Relationships between left ventricular mass, left ventricular work and coronary artery size in aortic regurgitation--possible mechanism of myocardial ischemia

To investigate the relationships between coronary artery size, left ventricular (LV) mass, and LV stroke work in aortic regurgitation (AR), these values were measured in 19 patients with severe AR. Twenty normal subjects and 15 patients with mitral regurgitation (MR) were used as control groups. The coronary area index, i.e., the coronary cross-sectional area divided by body surface area (BSA), was larger in the AR group than in the control groups in all measured sites except for the peripheral left anterior descending coronary artery (LAD) and right coronary artery (RCA). However, the coronary area index divided by the LV mass was significantly smaller in AR and MR patients than in normal subjects. Furthermore, the coronary area index divided by LV stroke work was smaller in AR patients than in MR patients and normal subjects. These results suggest that the coronary blood flow associated with the increased LV mass and stroke work caused by regurgitation was insufficient in patients with severe AR, especially in the area of the LAD. Therefore, the occurrence of myocardial ischemia in patients with severe AR may involve inadequate enlargement of the coronary artery which perfuses the LV, in addition to factors such as decreased coronary perfusion pressure, increased coronary artery resistance and decreased coronary flow reserve.     

Studies of correlation between progression of coronary artery disease, as assessed by coronary arteriography, left ventricular end-diastolic pressure, ejection fraction, and employability

The occupational status of a group of 100 male patients, 35 to 68 years of age, with chronic ischaemic heart disease was studied, and related to the severity and distribution of coronary artery stenosis seen on the arteriograms and to left ventricular function. In this series of patients 31 per cent were working, 31 per cent were recorded as temporarily sick, and 38 per cent as permanently disabled. It appears that while the type of previous occupation and physical activity associated with the job were of importance, there was no correlation between employability on the one hand and severity and distribution of coronary artery disease on the other. 'Blue-collar' workers had a higher rate of unemployment than those in 'white collar' occupations, but this could not be explained by differences in severity of coronary artery disease.     

Relation between the site of origin of ventricular premature complexes and the presence and severity of coronary artery disease

Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) have been determined in over 350 plasma samples from 174 subjects while resting supine (basal sample), standing, or exercising. Although increments in both NE and DBH were found with postural change, the further increase in plasma levels of NE during exertion was not attended by any change in levels of DBH. There was no significant correlation between basal levels of DBH and NE nor was there any correlation in their increments after standing or exercising. DBH activity in plasma of subjects with moderate essential hypertension was not different from that of normotensive subjects. It is concluded that plasma DBH is a poor index of acute sympathetic neuronal activity.     

Cesarean section and left ventricular failure caused by coronary artery disease: anesthetic management

A Caesarean section was performed in a 34-year-old patient experiencing a major left heart failure secondary to an anterior myocardial infarction which occurred four years before. At the end of pregnancy, she developed a mild pulmonary hypertension. Caesarean section was decided to maintain a stable haemodynamic status. For the same reason, general anaesthesia with etomidate was preferred rather than epidural analgesia. Haemodynamic monitoring allowed the adequate management of blood pressure, heart rate, pulmonary blood pressure and arterial oxygen saturation. Postoperative analgesia was obtained with opioids administered epidurally.     

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.     

Combined surgery for coronary artery disease and thoracic aortic disease

Combined surgery in 6 cases who had coronary artery disease and thoracic aortic disease simultaneously was analyzed. Case # 1 had ascending aortic replacement under deep hypothermic circulatory arrest because of iatrogenic aortic dissection caused by aortic clamp during the routine coronary artery bypass grafting (CABG). Case # 2 had DeBakey type II chronic dissection. Case # 3 had type I aortic dissection 4 years after the initial CABG. Both case # 2 and # 3 had ascending aortic replacement under retrograde cerebral perfusion along with CABG. Transverse aortic replacement was performed in case # 4, # 5 and # 6 under selective cerebral perfusion along with CABG. Case # 4 was associated with ascending-transverse aortic aneurysm. Case # 5 had aortitis syndrome complicated with severe coronary ostial stenosis and cervical branch stenosis. Case # 6 also had aortitis syndrome, severe coronary ostial stenosis, heavily calcified ascending-transverse aorta, and mitral and aortic regurgitation. This case had mitral and aortic valve replacement additionally. Case # 2 died of low cardiac output syndrome and multi-organ failure postoperatively. Case # 4 did not recover from profound shock that followed the preoperative acute myocardial infarction. The problems of low cardiac output syndrome caused by long interval of ischemic cardiac arrest, and also the problems of proximal anastomotic site of saphenous vein grafts were discussed.     

Mechanism of impaired left ventricular wall motion in the diabetic heart without coronary artery disease

OBJECTIVE: To elucidate whether impairment of the myocardial free fatty acid (FFA) metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease. RESEARCH DESIGN AND METHODS: We performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum. RESULTS: Nine patients with reduced wall motion documented by left ventriculography (LVG), (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 +/- 0.2, mean +/- SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 +/- 0.2, P < 0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P < 0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients. CONCLUSIONS: Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes.     

Anomalous origin of left coronary artery from pulmonary artery: recovery of left ventricular function after dual coronary repair

OBJECTIVES: We reviewed our institutional experience with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) after dual coronary repair to assess preoperative variables predictive of outcome, the time course for postoperative recovery of cardiac function, the short- and long-term complications and our experience with left ventricular assist devices (LVAD) in these patients. BACKGROUND: Outcome after surgical repair of ALCAPA remains incompletely defined. METHODS: The surgical records and echocardiograms of 42 patients were reviewed. Left ventricular function was assessed by fractional shortening z-score (FSz) and stress-velocity index. RESULTS: The overall survival rate was 86%. All six patients who died were < 1 year old and died within 3 days of the operation. More severe preoperative mitral regurgitation (MR) was associated with increased mortality, but age, body surface area, preoperative FSz and end-diastolic dimension were not. We used an LVAD for 7 of 28 patients who underwent repair for ALCAPA since its introduction at our institution, with a survival of 5 of 7 patients. The degree of MR improved in 62% of patients and remained unchanged in 38%. Complications included supravalvar pulmonary stenosis (16 of 21 patients) and baffle leaks (11 of 21 patients) with the intrapulmonary baffling technique. Supravalvar pulmonary stenosis developed in 1 of 11 patients after direct coronary reimplantation. Left ventricular function became normalized in all 28 patients with follow-up past 1 year, regardless of preoperative FSz. Of 13 patients who underwent serial postoperative echocardiography, the average time to normalization of function was 2 to 7 months. CONCLUSIONS: The degree of preoperative MR was predictive of outcome, whereas the severity of preoperative cardiac dysfunction and ventricular dilation were not. Mild and moderate MR tended to improve without mitral valvuloplasty. Complete recovery from myocardial dysfunction is expected after dual coronary repair of ALCAPA.     

Analysis of left ventricular wall movement during isovolumic relaxation and its relation to coronary artery disease

Left ventricular angiograms of 60 patients with ischaemic heart disease and 10 normal subjects were digitized frame by frame in order to study abnormalities of wall movement during the period of isovolumic relaxation. Plots were made of regional wall movement around the cavity throughout the cardiac cycle. In normal subjects 1-5 to 3-0 mm of symmetrical outward wall movement occurred during isovolumic relaxation, associated with an apparent increase of left ventricular volume of 10 +/- 4 per cent. The corresponding peak velocities of wall movement were 4-3 to 5-7 cm/s, significantly less than those recorded in the same region of the cavity after mitral valve opening. In patients with ischaemic heart disease, the following abnormalities were encountered: (1) Abnormal inward movement, which, in single coronary artery disease, occurred in the area supplied by the affected vessel. (2) Abnormal outward movement of more than 6 mm in non-affected areas which appeared to be a compensatory phenomenon. (3) An abnormal cavity shape change towards a more circular configuration before mitral valve opening. (4) Reduced peak rates of wall movement in affected areas during systole and filling. It is concluded that such inward wall movement during isovolumic relaxation is abnormal and a sign of local ischaemia whose presence has significant effects on overall left ventricular function in both systole and diastole.     

Exertional syncope in a patient with aortic stenosis and right coronary artery disease

A female with advanced aortic valvular stenosis and moderate right coronary artery disease experienced an exertional syncope during 24-h ambulatory electrocardiographic monitoring. A progressive bradycardia with 90-s sinus node arrest (cardio-inhibitory response) and premonitory angina pectoris with significant ST segment changes were demonstrated. Our report supports the concept of a neurocardiogenic (vasovagal) mechanism of exertional syncope in patients with aortic stenosis. The predominant left ventricular inferior-wall myocardial ischaemia in our patient might be an additional stimulus to left ventricular mechanoreceptors, resulting in a profound cardio-inhibitory response.     

Low fat intake and coronary artery disease in a population with higher prevalence of coronary artery disease: the Indian paradox

OBJECTIVE: To determine the association between saturated fat intake and prevalence of coronary artery disease (CAD) and coronary risk factors. DESIGN AND SETTING: Total community cross sectional survey of 20 urban streets out of 196 streets, in the city of Moradabad in north India. SUBJECTS AND METHODS: Adult population between 25 to 64 years inclusive comprised of 1806 subjects (904 men, 902 women) were divided into three groups according to level of saturated fat intake as assessed by 7-day dietary intake records (very low < 7%, low 7 to 10%, high > 10% energy (en) per day). RESULTS: We examined the relationship between CAD risk and levels of % en from fat intake. Low (7 to 10% en/day) and high (> 10% en/day) saturated fat were positively and significantly associated with higher prevalence of CAD. The prevalence of coronary risk factors (hypertension, hypercholesterolemia, obesity and sedentary lifestyle) were significantly higher among subjects with low and high saturated fat intake compared to subjects with very low (< 7%) saturated fat intake. Logistic regression analysis with adjustment for age showed that hypercholesterolemia (OR: men 0.89, women 0.68), hypertension (men 0.92, women 0.56), physical activity (men 0.80, women 0.36), obesity (men 0.82, women 0.88) and smoking (0.70 men) were significant risk factors of CAD. Low and high saturated fat intake were associated with more prestigious occupations, higher and middle income status and better educational levels compared to very low saturated fat intake. CONCLUSIONS: The prevalence of CAD and coronary risk factors was higher in urban Indians with low and high saturated fat intake than those with lower saturated fat intake. These findings suggest that the saturated fat intake should be < 7% en/day for prevention of CAD in Indians.     

Comparison of coronary endothelial dynamics with electrocardiographic and left ventricular contractile responses to stress in the absence of coronary artery disease

Coronary artery endothelial dysfunction has been proposed as a cause of myocardial ischemia and symptoms in patients with angina-like chest pain despite normal coronary angiograms, especially those with ischemic-appearing ST-segment depression during exercise (syndrome X). We measured coronary vasomotor responses to acetylcholine (3 to 300 microg/min) in 42 patients (27 women and 15 men) with effort chest pain and normal coronary angiograms who also had normal electrocardiograms and echocardiograms at rest. All patients underwent treadmill exercise testing and measurement of systolic wall thickening responses to dobutamine (40 microg/kg/min) during transesophageal echocardiography. There were no differences in the acetylcholine-stimulated epicardial coronary diameter (+5+/-13% vs +1+/-13%, p=0.386) and flow (+179+/-90% vs +169+/-96%, p=0.756), or in the systolic wall thickening responses (+134+/-65% vs +118+/-57%, p=0.445) from baseline values in the 12 syndrome X patients compared with the 30 patients with negative exercise test results. In patients in the lowest quartile of coronary flow responses to acetylcholine, dobutamine increased systolic wall thickening by 121+/-73%; 3 had ischemic-appearing ST-segment depression during this stress. This contractile response to dobutamine was no different than the increase in systolic wall thickening (129+/-48%, p=0.777) in patients in the highest quartile of coronary flow responses, 3 of whom also had ischemic-appearing ST-segment depression during this stress. Thus, coronary endothelial dysfunction in the absence of coronary artery disease does not account for ischemic-appearing ST-segment depression in patients with chest pain despite normal coronary angiograms. Further, coronary endothelial dysfunction is not associated with myocardial contractile responses to stress consistent with myocardial ischemia.     

Arrhythmogenic ventricular aneurysms unrelated to coronary artery disease

Malignant ventricular tachycardia occurs most frequently in patients with coronary artery disease who have had a previous myocardial infarction and in whom a ventricular aneurysm subsequently develops in the scarred section of myocardium. Ventricular tachycardia in the presence of normal coronary arteries and a left ventricular aneurysm is unusual and can be refractory to medical therapy. We retrospectively reviewed our experience of 10 patients treated at our institution from 1983 to 1993. Age ranged from 22 to 76 years, and all patients presented with sustained ventricular tachycardia. All patients underwent complete electrophysiologic testing. Cardiac catheterization was performed in 9 patients, and each had normal coronary artery anatomy without evidence of significant fixed lesions. A left ventricular aneurysm, diagnosed by either echocardiography, thoracic cine computed tomography or magnetic resonance imaging, or ventricular angiography was present in all patients. Ventricular tachycardia could not be suppressed pharmacologically in 7 of 10 patients using multiple agents including procainamide, quinidine, flecanide, tocainide, propaferone, and amiodarone. Six patients were treated surgically by intraoperative electrophysiologic mapping, endocardial resection of foci, and left ventricular aneurysmectomy. An implantable cardiac defibrillation device was implanted in 2 patients. One patient died on the second postoperative day after simultaneous mapping -guided aneurysmectomy and implantable cardioverter defibrillator placement. There was one late postoperative death. All other surgically treated patients had postoperative electrophysiologic studies demonstrating no inducible ventricular tachycardia, and these patients remain without antiarrhythmic therapy in follow-up extending from 29 to 86 months (mean, 56 months).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impairment of exercise capacity and peak oxygen consumption in patients with mild left ventricular dysfunction and coronary artery disease

AIMS: Most studies in chronic heart failure have only included patients with marked left ventricular systolic dysfunction (i.e. ejection fraction < or =0.35), and patients with mild left ventricular dysfunction are usually excluded. Further, exercise capacity strongly depends on age, but age-adjustment is usually not applied in these studies. Therefore, this study sought to establish whether (age-adjusted) peak VO2 was impaired in patients with mild left ventricular dysfunction. METHODS: Peak VO2 and ventilatory anaerobic threshold were measured in 56 male patients with mild left ventricular dysfunction (ejection fraction 0.35-0.55; study population) and in 17 male patients with a normal left ventricular function (ejection fraction >0.55; control population). All patients had an old (>4 weeks) myocardial infarction. By using age-adjusted peak VO2 values, a 'decreased' exercise capacity was defined as < or = predicted peak VO2 - 1 x SD (0.81 of predicted peak VO2), and a severely decreased exercise capacity as < or = predicted peak VO2 - 2 x SD (0.62 of predicted peak VO2). RESULTS: Patients in the study population (age 52+/-9 years; ejection fraction 0.46+/-0.06) were mostly asymptomatic (NYHA class I: n=40, 76%), while 16 patients (24%) had mild symptoms, i.e. NYHA class II. All 17 controls (age 57+/-8 years) were asymptomatic. Mean peak VO2 was lower in patients with mild left ventricular dysfunction (23.6+/-5.7 vs 27.1+/-4.6 ml x min(-1) x kg(-1) in controls, P<0.05). In 75% of the study population patients (n=42) age-adjusted peak VO2 was decreased (NYHA I/II: n=29/13) and in 18% of them severely decreased (n=10; NYHA I/II: n=6/4). In contrast, only three patients (18%) in the control population had a decreased and none a severely decreased age-adjusted peak VO2. CONCLUSION: In patients with mild left ventricular dysfunction, who have either no or only mild symptoms of chronic heart failure, a substantial proportion has an impaired exercise capacity. By using age-adjustment, impairment of exercise capacity becomes more evident in younger patients. Patients with mild left ventricular dysfunction are probably under-diagnosed, and this finding has clinical and therapeutic implications.     

The association between a family history of type 2 diabetes and coronary artery disease in a type 1 diabetes population

The plasma protein beta2-glycoprotein I (beta2-GPI) is a major target of autoantibodies in patients with the antiphospholipid syndrome. To understand the physiological function of beta2-GPI and its potential role in the pathophysiology of the antiphospholipid syndrome, the binding of beta2-GPI to phospholipid membranes was characterized. The interaction of beta2-GPI with unilamellar vesicles containing varying amounts of acidic phospholipids with phosphatidylcholine (PC) was measured at equilibrium via relative light scattering. Analysis of binding isotherms gave apparent Kd values ranging from approximately 5.0 to 0.5 microM over a range of 5-20 mol % anionic phospholipid. Inhibition of binding by increasing ionic strength and Ca2+ ions suggests that binding is primarily electrostatic. These data indicate that beta2-GPI binding to membranes with physiological anionic phospholipid content is relatively weak in comparison to plasma coagulation proteins, suggesting that beta2-GPI does not function as a physiological anticoagulant based on its phospholipid-binding properties.     

Effect of acute alterations in afterload on left ventricular function in patients with combined coronary artery and peripheral vascular disease

The GTP analog guanylylmethylene diphosphonate (GppCH2p) strongly inhibited polyuridylic acid-directed polypeptide synthesis in a cell-free translation system prepared from Agrobacterium tumefaciens. Fusidic acid increased even further the inhibitory action. The pre-translocational ribosomal complexes formed with the GppCH2p and the elongation factor G protected the ribosome against the depurinating action of crotin 2 assayed as the acid-dependent release of the RNA fragment whose terminal sequence is 5'-GAGGACCGGGAUGGAC-3'. The results allowed to conclude that the interaction of both crotin 2 and the elongation factor G with the A. tumefaciens ribosomes in the pre-translocational state must take place at overlapping, either sterically or allosterically, ribosomal sites which are equally accessible to the RIP.     

Relation between left ventricular function and oxidative stress in patients undergoing bypass surgery

OBJECTIVE: To determine whether preoperative left ventricular ejection fraction (LVEF) is related to the degree of myocardial oxidative stress during bypass surgery in man. DESIGN: Observational study. SETTING: Tertiary care centre. PATIENTS AND INTERVENTIONS: 31 patients (LVEF range was 20% to 68%) undergoing elective coronary bypass surgery with blood cardioplegic reperfusion were studied. Arterial and coronary sinus blood was collected before aortic cross clamping (T0) and at 0 (T1), 15 (T2), and 30 (T3) minutes after unclamping. Transmural left ventricular biopsies were also obtained from 15 patients at T0 and at T1. MAIN OUTCOME MEASURES: Glutathione and adenine nucleotides were measured in myocardial biopsies, while coronary sinus-artery differences for glutathione, nucleotides, and products of lipid peroxidation were calculated from blood specimens. Creatine kinase (myocardial band; CK-MB) was measured in plasma at four and 12 hours after operation. RESULTS: Myocardial glutathione and adenine nucleotides were correlated (p < 0.02) with preoperative LVEF both at T0 (r = 0.909 and 0.672) and T1 (r = 0.603 and 0.605). Oxidised glutathione released from the heart during reperfusion was inversely correlated with LVEF (r = -0.448, -0.466, and -0461 at T1, T2, and T3, p < 0.01), while reduced glutathione (r = 0.519 and 0.640 at T1 and T2) and glutathione redox ratio (r = 0.647, 0.714, 0.645, and 0.702 at T0, T1, T2, and T3) showed a direct correlation (p < 0.01). Lipid peroxidation at T1 was negatively related to LVEF (r = -0.492). CK-MB was also negatively related to LVEF (r = -0.440 at 4 h and -0.462 at 12 h). CONCLUSIONS: The capacity to counterbalance oxidative burst following ischaemia and reperfusion appears to be related to the functional ability of the heart.     

Incidence of right ventricular asynergy in patients with coronary artery disease

The effects of coronary artery disease on patterns of left ventricular contractility have been thoroughly investigated. In contrast, little is known about the incidence of right ventricular dysfunction induced by this disease. To evaluate the frequency of right ventricular asynergy, biplane right ventricular cineangiograms were obtained in 26 patients. Seven segmental axes of shortening were analyzed in each end-systolic and end-diastolic frame and normalized as percent decrease (or increase) in axis from end-diastolic length. Of 26 patients, 8 (Group I) served as normal (control) subjects. The remaining 18 patients had significant coronary artery disease; 6 of these (Group II) had no significant disease of the right coronary artery, whereas 12 (Group III) had significant obstruction of this artery. Four patients in Group II had a previous anteroseptal myocardial infarction, and six in Group III had a previous inferior myocardial infarction. There was a progressive decrease in segmental axes of shortening from Group I to II and from Group II to II, but the decrease was not significant at the level P less than 0.01. Only one patient in Group II had frank dyskinetic segmental motion of the interventricular septum (this patient had had a previous anteroseptal myocardial infarction), whereas two patients in Group III had dyskinetic segmental motion of the free right ventricular wall (both had previous inferior myocardial infarction). Therefore, coronary artery disease seldom produces significant right ventricular asynergy. Abnormal septal motion is associated with previous anteroseptal myocardial infarction; however, dyskinetic motion of the free right ventricular wall occurs only in patients with a right coronary arterial lesion and previous inferior myocardial infarction.