Mitral valve prolapse in coronary artery disease.

Mitral valve motion, left ventricular segmental contraction and severity of arterial stenosis were analyzed in 92 patients with coronary artery disease and 28 patients with "atypical chest pain" and normal coronary arterio-rams. Mitral valve motion was evaluated for the presence or absence of leaflet prolapse. Segmental contraction was evaluated by calculating the percent shortening of six chords of the left ventricle measured from right anterior oblique ventriculograms. The severity of disease in each coronary vessel (left anterior descending, left circumflex and right coronary) was graded on a scale of 1 (0 to 30 percent stenosis) to 5 (complete occlusion). Mitral valve prolapse was not suspected clinically but observed angiographically in 15 of 92 patients with coronary artery disease and in 5 of 28 patients with normal coronary arteriograms. In nine patients with coronary artery disease, the prolapse was restricted to the posterior leaflet, in five it was in both the anterior and the posterior leaflets and in one patient in the anterior leaflet only. Mitral regurgitation was noted in seven patients with coronary artery disease; it was mild in six and moderate in one. Among the patients with coronary artery disease, 12 of the 15 (80 percent) with mitral valve prolapse had left ventricular asynergy compared with 63 of the 77 (82 percent) without valve prolapse. The mean scores for severity of disease in the left anterior descending, circumflex and right coronary arteries were, respectively, 4.2, 2.5 and 3.2 in the patients with valve prolapse and 4.2, 2.2 and 3.5 in those without prolapse. In summary, there was no significant correlation between mitral valve prolapse and distribution of coronary arterial obstructions or abnormal patterns of left ventricular segmental contraction. There was a high frequency of mitral valve prolapse in patients with severe coronary artery disease and in those with normal coronary arteriograms and atypical chest pain.     

Echocardiography in acute infectious myocarditis: Relation to clinical and electrocardiographic findings

Multidirectional M-mode echocardiography (echo) was used to investigate functional and structural changes of the heart in 68 consecutive patients with acute or subacute infectious myocarditis. Forty patients had mild myocardial involvement evident by gradually changing ST-segment or T-wave alterations (not responsive to β blockade) in serial ECGs; 21 patients also had loud S₃ gallop and palpable paradoxical cardiac pulsations, and 7 patients had severe congestive heart failure.Echo revealed regional changes in the left ventricular (LV) contraction in all patients with acute myocarditis. The site and size of the asynergic wall motion abnormalities correlated with both the clinical severity of the disease and the location of the T-wave inversions in the ECG. In mild myocarditis hypokinesia only was noted in 1 to 3 sites (mean 2.3) of 11 recorded LV sites (21%). In moderate myocarditis, the local asynergic change was mainly akinesia and more widespread, being surrounded by hypokinetic regions (3.8 of 11 sites, 35 % of the LV sites). In congestive heart failure, the hypokinetic or akinetic segments affected almost the entire left ventricle (7.6 of 11 sites, 69% of the LV sites) (p < 0.001 between the groups). In the last group, all patients had strong “fibrotic” echoes, in contrast to mild myocarditis (13%). In mild infectious myocarditis the contraction disturbance of the asynergic regions also generated a peculiar “quivering” pattern with thin echo lines. In the uninvolved segments, hyperkinesia was observed in most patients. The LV end-diastolic diameters in the 3 groups were 51 ± 5, 58 ± 4 and 65 ± 5 mm (p < 0.05), respectively. Thus, M-mode echo may provide a sensitive technique for detecting LV involvement in acute myocarditis and following its course.     

Muscle fiber disarray in common heart diseases.

Myocardial fiber disarray was found at necropsy in each of 53 hearts, 33 from patients with cardiovascular disease--systemic hypertension (12 patients), coronary heart disease (17 patients) or cor pulmonale (4 patients)--and 20 from patients with a normal heart. The myocardial fiber disarray was of mild degree in all 53 patients and, although similar to that observed by others in hearts of patients with hypertrophic cardiomyopathy, the amount of myocardial fiber disarray per heart was considerably less than that observed in patients with hypertrophic cardiomyopathy.     

Atrial myxoma in a family.

A family is described in which the mother and three of seven children had atrial myxoma. The mother had biatrial myxoma; surgical treatment resulted in massive intraoperative embolization and death. Surgery was sucessful in two sons with left atrial myxoma and systemic arterial embolization. A third son had calcified right atrial myxoma with destruction of the tricuspid valve and episodes of syncope and pulmonary embolism; surgery including valve replacement, was successful. The mother's father and a brother had died suddenly without a definite diagnosis. The family data are consistent with dominant transmission. The possibility of finding affected relatives should be borne in mind when studying patients with atrial myxoma.     

Progression of coronary artery disease in randomized medical and surgical patients over a 5-year angiographic follow-up

Progression of coronary artery disease (CAD) was assessed prospectively in a randomized series of 36 medically treated and 42 surgically treated patients with angina pectoris. The medical patients were reexamined after 5 years and the surgical patients 3 weeks, 1 year and 5 years after operation. Sixtyseven percent of the medical patients and 69% of the surgical patients had progression. The frequency of new lesions in initially normal segments after 5 years in the medical group was 6.7%, versus 4.1% in ungrafted normal segments in the surgical group (p = 0.05 < 0.010). The frequency of progression in abnormal arteries was 24.1% in the medical group, versus 22.6% in the ungrafted arteries of the surgical group (p = 0.90 < 0.95). The rate of progression of obstructed segments proximal to the graft over 5 years was 43%, versus 27% of the corresponding segments in the medical group (p < 0.01). Progression took place in 11.6% of normal segments proximal to the graft, versus 2% of the corresponding segments in the medical group (p < 0.05); 69% of progression occurring In segments proximal to the graft had reached total occlusion, versus 38% of the corresponding segments in the medical group (p < 0.01). Progression developed in 3.9% of segments distal to the graft, versus 3.1% of the corresponding segments in the medical group.Progression takes place at identical rates in medically treated patients and in ungrafted arteries and segments distal to the graft in surgical patients. Proximal to the graft the rates differ and total occlusions appear as early as 3 weeks after operation.     

Changes in native coronary arteries after coronary bypass surgery: Role of graft patency,serum lipids and hypertension

Sixty-seven patients were studied by coronary angiography early (mean 3 weeks) and late (mean 13 months) after coronary bypass surgery to assess changes in the native coronary vessels. Among the 208 nongrafted arteries progression of disease was found in 2.9 percent. In arteries that were normal before operation, the rate was 0.7 percent; in those with luminal obstructions the rate was 7.6 percent (P < 0.05). Progression of disease occurred in 6 of the 67 patients (8.9 percent). In five bypassed arteries (5 percent), progression of disease occurred at or near the anastomotic site; in this subset the procedure was classified a technical failure. Progression of disease distal to graft insertion occurred in 2.4 percent of cases. The greatest incidence of progression took place proximal to graft insertion, in 24.2 percent of the grafted arteries. This rate differed significantly from the rate in nongrafted arteries (P < 0.001) and in distal segments of grafted arteries (P < 0.001). If the grafts were patent in the late control study, the progression of disease proximally occurred at a rate of 24 percent; if they were occluded, the rate was 25 percent. The data on timing of graft occlusion suggested that graft patency was related to the proximal progression. The prevalence of hyperlipidemia or hypertension did not correlate with progression of disease in any group.     

Clinical results with gemfibrozil and background to the Helsinki Heart Study

The efficacy and safety of gemfibrozil in the treatment of dyslipidemia were investigated in a 6-year follow-up study of 254 patients with primary dyslipidemia. Most were middle-aged men with type IIA or IIB hyperlipoproteinemia. A significant correction in plasma lipid levels was seen in nearly 90% of all cases irrespective of the type of lipid abnormality. Overall, gemfibrozil therapy decreased levels of plasma total cholesterol 16%, triglycerides 45 % and low-density lipoprotein (LDL) cholesterol 21 %. The high-density lipoprotein (HDL) cholesterol concentration was increased 23%. The ratio of HDL cholesterol to total cholesterol increased from 0.13 to 0.20, approaching the value of matched controls in the population (0.23). Results in small pilot studies of patients with renal failure and uremia, the nephrotic syndrome or chemical diabetes were also encouraging. Plasma prekallikrein and kininogen values increased with gemfibrozil, possibly indicating correction of defective blood coagulation and fibrinolysis. Side effects were few; abdominal discomfort was noted in some patients and a skin rash in 2. In the intervention group, the number of myocardial infarctions was lower than expected (5 rather than 16). Results to date indicate that gemfibrozil effectively corrects most types of dyslipidemia, with minor side effects. The small number of observed myocardial infarctions supports the suggestion that an increase in HDL and a decrease in LDL levels during gemfibrozil therapy may be of clinical benefit in the prevention and management of coronary artery disease in subjects with dyslipidemia. The Helsinki Heart Study was designed as a definitive test of this hypothesis. This large, double-blind, placebo-controlled, primary (4,050 patients) and secondary (650 patients) prevention study is currently in progress.     

Effects of verapamil in patients with acute myocardial infarction: Hemodynamics and function of normal and ischemic left ventricular myocardium

We evaluated the effects of intravenous verapamil, a calcium antagonist, on hemodynamics and regional left ventricular (LV) performance in patients with acute myocardial infarction (AMI). Twenty patients having uncomplicated infarction or moderate heart failure were randomized to receive either verapamil or placebo and were studied a mean of 12 hours after onset of symptoms. Verapamil, 7.5 mg intravenously, acutely reduced systolic arterial pressure (p < 0.0005), systemic vascular resistance, and LV stroke work (p < 0.005) and rate-pressure product (p < 0.05); the heart rate did not alter. The Frank-Starling relationship by Swan-Ganz catheter did not change for 1 hour. Segmental wall motion amplitudes were recorded from eight standardized segments around the left ventricle by a multidirectional M-mode echocardiographic technique. The systolic wall motion of the uninvolved LV segments and LV cavity size did not change after verapamil. Verapamil improved mechanical performance in the ischemic segments (p < 0.005). Therefore, the overall regional contractile function of the left ventricle improved as well (by 11% to 13%, p < 0.05). This echocardiographic improvement continued after the acute vasodilatory response of intravenous verapamil subsided and was preserved for 1 week, the patients having had oral verapamil, 240 mg daily. Chest pain was relieved in five of the six patients having ongoing slight pain before verapamil injection. No sequential hemodynamic or echocardiographic changes occurred in the placebo-treated patients. Thus, in patients with uncomplicated AMI, verapamil improve contractile function of the acutely ischemic LV segments by hemodynamic unloading and/or by direct myocardial effect, without manifest depression of the uninvolved myocardium.     

Antiarrhythmic significance of dosing intervals in beta receptor blocking therapy of hypertension with acebutolol

Six hypertensive patients with daily ventricular arrhythmias underwent a double-blind crossover study to examine whether a once daily regimen of beta receptor blockade was equipotent in antihypertensive and antiarrhythmic activity to a twice daily regimen. Acebutolol, a relatively cardioselective beta blocking compound with intrinsic sympathomimetic properties, was given in two regimens: 200 mg twice daily or 400 mg once daily. Ventricular ectopic beats were analyzed both during physical exercise and with multiple 24 hour ambulatory electrocardiographic (Holter) recordings. Serum concentrations of acebutolol and its acetyl metabolite were determined using high pressure liquid chromatography. The two regimens of acebutolol were equally potent in reducing the blood pressure and heart rate at rest and during physical exertion. The hourly heart rates during 24 hours were reduced to the same extent by both regimens. The single daily 400 mg dose did not significantly reduce the incidence of arrhythmias, whereas 200 mg twice daily evoked a significant reduction during 24 hours. Serum concentrations of acebutolol were twice as great with the twice daily regimen as with the single dose. Both treatments significantly shortened the Q-Tc interval. The data suggest that, despite apparent beta receptor blockade and good blood pressure control, beta blocking agents with a relatively short plasma half-life lose their antiarrhythmic potency when administered on a once daily basis. This property seems to be more related to the plasma concentration of the compound than to the degree of clinically assessed beta receptor blockade.     

Noninvasive evaluation of the athletic heart: sprinters versus endurance runners.

To evaluate possible differences in the cardiac effects of different types of running training, 22 competing male runners--10 sprinters and 12 endurance runners--were studied with a physical examination, electrocardiography, chest X-ray film and echocardiography. Thirteen sedentary men served as control subjects. There were no differences between the athletic groups in physical findings. However, left ventricular hypertrophy in the electrocardiogram was more apparent in the endurance runners (P less than 0.05), whose relative heart size on chest X-ray examination was also greater than in the sprinters (P less than 0.02). On echocardiography the left ventricular end-diastolic volume was equally greater than normal in both groups of athletes (P less than 0.005), but in the endurance runners the percent chance of the minor axis diameter in systole was greater than in the sprinters or control subjects (P less than 0.02). Values for left ventricular wall thickness and mass were greater than normal in both groups of athletes but were higher in the endurance runners than in the sprinters (P less than 0.001). The left atrial diameter was apparently greater in the endurance runners than in the sprinters or control subjects (P less than 0.001), whereas that of the sprinters did not differ from normal. Thus, intensive sprinter training seems to dilate the left ventricle but causes less increase in wall thickness and mass than training for endurance running and no change in left ventricular function or left atrial size. Endurance running causes left ventricular dilatation equal to that of sprinter training, greater wall hypertrophy and improved systolic emptying of the left ventricle, and it also dilates the left atrium perhaps because of decreased left ventricular compliance.     

Serum lipoproteins in asymptomatic acute porphyria: no evidence for hyperbetalipoproteinemia

Hypercholesterolemia and elevated LDL cholesterol have previously been reported to be associated with acute porphyria. We therefore carried out a systematic study on serum lipoprotein levels in asymptomatic patients with acute porphyria. In 15 patients with acute intermittent porphyria and in seven with variegate porphyria, the total serum cholesterol as well as VLDL- and LDL-cholesterol concentrations did not differ from those of matched controls. On the other hand, the mean HDL-cholesterol concentration was significantly higher in patients with porphyria than in controls. Total serum triglycerides and triglycerides in various lipoproteins were normal in patients with porphyria. In contrast to earlier reports, we could not find increase of LDL cholesterol in asymptomatic acute porphyria. The results suggest that elevated HDL-cholesterol levels might occur in this group of porphyrias.     

Diastolic heart sound produced by mid-diastolic closure of the mitral valve

Mid-diastolic closure of the mitral valve is suggested as the source for an audible diastolic sound in a patient with aortic valve and coronary artery disease. On the apex cardiogram the sound followed the rapid filling wave by 60 msec and preceded the a wave. On the echocardiogram the sound corresponded to premature closure of the mitral valve in mid-diastole. In this case an audible diastolic sound that appeared to originate from mid-diastolic closure of the mitral valve indicated a rapidly increasing left ventricular diastolic pressure with severe left ventricular failure. After treatment of the congestive heart failure, the sound diminished in intensity.     

Lipoprotein lipase of adipose tissue and skeletal muscle in human obesity: Response to glucose and to semistarvation

Obesity is frequently associated with elevated plasma levels of triglyceride and very low density lipoproteins (VLDL). It is possible that this could be at least partly attributed to defective removal of triglycerides from circulation. Therefore, we studied the response of tissue lipoprotein lipase (LPL) activity to stimulation by glucose and to suppression by caloric deficiency in subjects with simple obesity and in nonobese controls. A five-hour intravenous infusion of glucose increased the LPL activity in both adipose tissue and skeletal muscle. The average rise was 2.5-fold in nonobese subjects but only 1.8-fold in obese patients (p < 0.05). The decrease of response was similar in obese subjects with and in those without hypertriglyceridemia suggesting that the change was due to obesity as such. During feeding a 400 cal diet for 7 days the LPL activity of obese subjects fell by an average of 50% in adipose tissue and by 40% in skeletal muscle. The decreases are smaller than previously found in nonobese human subjects in a similar experiment. The magnitude of decrease of LPL activity in both tissues was positively correlated with initial enzyme activity but was not influenced by serum triglyceride level. During starvation the HDL cholesterol levels were reduced the change being positively related to simultaneous decreases of LPL activity in adipose tissue and in skeletal muscle. It is concluded that the metabolic regulation of tissue LPL activity (of the heparin-releasable pool) is abnormal in obesity. This may be related to insulin resistance of obese people and it may explain why obese people are basically more prone to develop hypertriglyceridemia than lean ones. The resistance of LPL to caloric restriction in obese subjects could bear on difficulties in reducing the adipose tissue mass.     

High density lipoprotein subfractions and postheparin plasma lipases in alcoholic men before and after ethanol withdrawal

Serum lipoproteins (VLDL, LDL, HDL₂ and HDL₃) and postheparin plasma lipase activities were measured in 10 male alcoholic subjects at the end of a long drinking period and subsequently after 8 and 15 days of complete abstinence. None of the patients showed any clinical or histological evidence of cirrhosis or other alcoholic liver disease. Reference data were obtained from healthy normolipidemic nonalcoholic men of similar age. In spite of the heavy alcohol intake the serum triglyceride and VLDL triglyceride concentrations of the alcoholics were not different from those of the reference group. On the other hand, the LDL cholesterol of the alcoholics was remarkably low and did not rise significantly during the 2 wk of abstinence. The mean HDL cholesterol concentration of the alcoholic men was 54% higher than that of the controls. This was mainly due to elevation of HDL₂ (+63%) but also the HDL₃ cholesterol was higher than that of the control subjects (+20%). The phospholipid and protein concentrations of HDL₂ and the phospholipid of HDL₃ were also significantly increased in the alcoholic men in comparison with the controls. The composition of HDL subfractions of the alcoholics was only slightly abnormal with an increase of phospholipid and decrease of protein content of HDL₃. The concentration and composition of the HDL's returned to normal 1 wk after alcohol withdrawal. The postheparin plasma lipoprotein lipase and hepatic lipase activities of the alcoholic men were significantly higher than the respective values of the reference group. During eight off-alcohol days both enzyme activities decreased and reached the normal range. At the end of the drinking period no correlation was present between the levels of total HDL or its subfractions on the hand and any of the two lipase activities on the other. On the 8th off-alcohol day the HDL₂ phospholipid showed a highly significant positive correlation with lipoprotein lipase activity. It is concluded that the elevation of HDL during chronic use of alcohol in mainly due to increased concentration of HDL₂ and that this may be partly explained by an increase of lipoprotein lipase activity but that other mechanisms may also be involved. The low LDL concentration in alcoholic men without manifest liver disease is an interesting finding which should be studied further.     

Left ventricular response to isometric exercise and its value in predicting the change in ventricular function after mitral valve replacement for mitral regurgitation

Reduced left ventricular (LV) afterload and its effect on the resting ejection fraction may lead to over-estimation of LV function in mitral regurgitation (MR). To evaluate LV function during increased afterload of the heart, an isometric handgrip test was performed during cardiac catheterization in 15 patients with mitral regurgitation (MR group) and in 9 normal subjects (normal group). Twelve months after successful mitral valve replacement (MVR) the patients were recatheterized, and the value of preoperative stress testing in predicting the change in resting ventricular function after surgery was estimated.Isometric exercise caused an increase in end-systolic wall stress, a measure of ventricular afterload, in both the MR group and the control group (p < 0.001). The ejection fraction remained unchanged in the control group, but decreased from 0.58 ± 0.08 to 0.53 ± 0.08 in the MR group (p < 0.001). After MVR, end-systolic wall stress increased significantly (p < 0.001) and the ejection fraction decreased from 0.58 ± 0.05 to 0.51 ± 0.1 (p < 0.05). A positive correlation existed between the change in the ejection fraction during preoperative stress testing and the change in the resting ejection fraction after MVR (r = 0.65, p < 0.01). In 8 patients whose resting ejection fraction was within normal limits (> 0.55) preoperatively, the ejection fraction was depressed (< 0.55) 1 year after surgery. In all but 1 of these patients the isometric exercise revealed the reduced ventricular response to afterload stress preoperatively (decrease of the ejection fraction > 0.03 during exercise). Therefore, the isometric exercise-induced change in LV function appears to predict the influence of MVR on LV function.     

Ferritinemia with subnormal iron stores in lysinuric protein intolerance

To study the mechanism of ferritinemia in patients with lysinuric protein intolerance (LPI), an autosomal recessive disorder of diamino acid transport, we made a histologic evaluation of intracellular iron and/or ferritin in bone marrow and liver aspirates of 21 patients. We found no stainable iron in bone marrow cells. This was also the case in the liver in $\text{8}\text{9}$ of the patients. The hepatocytes were negative for ferritin particles in electron microscopy. The ferritin half-time in plasma was computed from the decrease in serum ferritin concentration during partial exchange transfusion. In the two patients tested the values were prolonged (95 and 65 min). We give evidence that in LPI serum ferritin is increased disproportionately to the size of iron stores in bone marrow reticulum cells and in the hepatocytes. We speculate that this inappropriate ferritinemia is due to impaired uptake of ferritin from plasma.     

Oral administration of urea cycle intermediates in lysinuric protein intolerance: effect on plasma and urinary arginine and ornithine

In lysinuric protein intolerance, an autosomal recessive disorder of amino acid transport, oral citrulline increases the plasma concentration of urea cycle intermediates more than does oral arginine or ornithine. The clinical improvement suggests that citrulline affords the best means of correcting the ornithinopenic malfunction of the urea cycle.