Angiotensin-converting enzyme inhibition and vascular remodeling in coronary artery disease

New insights from basic laboratory studies and clinical trials have raised the intriguing possibility that the renin-angiotensin-kinin system may play a critical part in the pathophysiology of atherosclerosis. These studies suggest the possibility of an important new therapeutic role for ACE inhibitors: reduction in the risk of atherosclerosis and the complications of coronary artery disease. Ongoing large-scale trials will establish whether the findings from basic laboratory studies and clinical heart failure trials will apply to patients with ischemic heart disease irrespective of the presence or absence of left ventricular dysfunction.     

Effect of coronary artery reperfusion on transmural myocardial remodeling in dogs

BACKGROUND: The effects of reperfusion after coronary occlusion on transmural remodeling of the ischemic region early and late after nontransmural infarction must importantly affect the recovery of regional function. Accordingly, analysis of local volume and three-dimensional strain was performed using a finite element method to determine regional remodeling. Systolic and remodeling strains were measured using radiographic imaging of three columns (approximately 1 cm apart) of four to six gold beads implanted across the left ventricular posterior wall in 6 dogs. METHODS AND RESULTS: After a control study, infarction was produced by 2 to 4 hours of proximal left circumflex coronary artery occlusion followed by reperfusion. Follow-up studies were performed at 2 days, 3 weeks, and 12 weeks with the dogs under anesthesia and in closed-chest conditions. Biplane cineradiography was performed to obtain the three-dimensional coordinates of the beads. At 2 days, end-systolic strains were akinetic with loss of normal transmural gradients of shortening and thickening. Remodeling strains (RS) were determined by use of a nonhomogeneous finite element method by referring the end-diastolic configuration during follow-up studies to its control state at matched end-diastolic pressures and heart rates. Tissue volume at 2 days increased substantially, more at the endocardium (30 +/- 7%) than at the epicardium (5 +/- 12%, P < .01); the increase was associated with an average RS in the wall-thickening direction of 0.18 +/- 0.15 (P < .01) with all other RS near zero. At 12 weeks systolic function partially recovered, with normal wall thickening in the epicardium (radial strain, 0.081 +/- 0.056 [control] versus 0.113 +/- 0.088 [12 weeks]) but with dysfunction in the endocardium (0.245 +/- 0.108 [control] versus 0.111 +/- 0.074 [P < .01] [12 weeks]). This inability of the inner wall to recover function may be related to increased transmural torsional shear and negative longitudinal-radial transverse shear in the inner wall. Volume loss occurred at 12 weeks in the endocardium (-36 +/- 16%) corresponding to transmural gradients in longitudinal RS and both transverse shear RS. Negative longitudinal RS was greater at the endocardium (-0.20 +/- 0.10) than at the epicardium (-0.06 +/- 0.05, P < .01). CONCLUSIONS: These results indicate the presence of marked subendocardial edema 2 days after reperfusion following 2 to 4 hours of coronary occlusion. At 3 months after reperfusion, however, there was volume loss in the inner wall due to shrinkage along the myofiber direction with reduced transmural function and loss of longitudinal shortening, while both tissue volume and function recovered completely in the outer wall.     

Plasma insulin levels in coronary artery disease

Seventy two consecutive patients without a history of diabetes and normal fasting plasma glucose were included in this study of insulin levels. Standard oral glucose tolerance test with 75 gm glucose and fasting and two hour insulin levels were estimated in all patients. Coronary artery disease (CAD) was confirmed or excluded by selective coronary arteriography. In 20 patients, CAD was diagnosed by electrocardiographic (ECG) and clinical evidence of earlier myocardial infarction. Mean fasting plasma insulin was 31.40 +/- 22.2 IU/dl in the CAD positive and 32.3 +/- 13.6 IU/dl in the CAD negative group. The mean two hour plasma insulin was 274.6 +/- 301.1 IU/dl in the CAD positive and 104.8 +/- 74.9 IU/dl in the CAD negative group (p < 0.04). Two hour plasma insulin levels were significantly higher in patients with atherosclerotic coronary artery disease. It is concluded that the estimation of a two hour plasma insulin level after 75 gm of glucose load, could help differentiate CAD from normals.     

Heart rate variability in coronary artery disease

Heart rate variability (HRV) reflects the modulation of cardiac function by autonomic and other physiological systems, and its measurement from ambulatory electrocardiograph (ECG) recordings is a useful method for both clinical and scientific purposes. Heart rate variability can be measured by several linear and non-linear methods, and various methods can give different information on neural and other physiological influences on the heart. Heart rate variability is abnormal in various settings of ischaemic heart disease, and the most important current application of HRV analysis in clinical cardiology is its measurement in postinfarction patients, in whom abnormal HRV indicates an increased risk of cardiac mortality. Future research may expand the clinical utility of HRV measurement to other clinical situations.     

Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.     

Evaluation of coronary artery disease in women

Sepsis syndrome and septic shock remain significant causes of morbidity and mortality. To date, clinical trials of novel agents to treat sepsis have failed to demonstrate clinical efficacy despite considerable animal data to suggest a positive therapeutic benefit. This article reviews the recent major clinical trials on sepsis and discusses the hypotheses on which these therapies are based and the critical issues associated with clinical sepsis. Recommendations for future clinical trials on sepsis are made.     

Left coronary artery transit time in latent coronary heart disease

In a group of 104 cases with possible silent coronary heart disease, 36 had normal angiographic findings and 68 significant coronary artery disease. The transit time of the contrast medium in the left coronary artery was significantly shorter in cases with abnormalities of the artery than in non-afflicted cases. The extent of arterial disease seemed to influence the transit time inversely, whereas the location of the abnormalities did not influence the transit time.     

Psychologic adjustment to coronary artery disease

As improvements in therapy have extended the survival rate of patients with ischemic heart disease, increasing attention to the quality of survival has resulted in an appreciation of the profound effect of psychologic factors on the patient's life. A multidisciplinary approach, including evaluation and management of pertient psychologic factors, should be part of the treatment of all patients with coronary heart disease. Ischemic heart disease often requires both patient and family to make difficult changes in personality and life-style. As soon as the physiologic stress begins to subside, the physician should begin to provide sympathetic, specific guidelines toward acceptance of the disease and accommodation to its limits. Potential problems and their management are discussed within the framework of the three stages of chronic illness.     

Retrograde coronary artery flow in aortic valve disease

Retrograde coronary artery flow was observed angiographically in 43 patients with aortic stenosis and/or regurgitation. In the 24 patients with pure or predominant aortic stenosis, retrograde flow was seen in all 24 during end-systole. In the eight patients with pure aortic regurgitation, retrograde flow was seen mainly during end-diastole (6/8). Among the 11 patients with stenosis and regurgitation, retrograde flow was both end-systolic and enddiastolic. Dominant left coronary arteries were seen in 13 patients; 13 showed retrograde flow in the dominant arteries. Dominant right coronary arteries were seen in 25 patients: all 25 showed retrograde flow equally in the right and left coronary. Five of the 43 patients could not be evaluated for dominance because of coronary artery occlusions. The severity of retrograde flow did not correlate with usual clinical, hemodynamic or tension-stress parameters: angina, electrocardiographic abnormality, end-diastolic pressure or volume, end-systolic pressure or volume, ejection fraction, severity of aortic regurgitation, peak or mean valve gradient, aortic valve area, myocardial tension and stress calculations, or DPTI:SPTI. In summary, retrograde coronary artery flow was seen in all 43 patients with severe aortic valve disease. The time in the cardiac cycle when retrograde flow occurred was related to the type of valve disease. Retrograde flow was seen mainly in the coronary arteries supplying the left ventricle and may result from increased regional myocardial stresses.     

Transmyocardial laser revascularization in allograft coronary artery disease

We used transmyocardial laser revascularization to treat accelerated cardiac allograft atherosclerosis in 2 patients. One patient received transmyocardial laser revascularization as sole therapy, the other as an adjunct to coronary artery bypass grafting. The systolic function improved in both patients, although the patient who had adjunctive transmyocardial laser revascularization died of systemic infection and renal failure on postoperative day 55. The second patient is alive and well 1 1/2 years after the laser procedure. We discuss 4 other patients who received transmyocardial laser revascularization treatment elsewhere in the United States. Transmyocardial laser revascularization has the potential to become important in the treatment of transplant atherosclerosis. Randomized clinical trials are warranted to assess the efficacy of transmyocardial laser revascularization in this setting.     

Ventricular remodeling. Mechanisms and prevention

The changes that take place in the structure and form of the left ventricle have become closely related to increase in clinical events in patients with heart failure. These changes are included in the term remodeling and occur as a response to the initial loss of left ventricular muscle mass. The mechanisms that initiate and maintain this remodeling process have become of great importance since a variety of effective pharmacologic agents have become available. A more complete understanding of remodeling has the potential of preventing the progression of heart failure. This article considers the various aspects of left ventricular remodeling including the cardiomyocytes, the myocardial interstitium, the importance that apoptosis plays the remodeling process.