysis? Can this method be used for emboli in the main pulmonary trunk? Lastly, with respect to availability of catheters, even established centres occasionally have difficulties in emergencies. Thrombolysis seems less expensive for the general population. up many options, if it is
Department of Cardiology, SGPGIMS, PO Box 375,
K. PRASAD S. RADHAKRISHNAN
Lucknow 226 001, India
1. Brady AJB, Crake T, Oakley CM. Percutaneous fragmentation and distal dispersion of pulmonary embolus. Lancet 1991; 338: 1186-89. 2 Goldhaber SR, Braunwald E. Pulmonary embolism. In. Braunwald E, ed. Heart disease. Philadelphia: Saunders, 1988: 1577-96. 3. Bell
WR, Simon TL, DeMets DL The clinical features of submassive and massive
pulmonary emboli Am J Med 1977; 62:
355-61.
