Ingemar Wallentin

Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy.

Adrenergic beta-blocking agents were given to 7 patients with advanced congestive cardiomyopathy who had tachycardia at rest (98 plus or minus 13 beats/min). The patients were on beta-adrenergic receptor blockade for 2 to 12 months (average 5-4 months). One patient was given alprenolol 50 mg twice daily and the other patients were given practolol 50 to 400 mg twice daily. Virus infection had occurred in 6 of the patients before the onset of symptoms of cardiac disease. All patients were in a steady state or were progressively deteriorating at the start of beta-adrenergic receptor blockade. Conventional treatment with digitalis and diuretics was unaltered or reduced during treatment with beta-blocking agents. An improvement was seen in their clinical condition shortly after administration of the drugs. Continued treatment resulted in an increase in physical working capacity and a reduction of heart size. Noninvasive investigations including phonocardiogram, carotid pulse curve, apex cardiogram, and echocardiogram showed improved ventricular function in all cases. The present study indicates that adrenergic beta-blocking agents can improve heart function in at lease some patients with congestive cardiomyopathy. Furthermore, it is suggested that increased catecholamine activity may be an important factor for the development of this disease, as has been shown in animal experiments.

PROLONGATION OF SURVIVAL IN CONGESTIVE CARDIOMYOPATHY BY BETA-RECEPTOR BLOCKADE

24 patients with congestive cardiomyopathy (group I) were compared with a group of 13 controls with similar clinical findings and myocardial function who were selected retrospectively (group II) . All patients received digitalis and diuretics, but group I patients received beta-blockers as well. The survival-rate in group I patients (83%, 66%, and 52% after one, two, and three years respectively) differed significantly from that in group II subjects (46%, 19%, and 10%, respectively). This finding is supported by the demonstration that beta-blockade improved myocardial function in group I subjects. It is therefore suggested that beta-blockade prolongs survival in patients with congestive cardiomyopathy.

Adverse effects of beta-blockade withdrawal in patients with congestive cardiomyopathy.

Fifteen patients with congestive cardiomyopathy who had improved conspicuously on chronic administration of a beta-blocker were studied after withdrawal of the drug. In six patients there was a pronounced deterioration of their clinical condition, and in all of the remaining patients there was a significant decrease in ejection fraction, and signs of compromised diastolic function with pathological apex curves and an increase in third heart sound. All these changes were reversed within a few weeks to a few months after readministration of beta-blocking drugs. This study supports the idea that an aetiological factor in congestive cardiomyopathy may be a pathological response to sympathetic stimulation which could be partly controlled by administration of beta-blocking drugs.

Orthogonal electrocardiogram, apex cardiogram, and atrial sound in normotensive and hypertensive 50-year-old men.

The prevalence of signs of heart involvement was studied non-invasively in a group of untreated hypertensives (n=35) and a reference group (n=73), all derived from a random population sample of 50-year-old men. Signs of left ventricular hypertrophy were studied by means of orthogonal electrocardiography and conventional electrocardiography. Signs of decreased distensibility of the left ventricle were studied by apex cardiography and registration of atrial sounds. Left ventricular hypertrophy among hypertensives was significantly more common according to orthogonal electrocardiography (33%) than according to conventional electrocardiography (9%), indicating that the former may be a better method for detection of left ventricular hypertrophy than the latter. In the hypertension group the amplitude of the R wave in lead X on orthogonal electrocardiography was positively correlated to casual diastolic blood pressure (r=0-40) and to diastolic blood pressure after one hours rest (r=0-65). The degree of pressure load leading to left ventricular hypertrophy seems to be better reflected by resting than by casual blood pressure. There was no hypertensive subject with both signs of left ventricular hypertrophy on orthogonal electrocardiography and either an a/H ratio over 15 per cent or an abnormal atrial sound, indicating two different forms of cardiac involvement as the result of hypertension. Casual blood pressures became normal during rest in hypertensives with a/H ratio over 15 per cent on apex cardiography or abnormal atrial sound, not in hypertensives with signs of left ventricular hypertrophy on orthogonal electrocardiography.

SODIUM EXCRETION AND SYMPATHETIC ACTIVITY IN RELATION TO SEVERITY OF HYPERTENSIVE DISEASE

The relationship between the severity of hypertensive disease and sodium excretion and sympathetic activity has been studied in subjects of the same age and sex derived from screening a total population. 19 untreated subjects with casual blood-pressure (B.P.) above 175/115 mm Hg on two separate occasions made up the hypertensive group. A normotensive group (n =19) was obtained by selecting a 5% random sample from all subjects with casual B.P. below 160/95. Sympathetic activity was determined from noradrenaline excretion and the severity of hypertension assessed by recording resting diastolic B.P., signs of left ventricular hypertrophy on orthogonal E.C.G., and the glomerular filtration-rate. In the hypertensive group the resting B.P. correlated well both with signs of left ventricular hypertrophy and with the glomerular filtration-rate--i.e., the degree of severity of the hypertension. Up to the level of 90 mm Hg resting diastolic B.P., sodium excretion rose in complete agreement with the theory of pressure diuresis. Above 90 mm Hg, however, sodium and noradrenaline excretion fell with increase of B.P. These two findings indicated that with increasing severity of hypertension the sodium balance overrides the sympathetic activity in the long-term regulation of B.P. This may have both prognostic and therapeutic implications.

Value of systolic and diastolic time intervals. Studies in normotensive and hypertensive 50-year-old men and in patients after myocardial infarction.

SUmAMRY Systolic and diastolic time intervals were studied non-invasively in a group of untreated hypertensives (n = 19) and a reference group (n = 36), all derived from a random population sample of 50-year-old men, and in a myocardial infarct group (n = 67) representative ofmen aged 48 to 57 years surviving infarction. The results showed that only the electromechanical interval, pressure rise velocity, and the interval between the aortic component of the second heart sound (A2) and the 0-point in the apex cardiogram were useful discriminants between the three groups. There were no significant differences in systolic time intervals between the groups and the systolic time intervals were of limited diagnostic value as signs of impaired left ventricular function. The infarct patients had a significantly longer electromechanical interval (34 ms) than individuals in the reference group (27 ms), indicating delayed start of the systolic contraction in the infarction group. The pre-ejection period predicted the isovolumetric contraction time with great uncertainty in the infarct group. Increased pressure rise velocity (resting diastolic blood pressure/isovolumetric contraction time >1200 mmHg/s) was seen in 38 per cent of the infarct patients and 67 per cent of the hypertensives, compared with 4 per cent in the reference group, indicating more powerful contraction in infarct patients and hypertensives as compared with subjects in the reference group. The difference could not be explained by a difference in preload as judged from the a-wave in the apex cardiogram. The A20 interval was significantly prolonged (>150 ms) in 74 per cent of the infarct patients and 56 per cent of the hypertensives, as compared with 3 per cent in the reference group, indicating prolonged relaxation or prolongation of the early filling phase of the left ventricle in hypertensives and infarct patients. This was mainly related to factors other than heart rate and blood pressure.

A Noninvasive Technique for Use in Cardiovascular Mass Surveys

Sektionen för Preventiv Kardiologi, Medicinska Kliniken I, Sahlgrenska Sjukhuset and Göteborgs Universitat, Göteborg, Sweden. Kliniska Fysiologiska Labatoriet, Sahlgrenska Sjukhuset and Göteborgs Universität, Göteborg, Sweden, * Department of Medicine (Cardiology), University College, Ibadan, Nigeria. (Address for requests for reprints and full numerical data.) Heart disease which has progressed to the point of overt myocardial failure usually has increased hazard of fatality before treatment can be effective and long-term results are poor. Attention is therefore increasingly directed towards recognition, within the community, of conditions known to precede such an event.