[Mono- and bi-dimensional echocardiographic parameters in the assessment of left ventricular structure and function: normal values and evaluation of hypertensive heart disease].
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Adult↗
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Relation of arterial structure and function to left ventricular geometric patterns in hypertensive adults.
OBJECTIVES: The present study sought to determine whether conduit artery structure and function vary according to the pattern of left ventricular adaptation to hypertension. BACKGROUND: Although left ventricular geometric pattern has been shown to predict cardiovascular events in hypertension, the arterial status in patients with the different patterns is unknown. METHODS: We evaluated arterial structure and function by carotid ultrasound and applanation tonometry in 271 unmedicated hypertensive patients classified by echocardiography as having normal ventricular geometry (n = 176), concentric remodeling (n = 54), concentric hypertrophy (n = 16) or eccentric hypertrophy (n = 25). RESULTS: All groups were similar in age, gender distribution and body size. Patients with concentric and eccentric hypertrophy had similar blood pressures (mean 173/100 and 171/99 mm Hg, respectively) and left ventricular mass, but compared with patients with normal left ventricular geometry and concentric remodeling, only those with concentric hypertrophy had increased arterial wall thickness (0.96 +/- 0.20 vs. 0.80 +/- 0.18 mm, p < 0.05), end-diastolic diameter (6.38 +/- 0.97 vs. 5.76 +/- 0.87 mm, p < 0.05), cross-sectional area (22.1 +/- 5.71 vs. 16.6 +/- 5.4 mm(1)2 p < 0.05) and elastic modulus (713 +/- 265 vs. 471 +/- 241 dynes/cm2 x 10(-5), p < 0.05). Patients with concentric remodeling and eccentric hypertrophy had similar values for these measures (0.85 +/- 0.22 and 0.89 +/- 0.21 mm, 5.67 +/- 0.77 and 6.04 +/- 0.44 mm, 17.2 +/- 5.4 and 19.7 +/- 5.9 mm2, 558 +/- 263 and 614 +/- 257 dynes/cm2 x 10(-6), respectively), despite lower systolic blood pressures in the former group (156/94 mm Hg, p < 0.001). The prevalence of plaque was comparable in patients with concentric (56%) and eccentric (42%) hypertrophy and significantly greater than that in patients [corrected] with normal geometry (21%). CONCLUSIONS: Among patients with generally mild, uncomplicated systemic hypertension, arterial structure and function are most abnormal when concentric left ventricular hypertrophy is present and may contribute to the more adverse outcome associated with this geometric pattern.
Adaptation, Physiological↗
Left ventricular structure and diastolic function in subjects with two hypertensive parents.
PURPOSE: To examine the influence of (i) strong predisposition to essential hypertension and (ii) insulin sensitivity and plasma levels of cardiomyotrophic hormones on echocardiographic parameters of left ventricular structure and function. METHODS: 26 normotensive subjects (age 18-35) with bi-parental hypertension and 26 matched controls with normotensive parents. Families with non-insulin-dependent diabetes or morbid obesity were excluded. (i) Echocardiography; (ii) plasma concentrations of renin, angiotensin-II, aldosterone, epinephrine and norepinephrine; (iii) euglycaemic, hyperinsulinemic clamp study. RESULTS (means +/- SD): Hypertension-prone subjects vs controls had (i) higher resting systolic (117.0 +/- 14.0 vs 107.1 +/- 11.9 mmHg), and 24-h diastolic blood pressure (77.9 +/- 7.1 vs 72.9 +/- 7.2 mmHg), (ii) higher relative wall thickness (RWT) (0.39 +/- 0.09 vs 0.34 +/- 0.06). They had similar left vetricular mass index, diastolic function parameters, insulin sensitivity and plasma concentrations of cardiomyotrophic hormones. The increased RWT was not attributable to any other factor than the systolic blood pressure. CONCLUSION: In a carefully selected group of subjects with two hypertensive parents compared to a control group, the only echocardiographic change demonstrated was an increased RWT. This remodelling was attributable to a higher systolic blood pressure in the hypertension-prone subjects, but not to insulin sensitivity or a selection of cardiomyotrophic hormones.
Adolescent↗
[Left ventricular myocardial structure and function in patients with primary aldosteronism].
AIM: To study severity of left ventricular hypertrophy (LVH) and left ventricular function in patients with primary aldosteronism (PA) in comparison with hyperaldosteronemia and preoperative arterial hypertension, to follow the dynamics of these parameters early and late after surgical removal of aldosteroma. MATERIALS AND METHODS: Concentration of aldosterone (AC), plasma renin activity (PRA) were measured in 28 PA patients aged 26-58 years before removal of aldosteroma and 1 month, 1 year and 2-5 years after the surgical treatment. Myocardial status was assessed by echocardiography, Doppler echocardiography. 30 healthy subjects aged 25-55 years served control. RESULTS: All the PA patients showed initial or moderate LVH. Index of left ventricular myocardial mass was influenced at the first regression step by primarily diastolic pressure, at the second step--by basal PRA. The diastolic function was affected. One month after unilateral adrenalectomy PRA level and arterial pressure decreased but regression of LVH was noted only 1 year and later after the surgery. Diastolic function improved 1 year after the operation but without normalization within 2-5-year follow-up. CONCLUSION: The lack of a complete normalization of diastolic function of the left ventricle late after the surgery despite regression of LVH and preoperative correlation of the isometric relaxation time with PRA level may be caused by fibrous changes in the myocardium and by hyperaldosteronemia effects.
Adrenalectomy↗
Left ventricular function and myocardial structure in aortic valve disease before and after surgery.
47 patients with aortic valve disease were studied by left ventricular micromanometry and cineangiography before and 18 months after successful valve replacement. There were 27 patients (17 with aortic stenosis, ten with aortic insufficiency) with moderate hypertrophy (angiographic mass less than 180 g/m2) and 20 patients (ten with aortic stenosis, ten with aortic insufficiency) with severe hypertrophy (angiographic mass greater than or equal to 180 g/m2). In the patients with moderate hypertrophy ejection fraction was slightly although not significantly smaller than in 14 controls. Peak systolic circumferential wall stress was, however, significantly increased. In the patients with severe hypertrophy ejection fraction was significantly decreased although afterload was similar to that in the patients with moderate hypertrophy. This indicated a depressed contractile state in the patients with mass exceeding 180 g/m2. After surgery peak systolic wall stress returned to normal levels in both groups. Among the patients with severe preoperative hypertrophy only the patients with aortic stenosis showed a normal ejection fraction after surgery, whereas in the patients with aortic insufficiency ejection fraction improved but remained depressed compared to the controls. In a second study, comparison of left ventricular function with myocardial structure (endomyocardial biopsies) was carried out in 30 patients with aortic valve disease (group 1: 18 with aortic stenosis, group 2: twelve with aortic insufficiency). Both groups were restudied 18.8 and 17.4 months, respectively, following successful aortic valve replacement. Preoperative biplane ejection fraction (60 and 57%), angiographic mass (183 and 186 g/m2), muscle fibre diameter (31.1 and 30.8 mu), interstitial fibrosis (17.1 and 17.4%) and left ventricular fibrous content (31.0 and 32.2 g/m2) were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Aortic Stenosis, Subvalvular↗
Left ventricular cardiac structure and diastolic function in isolated systolic hypertension in the elderly.
We examined the left ventricular cardiac structure and the diastolic function in patients with isolated systolic hypertension (ISH; SBP > or = 160 mmHg and DBP < 90 mmHg) in the elderly. We studied 17 patients with ISH, 24 age-matched patients with essential hypertension (EHT; DBP > or = 90 mmHg) and 17 normotensive controls (NT; SBP < 140 mmHg and DBP < 90 mmHg). EHT were divided into two groups based on the mean wall thickness (MWT) of the left ventricle. Group 1 patients (EHT-I, n = 12) had a MWT < 10 mm and group 2 patients (EHT-II, n = 12) had a MWT > or = 10 mm. We measured left ventricular end-diastolic dimension (LVDd), end-systolic dimensions (LVDs), left ventricular mass index (LVMi) and left ventricular isovolumic relaxation time (IRT) to assess the left ventricular cardiac structure and the diastolic function by M-mode echocardiography. LVDd was significantly smaller in ISH than in NT, EHT-I and EHT-II (P < 0.01). Relative wall thickness was greatest in ISH because of both the decreased chamber size and the increased left ventricular wall thickness. LVMi in ISH was similar to that in EHT-I, but IRT in ISH was significantly longer than that in EHT-I (P < 0.05). These results suggest that ISH in the elderly shows a left ventricular concentric hypertrophy and a severely impaired diastolic function.
Aged↗
[Intracardiac hemodynamics and myocardial contractile function indices in chronic ischemic heart disease].
Echocardiography was used in the examination of 51 patients with chronic ischemic heart disease (IHD) without accompanying hypertension and congestive circulatory insufficiency. With gradual advancement of the disease, a significant increase in left-ventricular volumes during the systole and diastole was recorded as well as a decrease in the ejection fraction (IF) and velocity of circulatory shortening of the myocardial fibres (Vch) in slight variations of the stroke volume. The IF and Vch were the most characteristic indices for appraising the early manifestations of myocardial contractility disorders. The index of left-ventricular structure functioning intensity (SFI) was used to characterize the functional state of the heart muscle. In patients with a severe course of the disease, SFI was found to be reduced because of an increase in the myocardial mass. The developing damage hypertrophy, however, did not provide for full compensation of left-ventricular function and was attended by a reduction of the indices of contractility and pump function of the heart. This provides the grounds for the assumption that the reduction of SFI in patients with severe IHD is associated with exclusion of part of the myocardium involved in the pathological process from effective functioning.
Adult↗
Hypertension and left ventricular hypertrophy in black vs white heart transplant patients 1 year after surgery.
To evaluate the impact of race on the prevalence of systemic hypertension and its effects on left ventricular function, structure, and allograft survival after cardiac transplantation, 31 heart transplant recipients (7 blacks and 24 whites) were studied at 1 year after surgery. Echocardiographic and hemodynamic evaluation of the allografts was performed in addition to clinical follow-up and estimation of patients' survival. There was no difference in the demographic and clinical data between black and white patients. No differences between black and white cardiac transplant recipients were detected with regard to the prevalence of systemic hypertension, left ventricular hypertrophy, left ventricular function, renal function, or patients' survival. Moreover, racial mismatch did not predispose to allograft rejection. However, black patients had significantly higher resting systolic blood pressure and lower heart rates. We conclude that the race of heart recipients is not a detrimental factor in the early outcome after cardiac transplantation. The long-term cardiovascular consequences of these findings should be explored.
Adult↗
The pathophysiology of idiopathic mitral valve prolapse.
Left ventricular structure, function, and the coronary circulation were studied in a subset of patients with mitral valve leaflet prolapse. This group of 26 patients (21 females, five males, with mean age of 46 years), had the syndrome identified as idiopathic mitral valve prolapse (IMVP), which was characterized by a systolic click-murmur, clinical symptoms that were highly variable in duration and intensity, angiographically-documented mitral prolapse, and no obvious associated systemic or cardiovascular disease. Mitral regurgitation was of moderate degree in four, mild in 14, and absent in eight. The left ventricular (LV) end-diastolic volume index was elevated in ten of 25 (40%), the LV mass index was elevated in six of 17 (35%), but the LV anterior wall thickness was increase in only one of 17. Three major patterns of ventricular contraction were identified: 1) normal in seven; 2) abnormal, usually an inferior deformity and/or anterior asynergy, in eight; and 3) hyperkinetic in 11. Normal resting left ventricular function, assessed as an ejection fraction greater than 55%, was present in 17 of 25 (68%). Selective coronary arteriography was essentially normal in all 25 patients studied. An ischemic ECG response was detected during only one of 12 maximal treadmill exercise tests and in none of ten atrial pacing stress tests (AP). Myocardial lactate extraction did not change significantly during AP in six patients. We conclude that cardiomyopathy does not appear to be a primary cause or an important associated component of the IMVP syndrome. Abnormalities of the coronary circulation or of myocardial metabolism were not demonstrated by available methods. A proposed pathophysiological mechanism to explain the clinical and angiographic findings in IMVP is discussed.
Adult↗
New approaches to screening for vascular and cardiac risk.
Cardiovascular morbid events occur as a consequence of vascular and cardiac disease, which can be identified long before symptoms of organ involvement become apparent. Early detection of abnormalities in the small arteries, especially deficiency of endothelial nitric oxide bioactivity, and of structural changes of remodeling in the left ventricle can identify individuals at risk for morbid events. These individuals should be the target for aggressive lifestyle and pharmacologic interventions known to favorably affect the progression of disease. Techniques are now available for screening of asymptomatic individuals to detect early vascular and cardiac abnormalities likely to lead to progression of disease. Pulse wave analysis provides an assessment of small artery elasticity that appears to correlate with endothelial function. Left ventricular structural alterations can be assessed by ultrasound or by circulating levels of brain natriuretic peptide. The usefulness of these early screening techniques to encourage tailored interventions in susceptible individuals needs to be explored in large-scale trials.
Heart Diseases↗
Prolongation of the QT interval in heart failure occurs at low but not at high heart rates.
Abnormal left ventricular structure and function as in, for example, left ventricular hypertrophy or chronic heart failure, is associated with sudden cardiac death and, when the ejection fraction is depressed, with prolongation of the QT interval. The dependence on heart rate of QT interval prolongation in these conditions, and the relationship of any abnormalities either to deranged autonomic nervous system function or to an adverse prognosis, has not been well studied. We therefore investigated (1) the dependence on heart rate of the QT interval, and (2) the relationship between both QT interval and the QT/heart rate slope and markers of adverse prognosis in these two conditions. The QT interval was measured at rest and during exercise in 34 subjects with heart failure, 16 subjects with left ventricular hypertrophy and 16 age-matched controls with normal left ventricular structure and function. QTc (corrected QT) intervals at rest were significantly longer in heart failure patients (471+/-10 ms) than in controls (421+/-6 ms) or in subjects with hypertrophy (420+/-6 ms) (P<0.05). At peak exercise, despite the attainment of similar heart rates, the QT intervals no longer differed from each other, being 281+/-7 ms for controls, 296+/-11 ms in hypertrophy and 303+/-10 ms in heart failure (no significant difference). The QT/heart rate slope was significantly increased in heart failure [2.3+/-0.1 ms.(beats/min)(-1)] compared with controls [1.55+/-0.06 ms.(beats/min)(-1)] and hypertrophy [1. 66+/-0.1 ms.(beats/min)(-1)] (P<0.001). In left ventricular hypertrophy, despite animal data suggesting that QT interval prolongation should occur, no abnormalities were found in QT intervals at rest or during exercise. The QT/heart rate slope did not relate to any markers for an adverse prognosis, except that of prolongation of QT interval. Long QT intervals were associated principally with impairment of left ventricular systolic function. Our data emphasize the dynamic nature of the QT interval abnormalities found in heart failure.
Analysis of Variance↗
Effects of long-term blood pressure control on left and right ventricular structure and function in hypertensive patients.
The functional and anatomical abnormalities of the right ventricle may occur in hypertensive patients with left ventricular hypertrophy (LVH). The present study was designed to assess the functional and structural changes in both left and right ventricles induced by chronic antihypertensive therapy. Doppler and standard echocardiography were performed in 10 hypertensive patients with LVH before and after 1 year of treatment with captopril alone (5 patients) or captopril plus nifedipine (5 patients). We found that the left ventricular mass index and right ventricular thickness were significantly reduced in all patients when compared with pretreatment values. Furthermore, the Doppler-derived diastolic filling indexes show a significant improvement of both ventricular chambers. Our data suggest that anatomical and functional changes induced by therapy in hypertensive patients are not limited to the left ventricle but also involve the right ventricle.
Blood Pressure↗
Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.
OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.
Age Factors↗
Structural basis for changes in left ventricular function and geometry because of chronic mitral regurgitation and after correction of volume overload.
Left ventricular function and myocyte structure were examined in three groups of dogs: (1) 3 months of mitral regurgitation caused by chordal rupture (n = 7); (2) chronic mitral regurgitation followed by mitral valve replacement and a 3-month recovery period (n = 7), and (3) sham controls (n = 8). The left ventricular end-systolic stiffness constant (Kess) was measured as an index of left ventricular contractile function with stress-strain relationships obtained by cinecatheterization. Isolated myocyte structure and composition were examined with computer-assisted morphometry and nuclear area computed with deoxyribonucleic acid fluorescence. Left ventricular contractile function was significantly depressed with chronic mitral regurgitation compared with control values (Kess, 2.1 +/- 0.1 versus 3.6 +/- 0.2; p < 0.05) and returned to control values with mitral valve replacement (3.8 +/- 0.2). Left ventricular mass significantly increased in both the mitral regurgitation and mitral valve replacement groups compared with control values (121 +/- 10, 120 +/- 5 versus 95 +/- 9 gm, respectively; p < 0.05). Myocyte length increased with mitral regurgitation beyond control values (194 +/- 4 versus 218 +/- 8 microns; p < 0.05) and increased beyond mitral regurgitation values after mitral valve replacement (231 +/- 7 microns; p < 0.05). Myocyte volume with mitral regurgitation increased slightly beyond control values (33.5 +/- 0.7 versus 37.6 +/- 1.3 microns3; p = 0.15) and significantly increased with mitral valve replacement (40.1 +/- 1.2 microns3; p < 0.05). Myocyte myofibril volume significantly declined with mitral regurgitation compared with control values (14.8 +/- 1.5 versus 22.2 +/- 0.7 microns3; p < 0.05) and significantly increased beyond both mitral regurgitation and control values with mitral valve replacement (27.1 +/- 1.1 microns3; p < 0.05). Myocyte nuclear area with mitral regurgitation remained unchanged from control values (1430 +/- 122 versus 1163 +/- 89 microns2) but increased significantly with mitral valve replacement (2209 +/- 250 microns2; p < 0.05). In summary, the left ventricular contractile dysfunction with chronic mitral regurgitation is accompanied by increased myocyte length and reduced myofibril content. In contrast, the left ventricular hypertrophy and improved left ventricular pump function with mitral valve replacement were due to increased myocyte volume and increased contractile protein content.
Animals↗
Effects of candesartan on cardiac and arterial structure and function in hypertensive subjects.
OBJECTIVES: To study the effect of candesartan cilexetil on left ventricular mass index (LVMI), left ventricular systolic and diastolic function, arterial structure and function and blood pressure (BP) in hypertensive patients. DESIGN AND METHODS: Patients (n=35), aged >20 years, with hypertension and average baseline LVMI of 89 g/m2 were treated for 24 weeks with candesartan, 16 mg o.d., following a four-week placebo run-in period. If diastolic BP remained above 95 mmHg, hydrochlorothiazide, 12.5 mg o.d.,was added. Left ventricular structure and function were assessed using transthoracic echocardiography. Arterial function and structure were assessed using pulse wave analysis to calculate augmentation index (AIx) and forearm plethysmography to calculate minimum vascular resistance. BP was measured in the office and by 24-hour ambulatory BP monitoring (ABPM). RESULTS: The mean reduction in LVMI was 4.4 g/m2(p=0.022). Left ventricular systolic function was not significantly altered from baseline, but diastolic function significantly improved: the mean change in diastolic time was 54 ms (p=0.037), in peak velocity filling 6.3 cm/s (p=0.023); E:A ratio improved by 0.08 (p=0.049). The mean reduction in forearm vascular resistance was 15 units at rest (p=0.001) and 1.3 units after limb ischaemia (p=0.006). AIx decreased significantly, with a mean reduction of 9% (p<0.001). Central BP also significantly reduced(systolic blood pressure/diastolic blood pressure 31/20 mmHg; p<0.001). BP was significantly reduced, both in the office (22/16 mmHg; p<0.001) and by 24-hourABPM (18/12 mmHg; p<0.001). CONCLUSIONS: Treatment with candesartan, 16 mg o.d., with or without hydrochlorothiazide, for 24 weeks, significantly reduced left ventricular mass and arterial hypertrophy in patients with hypertension. In parallel, there were significant improvements in left ventricular diastolic function and arterial function.
Adult↗
Effect of long-term intensive endurance training on left ventricular structure and diastolic function in prepubertal children.
In children, the fact that cardiac anatomy and function, particularly during the diastolic phase, can adapt to endurance training is still uncertain. Therefore, this study was undertaken to evaluate the effect of a long-term intensive endurance swimming program on the cardiac structure and function of 10-11 year old children. The population consisted of 9 children who belonged to a local youth swimming team (S) and 11 recruited from a primary school to serve as a control group (C). The swimmers had been training on average 10 to 12 h x wk(-1) for at least 2 years. All the subjects were examined by M-mode, 2-dimensional and pulsed-wave Doppler analyses according to standard procedures recommended by the American Society of Echocardiography. Investigations were carried out at rest with the subjects in a supine position. The results showed that highly trained children exhibited significantly higher left ventricular (LV) internal diameter (S: 41.6+/-1.6, C: 39.0+/-2.2 mm/m(1/3) surface area, p<0.01) and LV mass (S: 68+/-7, C: 59+/-5 g/m2 SA, p<0.01). There were, however, no differences between S and C for chamber wall thickness (posterior wall S: 5.2+/-0.6, C: 5.3+/-0.6 mm/m(1/3) SA; septum S: 5.8+/-0.3, C: 5.8+/-0.4 mm/m(1/3) SA), LV systolic function parameters (ejection fraction S: 77.1+/-0.3, C: 77.7+/-0.4%; shortening fraction S: 38.9+/-3.0, C: 39.7+/-4.1%) and the diastolic function parameters, estimated from LV inflow velocitometry (E wave S: 1.04+/-0.12, C: 1.07+/-0.16 m/s; A wave S: 0.45+/-0.10, C: 0.55+/-0.11 m/s). Finally, transaortic Doppler examinations demonstrated similar resting cardiac output (Qc) between both groups (S: 3.76+/-0.81, C: 3.90+/-0.67 l x min(-1)). However, Qc were obtained with significantly lower heart rates (S: 69+/-7, C: 83+/-14 beat x min(-1), P<0.01) and higher stroke volumes (S: 55.2+/-8.0, C: 47.5+/-8.5 ml, P<0.05) in S when compared to C. Thus, these findings strongly suggest that, as has been shown before in adults, several cardiac adaptations (including resting bradycardia, increased stroke volume and enlarged left ventricular internal dimensions) can occur in prepubertal children as a result of intensive endurance training. However, our results did not demonstrate any effects of such training during prepuberty on both diastolic and systolic functions parameters.
Adaptation, Physiological↗
Left ventricular hypertrophy: dissociation of structural and functional effects by therapy.
The heart is one of the major target organs that becomes secondarily involved with the unrelenting and progressive vascular disease of essential hypertension. As a result of this increasing afterload that is imposed upon the left ventricle, the ventricular chamber adapts structurally and functionally. Structural changes involve an increase in muscle mass that is achieved through left ventricular hypertrophy (in a manner similar to the arteriolar changes demonstrated by increased thickening). Unless antihypertensive therapy is interdicted in this disease process, left ventricular failure will ensue as the major cardiac hemodynamic consequence. Left ventricular hypertrophy is also associated with a risk that is independent of the pressure overload and hemodynamic risk. Although antihypertensive therapy will reduce from the hemodynamic alterations, only recently have epidemiological findings suggested that the independent risk of LVH may be reduced with pharmacological therapy. There are no data available to indicate just which agents may reduce the risk from LVH; but relatively recent studies seem to indicate that while all agents may reduce LVH with prolonged therapy only certain classes of agents will do so independent of their hemodynamic factors. Some of these agents, however, may impair cardiac function if arterial pressure is increased abruptly following therapeutic reduction of cardiac mass. Other agents may preserve normal function--or even may improve function. Among those classes of antihypertensive agents that reduce cardiac mass at least in part due to nonhemodynamic factors, are the angiotensin converting enzyme inhibitors, the calcium antagonists, and most adrenergic inhibitors. Evidence will be presented demonstrating the hemodynamic/structural dissociation of those pharmacological agents that reduce cardiac mass with short-term treatment in spontaneously hypertensive rats with left ventricular hypertrophy. Although centrally active adrenolytic, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists all reduce cardiac mass, their structural and cardiac functional effects differ greatly. Even within the ACE inhibitor group their effects vary--improving, impairing, or not changing the Frank-Starling relationships following reduction in left ventricular mass. We postulate great variability of cardiac intramyocytic penetrance of the pharmacological agents and their local intracellular effects on mitogenesis of the ventricular myocyte. The implications on cardiac function and therapy have vast potential. Therefore, current investigative areas involving new concepts of molecular biology of the cardiac myocyte may provide great promise to the quest of unraveling some of the newly postulated questions: What is the role of ionized intracellular calcium? Do the local renin-angiotensin systems in the cardiac and vascular myocyte participate in the development and regression of hypertrophy?(ABSTRACT TRUNCATED AT 400 WORDS)
Angiotensin-Converting Enzyme Inhibitors↗
Angiotensin-converting enzyme inhibition and the progression of congestive cardiomyopathy. Effects on left ventricular and myocyte structure and function.
BACKGROUND: Clinical trials have demonstrated that angiotensin-converting enzyme inhibition (ACEI) improves survival in patients with long-term left ventricular (LV) dysfunction. However, it remained unclear from these clinical reports whether the beneficial effects of ACEI were due to direct improvements in LV myocardial structure and function. Accordingly, the overall objective of the present study was to examine the direct effects of ACEI on both LV and myocyte structure and function in the setting of cardiomyopathic disease. METHODS AND RESULTS: LV and isolated myocyte function and structure were examined in control dogs (n = 6), in dogs after the development of dilated cardiomyopathy caused by rapid ventricular pacing (RVP, 216 beats per minute, 4 weeks, n = 6), and in dogs with RVP and concomitant ACEI (RVP/ACEI, fosinopril 30 mg/kg BID, n = 6). LV ejection fraction fell with RVP compared with control values (35 +/- 3 versus 73 +/- 2%, P < .05) and was higher with RVP/ACEI compared with RVP values (41 +/- 4%, P = .048). LV end-diastolic volume increased with RVP compared with control values (78 +/- 7 versus 101 +/- 7 cm3, P < .05) and was lower with RVP/ACEI (82 +/- 3 cm3, P < .05). Isolated myocyte length increased with RVP (182 +- 1 versus 149 +/- 1 micron), and the velocity of shortening decreased (36 +/- 1 versus 57 +/- 1 micron/s) compared with control values (P < .05). With RVP/ACEI, myocyte length was reduced (169 +/- 1 micron) and velocity of shortening was increased (45 +/- 1 micron/s) compared with RVP values (P < .05). Myocyte velocity of shortening after beta-adrenergic receptor stimulation with 25 nmol/L isoproterenol was reduced with RVP compared with control values (142 +/- 5 versus 193 +/- 8 micron/s, P < .05) and significantly improved with RVP/ACEI (166 +/- 6 micron/s, P < .05). In the RVP group, beta-adrenergic receptor density fell 26%, and cAMP production with beta-adrenergic receptor stimulation was reduced 48% from control values. RVP/ACEI resulted in a normalization of beta-adrenergic receptor density and cAMP production. LV myosin heavy-chain content when normalized to dry weight of myocardium was unchanged with RVP (149 +/- 11 mg per gram dry weight of myocardium [gdwt]) and RVP/ACEI (150 +/- 4 mg/gdwt) compared with control values (165 +/- 4 mg/gdwt). LV collagen content decreased with RVP compared with control values (7.6 +/- 0.4 versus 9.6 +/- 0.8 mg per gram wet weight of myocardium [gwwt], P < .05) but was increased with RVP/ACEI (14.4 +/- 1.3 mg/gwwt, P < .05). CONCLUSIONS: Concomitant ACEI with chronic tachycardia reduced LV chamber dilation and improved myocyte contractile function and beta-adrenergic responsiveness. Contributory cellular and extracellular mechanisms for the beneficial effects of ACEI in this model of dilated cardiomyopathy included a normalization of beta-adrenergic receptor function and enhanced myocardial collagen support. The results from this study provide evidence that ACEI during the development of cardiomyopathic disease provided beneficial effects on LV myocyte contractile processes and myocardial structure.
Angiotensin-Converting Enzyme Inhibitors↗