European Heart Journal (1992) 13 {Supplement H), 70-75
The natural history of angiographically demonstrated coronary artery disease A. V. G. BRUSCHKE, E. E. VAN DER WALL AND V. MANGER CATS
University Hospital, Leiden, The Netherlands KEY WORDS: Aircrew licensing, aviation, natural history, coronary artery.
Introduction
In spite of these limitations, the first large studies that appeared in the literature of the early 1970s (about 15 years after Sones had introduced the technique of selective coronary arteriography) showed surprisingly good correlations between angiographic findings and clinical followup data'2"51. At that time coronary bypass surgery had just started, catheter interventions had still to be developed, and medical management of myocardial infarction and left ventricular failure was not nearly as effective as it is today. Currently, mechanical and pharmacological interventions are common practice in patients with coronary artery disease and interfere with the 'natural history'. Indeed, as Proudfit wrote: 'It is the function of the physician to make the history as desirably unnatural as possible'161. Admitting that it is neither feasible nor ethical to study the true natural history of coronary atherosclerosis we will for practical purposes redefine natural history as 'the clinical evolution in patients who before or during the Correspondrncc: A. V. G. Bruschke, University Hospital, Department of Cardiology, Building I, C5-P, Postbus 9600, 2300 RC Leiden, The Netherlands. 0I95-668X 92 OH0070 + 06S08.00-0
Prognostic significance of a normal or slightly to moderately abnormal coronary arteriogram To assess the true prognostic value of the coronary arteriogram, patients with cardiac abnormalities other than coronary artery disease should be excluded. This may be difficult to achieve. It is in particular difficult to exclude changes of the microcirculation if the coronary arteriogram does not show haemodynamically significant obstructions. Coronary arteriography under optimal conditions allows visualization of vessels with diameters down to about 0-5 mm, but in practice it is often impossible to demonstrate changes in vessels with diameters less than 1 mm'71. It has been postulated that a substantial proportion of patients undergoing coronary arteriography for angina pectoris or angina-like symptoms and whose coronary arteriograms appear to be free of atherosclerotic changes in fact have obstructions in the small coronary vessels as may be inferred from a reduced coronary flow reserve18"'01. Small vessel coronary artery disease has been clearly demonstrated to occur in a variety of diseases'"1, however, it is uncertain if it is present in a significant proportion of the patients who have symptoms or other evidence suggesting coronary artery disease in association with a normal coronary arteriogram. Proudfit el al. found in a follow-up study that patients with normal coronary arteriograms or minimal disease had a 10-year survival from coronary disease of 99-2%, which was better than survival for the general population © 1992 The European Society of Cardiology
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
Coronary arteriography is still the only diagnostic method which allows accurate assessment of the anatomical changes caused by coronary atherosclerosis. Therefore it seems logical to base studies on the natural history of coronary atherosclerosis on findings at coronary arteriography. However, this approach is also subject to considerable, and to a certain extent insurmountable, problems. It is not feasible to study entire populations or large groups of sequential patients with proven or suspected coronary artery disease by coronary arteriography, nor is it feasible to examine groups of patients at regular intervals by this technique. Coronary arteriographic data are only available for selected groups of patients and in the vast majority of patients only one examination, reflecting the anatomical changes at one point in time, is available. It may even be doubted if prognostic stratification would be significantly more accurate if sequential arteriograms were available because progression studies using multiple sequential coronary arteriograms have shown that progression of coronary atherosclerosis occurs in a largely unpredictable manner and in bouts rather than as a continuous process1'1.
study period underwent no mechanical revascularization procedure and who did not receive intensive pharmacological treatment in the context of a research protocol'. This implies that what we call 'natural history' is in fact the clinical course in patients who receive the medical therapy generally given in the period of follow-up. Thus, when medical strategies change, the natural history changes accordingly. Consequently, natural history studies may no longer represent the current situation when they are finished. This, however, is an unavoidable shortcoming of almost all follow-up studies, especially of long-term follow-up studies, irrespective of study design and it affects studies concerning therapeutic interventions in the same manner as it does natural history studies.
Natural history of CAD 71
The natural history of moderately severe coronary artery disease THE PROGNOSTIC VALUE OF THE CORONARY ARTERIOGRAM
Traditionally, the severity of coronary artery disease has been divided into one-, two-, and three-vessel disease and left main coronary artery disease. Several other arteriographic scoring systems have also been used but none of these has gained much popularity. The limitations of a prognostic stratification primarily based upon the number of vessels > 50% or > 70% narrowed have been
recognized since its introduction1131. However, it has the advantage of simplicity and it has become a practical standard for comparison of different studies. Generally one- and two-vessel involvement is considered mild or moderately severe while three-vessel involvement and left main coronary artery disease (the latter irrespective of associated lesions) are considered severe. In view of the generally recognized poor prognosis of medically treated patients with left main or triple vessel disease which disqualifies them from piloting, we will restrict this discussion to the groups with a relatively favourable prognosis, that is patients with single-vessel or two-vessel involvement. Single-vessel involvement In all studies single-vessel involvement has a relatively benign prognosis. In the Cleveland Clinic studies which comprised mainly patients who underwent coronary arteriography before coronary artery bypass surgery had become a therapeutic option for a significant proportion of patients, 5-year survival in patients with single-vessel disease was 83% while 5-year survival in the entire group of patients with coronary artery disease (CAD) was 64%'2'. However, after 4 to 5 years the mortality rate increased, resulting in 10- and 15-year survival rates of 62% and 48% respectively116'. The increasing mortality in patients with single-vessel involvement may be explained by progression to multiple-vessel involvement in a number of cases. However, with time, increasing mortality from non-cardiac causes also plays a role. A later study from the same institution selected patients who had mild angina or myocardial infarction without angina'171. In this group 5-year survival in patients with single-vessel involvement was 94-5%. The improved survival, as compared to the previous series, may be explained by the selection criteria, but improvements in medical therapy have also reduced mortality. Using CASS registry data (including randomized and non-randomized patients) Mock et a/.'181 found a 4-year survival of medically treated patients with single-vessel involvement of 92%, while in a European population Gohlke et al.[i9] found a 6-year survival rate of 88%. The best prognosis of patients with single-vessel involvement was reported by Hueb et alP°] who observed no mortality in a 2- to 8-year follow-up. Patients with single-vessel disease can further be stratified according to the location of disease. Obstruction of the left anterior descending artery, particularly in its proximal portion, has the highest mortality which approximates that of two-vessel disease, while right coronary artery involvement has the best prognosis'161. It has been postulated that occlusion has a better prognosis than less than total obstruction because in the former there is a relatively stable situation. This, however, appears not to be the case. Overall there is no strong correlation between severity of narrowing and survival, but various studies indicate a somewhat elevated mortality in patients with occlusion. In this context subtotal narrowing deserves particular attention. It has been demonstrated in patients who underwent percutaneous
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
of the United States for the same mean age1'2'. Yet, of their patients more than 90% had chest pain which was classified in 10% as typical angina pectoris. In addition, a substantial number of patients had an abnormal baseline ECG*412'. Papanicolaou et a/.1'3' found a myocardial infarction-free survival rate of 99% at 5 years for patients with entirely normal coronary arteries. Kemp et a/.1'41 analysed patients included in the registry of the Coronary Artery Surgery Study (CASS). There were 3136 patients with an entirely normal arteriogram and in this group the 7-year survival rate was 96%. Interestingly, the electrocardiographic response to exercise at stress testing appeared to have no predictive value. These studies indicate that patients with normal coronary arteriograms and normal left ventricular angiograms have a good to excellent prognosis irrespective of the clinical picture. If it is true that a significant proportion of these patients has changes of the small coronary branches then this must be a benign condition. Even in patients with coronary artery spasm, a low mortality and morbidity has been observed if the coronary arteriogram shows no significant obstruction"51. If mild coronary atherosclerosis, generally defined as causing
The natural history of angiographically demonstrated coronary artery disease A. V. G. BRUSCHKE, E. E. VAN DER WALL AND V. MANGER CATS
University Hospital, Leiden, The Netherlands KEY WORDS: Aircrew licensing, aviation, natural history, coronary artery.
Introduction
In spite of these limitations, the first large studies that appeared in the literature of the early 1970s (about 15 years after Sones had introduced the technique of selective coronary arteriography) showed surprisingly good correlations between angiographic findings and clinical followup data'2"51. At that time coronary bypass surgery had just started, catheter interventions had still to be developed, and medical management of myocardial infarction and left ventricular failure was not nearly as effective as it is today. Currently, mechanical and pharmacological interventions are common practice in patients with coronary artery disease and interfere with the 'natural history'. Indeed, as Proudfit wrote: 'It is the function of the physician to make the history as desirably unnatural as possible'161. Admitting that it is neither feasible nor ethical to study the true natural history of coronary atherosclerosis we will for practical purposes redefine natural history as 'the clinical evolution in patients who before or during the Correspondrncc: A. V. G. Bruschke, University Hospital, Department of Cardiology, Building I, C5-P, Postbus 9600, 2300 RC Leiden, The Netherlands. 0I95-668X 92 OH0070 + 06S08.00-0
Prognostic significance of a normal or slightly to moderately abnormal coronary arteriogram To assess the true prognostic value of the coronary arteriogram, patients with cardiac abnormalities other than coronary artery disease should be excluded. This may be difficult to achieve. It is in particular difficult to exclude changes of the microcirculation if the coronary arteriogram does not show haemodynamically significant obstructions. Coronary arteriography under optimal conditions allows visualization of vessels with diameters down to about 0-5 mm, but in practice it is often impossible to demonstrate changes in vessels with diameters less than 1 mm'71. It has been postulated that a substantial proportion of patients undergoing coronary arteriography for angina pectoris or angina-like symptoms and whose coronary arteriograms appear to be free of atherosclerotic changes in fact have obstructions in the small coronary vessels as may be inferred from a reduced coronary flow reserve18"'01. Small vessel coronary artery disease has been clearly demonstrated to occur in a variety of diseases'"1, however, it is uncertain if it is present in a significant proportion of the patients who have symptoms or other evidence suggesting coronary artery disease in association with a normal coronary arteriogram. Proudfit el al. found in a follow-up study that patients with normal coronary arteriograms or minimal disease had a 10-year survival from coronary disease of 99-2%, which was better than survival for the general population © 1992 The European Society of Cardiology
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
Coronary arteriography is still the only diagnostic method which allows accurate assessment of the anatomical changes caused by coronary atherosclerosis. Therefore it seems logical to base studies on the natural history of coronary atherosclerosis on findings at coronary arteriography. However, this approach is also subject to considerable, and to a certain extent insurmountable, problems. It is not feasible to study entire populations or large groups of sequential patients with proven or suspected coronary artery disease by coronary arteriography, nor is it feasible to examine groups of patients at regular intervals by this technique. Coronary arteriographic data are only available for selected groups of patients and in the vast majority of patients only one examination, reflecting the anatomical changes at one point in time, is available. It may even be doubted if prognostic stratification would be significantly more accurate if sequential arteriograms were available because progression studies using multiple sequential coronary arteriograms have shown that progression of coronary atherosclerosis occurs in a largely unpredictable manner and in bouts rather than as a continuous process1'1.
study period underwent no mechanical revascularization procedure and who did not receive intensive pharmacological treatment in the context of a research protocol'. This implies that what we call 'natural history' is in fact the clinical course in patients who receive the medical therapy generally given in the period of follow-up. Thus, when medical strategies change, the natural history changes accordingly. Consequently, natural history studies may no longer represent the current situation when they are finished. This, however, is an unavoidable shortcoming of almost all follow-up studies, especially of long-term follow-up studies, irrespective of study design and it affects studies concerning therapeutic interventions in the same manner as it does natural history studies.
Natural history of CAD 71
The natural history of moderately severe coronary artery disease THE PROGNOSTIC VALUE OF THE CORONARY ARTERIOGRAM
Traditionally, the severity of coronary artery disease has been divided into one-, two-, and three-vessel disease and left main coronary artery disease. Several other arteriographic scoring systems have also been used but none of these has gained much popularity. The limitations of a prognostic stratification primarily based upon the number of vessels > 50% or > 70% narrowed have been
recognized since its introduction1131. However, it has the advantage of simplicity and it has become a practical standard for comparison of different studies. Generally one- and two-vessel involvement is considered mild or moderately severe while three-vessel involvement and left main coronary artery disease (the latter irrespective of associated lesions) are considered severe. In view of the generally recognized poor prognosis of medically treated patients with left main or triple vessel disease which disqualifies them from piloting, we will restrict this discussion to the groups with a relatively favourable prognosis, that is patients with single-vessel or two-vessel involvement. Single-vessel involvement In all studies single-vessel involvement has a relatively benign prognosis. In the Cleveland Clinic studies which comprised mainly patients who underwent coronary arteriography before coronary artery bypass surgery had become a therapeutic option for a significant proportion of patients, 5-year survival in patients with single-vessel disease was 83% while 5-year survival in the entire group of patients with coronary artery disease (CAD) was 64%'2'. However, after 4 to 5 years the mortality rate increased, resulting in 10- and 15-year survival rates of 62% and 48% respectively116'. The increasing mortality in patients with single-vessel involvement may be explained by progression to multiple-vessel involvement in a number of cases. However, with time, increasing mortality from non-cardiac causes also plays a role. A later study from the same institution selected patients who had mild angina or myocardial infarction without angina'171. In this group 5-year survival in patients with single-vessel involvement was 94-5%. The improved survival, as compared to the previous series, may be explained by the selection criteria, but improvements in medical therapy have also reduced mortality. Using CASS registry data (including randomized and non-randomized patients) Mock et a/.'181 found a 4-year survival of medically treated patients with single-vessel involvement of 92%, while in a European population Gohlke et al.[i9] found a 6-year survival rate of 88%. The best prognosis of patients with single-vessel involvement was reported by Hueb et alP°] who observed no mortality in a 2- to 8-year follow-up. Patients with single-vessel disease can further be stratified according to the location of disease. Obstruction of the left anterior descending artery, particularly in its proximal portion, has the highest mortality which approximates that of two-vessel disease, while right coronary artery involvement has the best prognosis'161. It has been postulated that occlusion has a better prognosis than less than total obstruction because in the former there is a relatively stable situation. This, however, appears not to be the case. Overall there is no strong correlation between severity of narrowing and survival, but various studies indicate a somewhat elevated mortality in patients with occlusion. In this context subtotal narrowing deserves particular attention. It has been demonstrated in patients who underwent percutaneous
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on March 26, 2016
of the United States for the same mean age1'2'. Yet, of their patients more than 90% had chest pain which was classified in 10% as typical angina pectoris. In addition, a substantial number of patients had an abnormal baseline ECG*412'. Papanicolaou et a/.1'3' found a myocardial infarction-free survival rate of 99% at 5 years for patients with entirely normal coronary arteries. Kemp et a/.1'41 analysed patients included in the registry of the Coronary Artery Surgery Study (CASS). There were 3136 patients with an entirely normal arteriogram and in this group the 7-year survival rate was 96%. Interestingly, the electrocardiographic response to exercise at stress testing appeared to have no predictive value. These studies indicate that patients with normal coronary arteriograms and normal left ventricular angiograms have a good to excellent prognosis irrespective of the clinical picture. If it is true that a significant proportion of these patients has changes of the small coronary branches then this must be a benign condition. Even in patients with coronary artery spasm, a low mortality and morbidity has been observed if the coronary arteriogram shows no significant obstruction"51. If mild coronary atherosclerosis, generally defined as causing
