LVH - A Suitable Case for Treatment Cardiology 1992;81:274-282
Department of Medicine, Clinic and Polyclinic B, University of Düsseldorf, FRG
Left Ventricular Hypertrophy, Myocardial Blood Flow and Coronary Flow Reserve
Key Words
Abstract
Left ventricular hypertrophy Myocardial blood flow Coronary flow reserve
In this review, the coronary haemodynamics of hypertrophic heart disease are discussed with reference to data published over the last 15 years. Coronary reserve is reduced in the pres ence of concentric cardiac hypertrophy, but is similar to nor mal in hypertrophic obstructive cardiomyopathy and aortic stenosis, despite marked left ventricular hypertrophy. A mod erate decrease in coronary reserve is found in aortic incompe tence and in dilated essential hypertension. In hypertensive heart disease, improvement in coronary reserve can be achieved by long-term vasodilator therapy.
Introduction
By definition, cardiac hypertrophy may be: (i) concentric, (ii) eccentric or (iii) irregular (asymmetric). If left ventricular hypertrophy (LVH) is moderate, normal cardiac function may be maintained for a long period. How ever, if cardiac hypertrophy is severe, deterio ration of left ventricular function, left ventric ular dilatation and cardiac failure may result [1,2]. The reason for the transition from con centric to eccentric hypertrophy (or dilata tion) is multifactorial, but is still not fully understood. One of the possible mechanisms underlying the deterioration of left ventricu lar function in developing hypertrophy may
be initiated by impairment of the blood sup ply to the myocardium as a result of involve ment in the coronary artery system due to cor onary artery disease (coronary stenosis), or as a result of widespread narrowing of the coro nary resistance vessels due to chronic pressure overload of the coronary resistance arteries [3-8]. Hypertensive hypertrophy, in contrast to non-hypertensive hypertrophy (e.g. aortic ste nosis, hypertrophic cardiomyopathy), is most regularly associated with an impairment in coronary reserve. The underlying mecha nisms have not yet been clearly identified; however, there is evidence that structural al terations in the coronary resistance vessels
B.E. Straucr Department o f Medicine, Clinic and Polyclinic B University of Düsseldorf Moorcnstrassc 5 D-4000 Düsseldorf (FRG)
©1992 S. Karger AG, Basel 0008-6312/92/ 0815-0274$2.75/0
Downloaded by: Kings's College London 137.73.144.138 - 10/20/2017 10:34:11 PM
BE. St rauer
may play a major role in the pathological increase in coronary resistance in maximum flow conditions. It is the aim of this review to describe coro nary haemodynamics in hypertrophic heart disease and to analyse the influence of the vascular component of coronary resistance on the coronary functional parameters, and the influence of the myocardial component of coronary resistance on coronary reserve and myocardial oxygen consumption. These data are based on studies that were performed over the last 15 years [2, 4, 5].
Coronary Blood Flow and Coronary Reserve Fig. 1 . Coronary reserve in normal subjects (N), in patients with congestive cardiomyopathies (COCM: normal coronary arteriogram), and in patients with coronary artery disease (CAD; left coronary artery >75%).
alytical methods. Systematic analyses of dif ferent coronary blood flow measurements have proved the gas chromatographic argon method to be the most appropriate and accu rate method for clinical conditions. This method has been previously described in de tail [2, 4, 5],
Determinants of Coronary Reserve
In a large group of patients with coronary disease, the resting flow was near normal; however, the coronary reserve was consider ably reduced, by a mean of more than 50% (fig. 1). This reduction in coronary reserve is due to an abnormal increase in the vasal com ponent of coronary vascular resistance (coro nary stenosis).
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Coronary blood flow depends on at least three factors: (i) the vascular resistance of large and small coronary arteries (vascular component of coronary resistance): (ii) the myocardial (i.e. extravascular) component of coronary resistance, and (iii) rheologic prop erties of the blood. Disturbances in coronarycirculation may be detected as alterations in resting or in maximal flow capacity, that is, in coronary reserve. Coronary reserve is defined and deter mined as the ratio of coronary resistance at rest (i.e. under control conditions) and under maximal coronary vasodilatation. The latter can be achieved by various interventions, the most important and clinically relevant exam ple being the intravenous administration of dipyridamole, 0.5 mg/kg body weight. For pa tients without coronary artery disease, the coronary reserve is about 400-500%: that is, the normal heart is capable of reducing its cor onary resistance to minimal values of 0.180.2 mm Hg/ml/min/100 g or to increase coro nary flow approximately four- to five-fold. Determination of coronary reserve in hu mans requires the availability of adequate an-
Fig. 2. Coronary reserve in nor mal subjects (N), in patients with essential hypertension without cor onary stenosis (EH), in patients with essential hypertension with coronary stenosis (EH + CAD), and in patients with normotensive cor onary artery disease (CAD). (Note the considerable reduction already present in patients with essential hypertension and normal coronary results.) LVMM = Left ventricular muscle mass: EDV = end diastolic volume; LCA = left coronary ar tery.
276
Slraucr
Coronary Reserve in Hypertensive Hypertrophy
The coronary reserve of the left ventricle, as determined by pharmacological methods in subjects with hypertension but without cor onary artery disease, remained at 72% of nor mal values, whereas it was reduced to 42% in subjects with hypertension and coronary ar tery' disease (fig. 2). Thus, coronary vascular reserve was similar in essential hypertension with coronary artery disease and in coronary artery disease without essential hypertension: the occurrence of the coronary factor in essen tial hypertension with respect to the coronary vascular reserve seems to indicate that the risk of ischaemia is at least quantitatively comparable to that in normotensive coronary artery disease. It should be pointed out that coronary reserve was considerably reduced in essential hypertension without coronary artery disease, that is, with normal coronary angiographic results. There was no relationship between the decrease in coronary vascular reserve and the end diastolic pressure, or between the end dia
LVH. Myocardial Blood Flow and Coronary Flow Reserve
Downloaded by: Kings's College London 137.73.144.138 - 10/20/2017 10:34:11 PM
Coronary reserve may be reduced not only in coronary disease, but also in abnormal compression of the coronary vascular bed, for example, as a result of ventricular dilatation or increased left ventricular end diastolic pressure [8], These factors are of extravascular origin and are summarised as the myocar dial component of coronary resistance. There fore, coronary reserve is markedly reduced in patients with congestive cardiomyopathy as a consequence of abnormal extracoronary vas cular pressure (fig. 1). In addition to coronary artery disease and myocardial disease, coronary insufficiency and angina pectoris may occur when coronary artériographie values are normal, as a result of disturbances in the coronary microcircula tion. Interference with coronary sinus blood flow occurs due to disturbances of the vascu lar or rheologic component of the small blood vessels that arc not visible on coronary arteri ography. These vessels usually have a diame ter of less than 200 pm. Three major kinds of disturbances in coro nary microcirculation have to be considered: vascular, rheologic and metabolic.
end diastolic and peak systolic wall stress) does not correlate with the impairment in the coronary vascular reserve in essential hyper tension with no abnormal findings on coro nary angiography, it is obvious that this func tional disturbance in coronary regulation may be the result of an effect on the small intramu ral coronary arteries. It is not necessary to assume a functional coronary constriction, since histological examination of the coronary vascular system in arterial hypertension has shown that the small arteries and arterioles may exhibit thickened vascular wall struc tures. fibrosis, sclerosis, and narrowed lumina. In patients with essential hypertension and normal coronary angiographic results, the left ventricle must thus be regarded as being at risk for the development of ischaemia, from the standpoint of the coronary regulatory ca pacity alone.
Structural Vascular Alterations in Hypertensive Hypertrophy
Myocardial biopsies taken from hyperten sive patients with LVH revealed both myo cardial and coronary vascular changes depen dent on the degree of hypertrophy. In the myocardium, an increase in muscle fibre thickness, an increased presence of small scars and an increase in the collagen content were found. The coronary arteries showed all de grees of smooth vascular hypertrophy (fig. 3). Correlation between hypertensives with thickened coronary arteries and coronary re serve demonstrates a significant reduction in coronary reserve parallel to an increase in smooth vascular wall thickness (fig. 4). Thus, in clinical arterial hypertension associated with LVH. this study provides evidence for the existence of medial hypertrophy in hy pertensive heart disease. Moreover, these vas cular structural changes parallel the clinical
277
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stolic volume and wall stress. However, coro nary vascular reserve was found to decrease with increasing peak systolic wall stress, whereas coronary vascular reserve was nor mal when systolic wall stress was normal or reduced, as in hypertrophic obstructive car diomyopathy [1.4, 5]. For high systolic wall stress, the mass-to-volume ratio was generally lower than for low systolic wall stress. No ten dency in any direction could be detected in the relationship between the left ventricular coronary vascular reserve and the degree of hypertrophy, as assessed on the basis of the mass-to-volume ratio. Quantitatively, the impairment in the left ventricular coronary vascular reserve in es sential hypertension with significant coronary stenosis (more than 75% as determined by coronary angiography) is comparable to that in normotensive coronary artery disease with a corresponding degree of stenosis. However, even an equal impairment in coronary reserve results in a presumably higher risk of isch aemia of the left ventricle in essential hyper tensive patients with coronary stenosis than in normotensive coronary artery disease, since the triggering conditions for the devel opment of angina pectoris and coronary in sufficiency (the imbalance between oxygen supply and demand) are considerably en hanced by the increased systolic left ventricu lar pressure load of hypertensive patients. Thus, there is a high risk of ischaemia in essential hypertension with coronary artery disease. As stated previously, even in essential hypertension without coronary stenosis de tectable by coronary angiography, there is marked impairment in the coronary reserve. This cannot be explained by the coronary fac tor, as determined by coronary angiography. Because the myocardial factor (as determined by estimating the degree of LVH. the massto-volume ratio of the left ventricle, and the
Fig. 3. Cross-sections of two arterioles taken as biopsies from 2 patients with hypertensive hyper trophy. Left: almost normal vascu lar structure, coronary reserve was normal. Right: considerable media hypertrophy and adventitial fibro sis, coronary reserve was
Department of Medicine, Clinic and Polyclinic B, University of Düsseldorf, FRG
Left Ventricular Hypertrophy, Myocardial Blood Flow and Coronary Flow Reserve
Key Words
Abstract
Left ventricular hypertrophy Myocardial blood flow Coronary flow reserve
In this review, the coronary haemodynamics of hypertrophic heart disease are discussed with reference to data published over the last 15 years. Coronary reserve is reduced in the pres ence of concentric cardiac hypertrophy, but is similar to nor mal in hypertrophic obstructive cardiomyopathy and aortic stenosis, despite marked left ventricular hypertrophy. A mod erate decrease in coronary reserve is found in aortic incompe tence and in dilated essential hypertension. In hypertensive heart disease, improvement in coronary reserve can be achieved by long-term vasodilator therapy.
Introduction
By definition, cardiac hypertrophy may be: (i) concentric, (ii) eccentric or (iii) irregular (asymmetric). If left ventricular hypertrophy (LVH) is moderate, normal cardiac function may be maintained for a long period. How ever, if cardiac hypertrophy is severe, deterio ration of left ventricular function, left ventric ular dilatation and cardiac failure may result [1,2]. The reason for the transition from con centric to eccentric hypertrophy (or dilata tion) is multifactorial, but is still not fully understood. One of the possible mechanisms underlying the deterioration of left ventricu lar function in developing hypertrophy may
be initiated by impairment of the blood sup ply to the myocardium as a result of involve ment in the coronary artery system due to cor onary artery disease (coronary stenosis), or as a result of widespread narrowing of the coro nary resistance vessels due to chronic pressure overload of the coronary resistance arteries [3-8]. Hypertensive hypertrophy, in contrast to non-hypertensive hypertrophy (e.g. aortic ste nosis, hypertrophic cardiomyopathy), is most regularly associated with an impairment in coronary reserve. The underlying mecha nisms have not yet been clearly identified; however, there is evidence that structural al terations in the coronary resistance vessels
B.E. Straucr Department o f Medicine, Clinic and Polyclinic B University of Düsseldorf Moorcnstrassc 5 D-4000 Düsseldorf (FRG)
©1992 S. Karger AG, Basel 0008-6312/92/ 0815-0274$2.75/0
Downloaded by: Kings's College London 137.73.144.138 - 10/20/2017 10:34:11 PM
BE. St rauer
may play a major role in the pathological increase in coronary resistance in maximum flow conditions. It is the aim of this review to describe coro nary haemodynamics in hypertrophic heart disease and to analyse the influence of the vascular component of coronary resistance on the coronary functional parameters, and the influence of the myocardial component of coronary resistance on coronary reserve and myocardial oxygen consumption. These data are based on studies that were performed over the last 15 years [2, 4, 5].
Coronary Blood Flow and Coronary Reserve Fig. 1 . Coronary reserve in normal subjects (N), in patients with congestive cardiomyopathies (COCM: normal coronary arteriogram), and in patients with coronary artery disease (CAD; left coronary artery >75%).
alytical methods. Systematic analyses of dif ferent coronary blood flow measurements have proved the gas chromatographic argon method to be the most appropriate and accu rate method for clinical conditions. This method has been previously described in de tail [2, 4, 5],
Determinants of Coronary Reserve
In a large group of patients with coronary disease, the resting flow was near normal; however, the coronary reserve was consider ably reduced, by a mean of more than 50% (fig. 1). This reduction in coronary reserve is due to an abnormal increase in the vasal com ponent of coronary vascular resistance (coro nary stenosis).
275
Downloaded by: Kings's College London 137.73.144.138 - 10/20/2017 10:34:11 PM
Coronary blood flow depends on at least three factors: (i) the vascular resistance of large and small coronary arteries (vascular component of coronary resistance): (ii) the myocardial (i.e. extravascular) component of coronary resistance, and (iii) rheologic prop erties of the blood. Disturbances in coronarycirculation may be detected as alterations in resting or in maximal flow capacity, that is, in coronary reserve. Coronary reserve is defined and deter mined as the ratio of coronary resistance at rest (i.e. under control conditions) and under maximal coronary vasodilatation. The latter can be achieved by various interventions, the most important and clinically relevant exam ple being the intravenous administration of dipyridamole, 0.5 mg/kg body weight. For pa tients without coronary artery disease, the coronary reserve is about 400-500%: that is, the normal heart is capable of reducing its cor onary resistance to minimal values of 0.180.2 mm Hg/ml/min/100 g or to increase coro nary flow approximately four- to five-fold. Determination of coronary reserve in hu mans requires the availability of adequate an-
Fig. 2. Coronary reserve in nor mal subjects (N), in patients with essential hypertension without cor onary stenosis (EH), in patients with essential hypertension with coronary stenosis (EH + CAD), and in patients with normotensive cor onary artery disease (CAD). (Note the considerable reduction already present in patients with essential hypertension and normal coronary results.) LVMM = Left ventricular muscle mass: EDV = end diastolic volume; LCA = left coronary ar tery.
276
Slraucr
Coronary Reserve in Hypertensive Hypertrophy
The coronary reserve of the left ventricle, as determined by pharmacological methods in subjects with hypertension but without cor onary artery disease, remained at 72% of nor mal values, whereas it was reduced to 42% in subjects with hypertension and coronary ar tery' disease (fig. 2). Thus, coronary vascular reserve was similar in essential hypertension with coronary artery disease and in coronary artery disease without essential hypertension: the occurrence of the coronary factor in essen tial hypertension with respect to the coronary vascular reserve seems to indicate that the risk of ischaemia is at least quantitatively comparable to that in normotensive coronary artery disease. It should be pointed out that coronary reserve was considerably reduced in essential hypertension without coronary artery disease, that is, with normal coronary angiographic results. There was no relationship between the decrease in coronary vascular reserve and the end diastolic pressure, or between the end dia
LVH. Myocardial Blood Flow and Coronary Flow Reserve
Downloaded by: Kings's College London 137.73.144.138 - 10/20/2017 10:34:11 PM
Coronary reserve may be reduced not only in coronary disease, but also in abnormal compression of the coronary vascular bed, for example, as a result of ventricular dilatation or increased left ventricular end diastolic pressure [8], These factors are of extravascular origin and are summarised as the myocar dial component of coronary resistance. There fore, coronary reserve is markedly reduced in patients with congestive cardiomyopathy as a consequence of abnormal extracoronary vas cular pressure (fig. 1). In addition to coronary artery disease and myocardial disease, coronary insufficiency and angina pectoris may occur when coronary artériographie values are normal, as a result of disturbances in the coronary microcircula tion. Interference with coronary sinus blood flow occurs due to disturbances of the vascu lar or rheologic component of the small blood vessels that arc not visible on coronary arteri ography. These vessels usually have a diame ter of less than 200 pm. Three major kinds of disturbances in coro nary microcirculation have to be considered: vascular, rheologic and metabolic.
end diastolic and peak systolic wall stress) does not correlate with the impairment in the coronary vascular reserve in essential hyper tension with no abnormal findings on coro nary angiography, it is obvious that this func tional disturbance in coronary regulation may be the result of an effect on the small intramu ral coronary arteries. It is not necessary to assume a functional coronary constriction, since histological examination of the coronary vascular system in arterial hypertension has shown that the small arteries and arterioles may exhibit thickened vascular wall struc tures. fibrosis, sclerosis, and narrowed lumina. In patients with essential hypertension and normal coronary angiographic results, the left ventricle must thus be regarded as being at risk for the development of ischaemia, from the standpoint of the coronary regulatory ca pacity alone.
Structural Vascular Alterations in Hypertensive Hypertrophy
Myocardial biopsies taken from hyperten sive patients with LVH revealed both myo cardial and coronary vascular changes depen dent on the degree of hypertrophy. In the myocardium, an increase in muscle fibre thickness, an increased presence of small scars and an increase in the collagen content were found. The coronary arteries showed all de grees of smooth vascular hypertrophy (fig. 3). Correlation between hypertensives with thickened coronary arteries and coronary re serve demonstrates a significant reduction in coronary reserve parallel to an increase in smooth vascular wall thickness (fig. 4). Thus, in clinical arterial hypertension associated with LVH. this study provides evidence for the existence of medial hypertrophy in hy pertensive heart disease. Moreover, these vas cular structural changes parallel the clinical
277
Downloaded by: Kings's College London 137.73.144.138 - 10/20/2017 10:34:11 PM
stolic volume and wall stress. However, coro nary vascular reserve was found to decrease with increasing peak systolic wall stress, whereas coronary vascular reserve was nor mal when systolic wall stress was normal or reduced, as in hypertrophic obstructive car diomyopathy [1.4, 5]. For high systolic wall stress, the mass-to-volume ratio was generally lower than for low systolic wall stress. No ten dency in any direction could be detected in the relationship between the left ventricular coronary vascular reserve and the degree of hypertrophy, as assessed on the basis of the mass-to-volume ratio. Quantitatively, the impairment in the left ventricular coronary vascular reserve in es sential hypertension with significant coronary stenosis (more than 75% as determined by coronary angiography) is comparable to that in normotensive coronary artery disease with a corresponding degree of stenosis. However, even an equal impairment in coronary reserve results in a presumably higher risk of isch aemia of the left ventricle in essential hyper tensive patients with coronary stenosis than in normotensive coronary artery disease, since the triggering conditions for the devel opment of angina pectoris and coronary in sufficiency (the imbalance between oxygen supply and demand) are considerably en hanced by the increased systolic left ventricu lar pressure load of hypertensive patients. Thus, there is a high risk of ischaemia in essential hypertension with coronary artery disease. As stated previously, even in essential hypertension without coronary stenosis de tectable by coronary angiography, there is marked impairment in the coronary reserve. This cannot be explained by the coronary fac tor, as determined by coronary angiography. Because the myocardial factor (as determined by estimating the degree of LVH. the massto-volume ratio of the left ventricle, and the
Fig. 3. Cross-sections of two arterioles taken as biopsies from 2 patients with hypertensive hyper trophy. Left: almost normal vascu lar structure, coronary reserve was normal. Right: considerable media hypertrophy and adventitial fibro sis, coronary reserve was
