Mitral regurgitation following first-time acute myocardial infarction--early and late findings by Doppler echocardiography.

A total of 61 patients with first-time mild to moderate acute myocardial infarction and no reinfarction within the following 2 months were studied prospectively by Doppler echocardiography before hospital discharge and after 2 months to evaluate the prevalence of mitral regurgitation. Twenty-one age-matched healthy subjects served as controls. At baseline, the prevalence of Doppler-recorded mitral regurgitation was 74% and 29% in patients and controls, respectively. In the patients, the regurgitant flow measured by color flow Doppler was 1.04 cm2 (range 0.2-8 cm2) and occupied 7.5% (range 2-45%) of the left atrial area. Corresponding figures for controls were 0.35 cm2 (0.1-0.6) and 2.4% (0.7-4.5), respectively. On continuous wave Doppler, most patients (33/45) had Doppler signals similar to those of healthy controls. The prevalence of mitral regurgitation was about the same in anterior and inferior infarction (75 and 72% respectively). In the patients, the prevalence was similar after 2 months (79%) with minor changes in the Doppler characteristics of the regurgitation (regurgitant flow 1.12 cm2 and occupying 8.1% of left atrial area). The study demonstrates that in a group of patients with first-time mild to moderate myocardial infarction the prevalence of Doppler-recorded mitral regurgitation is high and mild in severity in the majority of the cases. The changes remain almost similar even after 2 months.

Characteristics of patients resistant to antihypertensive drug therapy.

In order to determine the features that characterize refractory hypertension (RH), patients aged less than 65 years in a hypertension clinic were screened. Thirty-six patients on triple drug therapy with a supine diastolic blood pressure (DBP) of greater than or equal to 5 mmHg above an identified target pressure (90-100 mmHg), or a systolic blood pressure (SBP) greater than or equal to 170 mmHg for the last 6 months (greater than or equal to 3 measurements) underwent a thorough clinical investigation. The frequency of renal artery stenosis (RAS) in the RH patients was 30%. The non-RAS patients had a low occupational status, 76% being either manual workers or unskilled non-manual workers (reference group: 42%; P less than 0.01). They were more obese (body mass index (BMI) 28.8 vs. 25.8; P less than 0.01), and had a longer duration of hypertensive disease. RH patients had a higher prevalence of non-insulin-dependent diabetes mellitus (18 vs. 6%; P less than 0.05), and showed a higher prevalence of nervous complaints and mental distress (44% vs. 12%; P less than 0.001) and musculo-skeletal pain (39% vs. 7%: P less than 0.001). It is suggested that refractory hypertension should be investigated and treated bearing psychosocial factors in mind, concurrently with a screening for secondary hypertension.

Comparability of echocardiography and chest X-ray following myocardial infarction.

In a group of 23 patients with first-time myocardial infarction (MI) we compared the results of echocardiography and chest X-ray as measured 1 week, 2 months, and 6 months following acute MI. Left ventricular end-diastolic dimension (LVEDd) and left atrial (LA) dimension were measured from the echocardiogram, and the cardiac volume in ml/m2 body surface area (BSA) was calculated from the chest X-ray. A progressive increase in LA dimension was noticed during the 6-month period: a significant increase after 2 months (P less than 0.001) with a further increase at 6 months compared with after 2 months (P less than 0.001). The changes in LA dimension were more pronounced in anterior and Q-wave infarction (P less than 0.001) than in inferior and non-Q-wave infarction (P less than 0.01). On the other hand, LVEDd showed a less conspicuous change: a moderate increase (P less than 0.05) at 2 and 6 months, also with a more pronounced change in anterior wall and Q-wave infarction (P less than 0.01). There was no significant concurrent change in the calculated heart volume in ml/m2 BSA, as measured from the chest X-ray. It is suggested that the observed changes in LA dimension reflect reduced left ventricular compliance after MI.

Decreased red cell filterability in patients with acute myocardial infarction.

The red cell filterability was decreased in patients with acute myocardial infarction (AMI) when compared with healthy controls, 14.6 (12.2-16.3) units and 16.9 (15.6-17.4) units respectively, P50 (P25-P75), p less than 0.001). No significant correlations could be seen within the AMI group between the decrease in filterability and the levels of serum aspartate aminotransferase or serum lactate dehydrogenase. The erythrocyte filterability, however, correlated to the serum concentrations of hepatic enzymes in AMI. The addition of sodium lactate in vitro in physiological concentrations (0.9-3.6 mM/l final concentration) lowered the erythrocyte filterability markedly to 2.7 (0-9.8) units in a dose-dependent manner, supporting the hypothesis that the decrease in erythrocyte filterability in AMI might be caused by an increase in the lactate concentration.

Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid.

Consecutive survivors of a myocardial infarction from the Southern Hospital, below 70 years of age, were randomized into a Control group (n = 276) and a Treatment group (n = 279). The latter was openly prescribed the combination of clofibrate and nicotinic acid for serum lipid lowering. Each patient should remain in the study for 5 years and be seen regularly every 4 months at a special IHD outpatient clinic within the hospital. The concentration of serum cholesterol and triglyceride was lowered by 13% and 19%, respectively, in the Treatment group compared to the Control group. Total mortality was 82 cases in the Control group and 61 in the Treatment group, a 26% reduction (p less than 0.05). For patients above 60 years of age in the Treatment group the reduction in mortality was 28% (p less than 0.05). IHD mortality was reduced by 36% (p less than 0.01) in the Treatment group compared to the Control group. The beneficial effect of the serum lipid lowering treatment was related to the serum triglyceride concentration in two ways. First, it only occurred in patients with a triglyceride level greater than 1.5 mmol/l (n = 216). Secondly, it was most pronounced in the 44% of the treated patients who had a lowering of the serum triglyceride by 30% or more, and in this subgroup the reduction of IHD mortality was 60% (p less than 0.01). For serum cholesterol there were no such relations. The difference between serum triglycerides and cholesterol concerning these relations to the treatment outcome may be due to the fact that hypertriglyceridaemia was the most common hyperlipidaemia among our patients, occurring in 50%, while hypercholesterolaemia only occurred in 13%. Caution should be exercised in the interpretation of the results as the trial was not blind. However, the fact that the decrease in IHD deaths was directly related to the degree of serum triglyceride lowering indicates that it was the drug effect on serum lipids that was responsible for the beneficial effect of the treatment.

Assessment of atrial contribution to left ventricular filling during cold pressor test by M-mode echocardiography in patients with coronary artery disease.

To determine whether temporarily increased afterload causes changes in left ventricular (LV) diastolic properties, we examined 19 patients with coronary artery disease (CAD) and 14 healthy subjects by M-mode echocardiography during immersion of the left hand in ice water. The M-mode echocardiograms were digitized to assess the percentage of atrial contribution (%AC) to LV filling as a marker of diastolic properties. Six patients and 5 controls had to be excluded owing to inability to clearly define the endocardium in the left ventricle throughout the entire heart cycle. In the control situation, the %AC did not differ significantly between the two groups. During the cold pressor test, the mean %AC at peak systolic and peak diastolic pressures was significantly higher in the CAD group than in the control group (p less than 0.05). Thus, by using M-mode echocardiography during the cold pressor test it is possible to document an increased atrial contribution to LV filling in patients with CAD. It is suggested that the mechanism is increased myocardial stiffness evoked by ischaemia with a resultant increased role of atrial contraction.

Echocardiographic left atrial dimension as a predictor of maintaining sinus rhythm after conversion of atrial fibrillation.

Twenty-six patients with lone atrial fibrillation were studied prospectively by M-mode echocardiography less than two months before and one month after cardioversion (CV). Seven patients had reverted to atrial fibrillation (AF) one month after CV. These patients (AF group) differed significantly with regard to mean left atrial dimension (LA) from the 19 patients (73%) who maintained sinus rhythm (S group) (p less than 0.001). Initial LA was 38.6 +/- 4.9 mm in the S group and 47.6 +/- 2.3 mm in the AF group. These values had not changed significantly in either group when measured one month after CV. The radiological heart size index showed a closely corresponding pattern. On the other hand, the mean heart size in both groups (441 +/- 100 and 544 +/- 98 ml/m2 BSA, respectively) was well below the upper normal limit (700 ml/m2) that is conventionally used as exclusion criterion from CV. In conclusion, in patients with AF and only moderate cardiac enlargement on chest X-ray, the echocardiographic LA can be used as predictor of maintaining sinus rhythm for at least one month following CV.

Orthostatic reactions during recovery from exhaustive exercise of short duration.

We studied the responses of six healthy volunteers to standard 70 degrees head-up tilt tests before exhaustive exercise of short duration (control) and after 5, 25, 50, 80, and 110 min of recovery, all tests lasting for 6 min except when impending syncope (IS) necessitated premature termination of a test. Marked impairment of orthostatic tolerance was apparent during the first half-hour of recovery as manifested by symptoms of IS in five subjects in one or both of the first two postexercise tilt tests. In none of the subjects who developed symptoms of IS did central venous pressure fall to a lower level than it did in the control test. From the central venous and arterial pressure reactions we conclude that when IS developed, declining systematic resistance rather than diminished cardiac filling was the responsive factor. The increased tendency for orthostatic collapse occurred during a period of recovery marked by persistent postexercise acidemia and hyperthermia suggesting interference of these conditions and associated events with the normal ability to vasoconstrict during orthostasis.

Responses to continuous negative-pressure breathing in man at rest and during exercise.

We studied the respiratory and circulatory effects in six healthy supine volunteers of continuous negative-pressure breathing (CNPB) at -15 and -30 cmH2O at rest and during dynamic leg exercies at 50% of individual working capacity. CNPB had no significant effects on respiratory minute volume, tidal volume, or arterial carbon dioxide tension. Mean arterial pressure remained essentially unchanged both at rest and during exercise, signifying that the reductions in intrathoracic pressure caused corresponding increases in left ventricular afterload. Nevertheless, cardiac output increased significantly in both conditions, causing reductions of mean central venous pressure that were considerably greater during exercise than at rest. These responses were reflected by increments in left ventricular work, amounting to 24 and 20% at rest and during exercise, respectively, at -30 cmH2O. We conclude that in CNPB at rest the increased activity of the left ventricle with associated juxtathoracic venous collapse protects the right heart and pulmonary circulation from congestion and that it does so even more effectively during exercise.

Respiratory and circulatory responses to sustained positive-pressure breathing and exercise in man.

To investigate the effects of sustained positive-pressure breathing (PPB) on the adaptation of respiratory and circulatory functions to exercise, 8 healthy volunteers were exposed to PPB of air at 15 and 30 cm H2O in the supine position at rest and while performing leg exercise at 50% of individual maximal working capacity. PPB was both subjectively and objectively better tolerated when combined with exercise than it was at rest. PPB at 30 cm H2O resulted in marked hyperventilation with alkalosis in the resting condition, but did not significantly affect respiratory minute volume, blood gases or acid-base balance during exercise. Cardiac output and left ventricular work were reduced by about one fifth and one third, respectively, both at rest and during exercise. In contrast to the case at normal airway pressure, exercise-induced increase in cardiac output was accompanied by an increment in stroke volume during PPB. Although mean arterial pressure (relative to atmospheric) was elevated by PPB at rest and during exercise, the driving pressure in systemic circuits (arterial minus central venous pressure) was reduced in both conditions. It is concluded that dynamic exercise counteracts deleterious effects of PPB by normalizing respiratory function and by improving cardiac filling by activation of the leg muscle and the abdominal pumps.

Kinetics of hemodynamic and electrocardiographic changes following intravenous disopyramide.

Changes in hemodynamic and ECG variables following disopyramide (1.7 mg = 3.9 mmol/kg b.wt.) were studied in 9 patients with ventricular arrhythmias. All patients displayed a marked reduction in the number of ventricular ectopic beats, all except one exhibiting complete abolition of the arrhythmia for at least 30 min. QT and QRS intervals showed statistically significant prolongations, and thereafter decreased exponentially with time. Above a certain concentration threshold that varied between the patients, systolic time intervals and aortic (dp/dt)max showed linear changes with increasing drug serum levels. Changes in diastolic pulmonary artery pressure showed no simple relationship with disopyramide concentration or time after injection. In 3 out of 4 patients studied, there was a good correlation between the lowest level of disopyramide that elicited both an antiarrhythmic effect and a demonstrable decrease in cardiac contractility.

Reduction of myocardial reinfarction by the combined treatment with clofibrate and nicotinic acid.

In an ongoing study 558 consecutive survivors of myocardial infarction below 70 years, mean age 59 years, were randomly allocated 4 months after the acute episode into a control group or a chemotherapy group from December 1972 to April 1976. Both groups were given moderate advice about diet and the chemotherapy group was prescribed clofibrate, 1 g twice daily, and nicotinic acid 1 g three times daily. Serum cholesterol and triglycerides were lowered around 15-20% and 30% respectively in the chemotherapy group while only insignificant reductions were observed in the control group. Until December 1976 total mortality and mortality from IHD has been the same in the two groups. The number of non-fatal myocardial infarctions has been 38 in the control and 19 in the chemotherapy group, a statistically significant reduction (P less than 0.01).

Lower body negative pressure and effects of autonomic heart blockade on cardiovascular responses.

Heart rate, arterial pressure and cardiac output were recorded in eight healthy male volunteers during exposure to 80 mmHg of lower body negative pressure (LBNP) in the supine position before and after beta-adrenergic and combined beta-adrenergic and parasympathetic blockade of the heart as induced by the i.v. administration of propranolol 0.25 mg/kg b.wt. and atropine 0.04 mg/kg b.wt. After propranolol, heart rate response to LBNP averaged 48% of that observed without blockade indicating that LBNP-induced cardioacceleration is of both sympathetic and parasympathetic origin. Tolerance to LBNP was reduced by beta-adrenergic blockade, since the decrease in mean arterial pressure during LBNP was exaggerated by such blockade. Although the addition of atropine markedly elevated mean arterial pressure and cardiac output in the control situation, tolerance to LBNP was not enhanced by this drug as judged from the arterial pressure response. Post-LBNP overshoot in mean arterial pressure was strikingly augmented by combined cardiac effector blockade and was in part due to a lingering elevation of total peripheral resistance, cardiac output remaining decreased for more than 110 s after release of LBNP.

Gravitational stress and autonomic cardiac blockade.

Arterial pressure, heart rate and cardiac output were recorded in eight healthy, male volunteers in the sitting position at normal gravity (1 G) and during a 4 min exposure in a human centrifuge to 3 G, the G vector in both conditions acting in the head-foot direction. The responses of the observed variables to the change from 1 G to 3 G were compared before and after combined beta-adrenergic and parasympathetic blockade of the heart induced by the i.v. administration of propranolol, 0.25 mg/kg bwt, and atropine, 0.03 mg/kg bwt. After blockade the heart-rate response to increased G averaged 22% of that observed without blockade. Mean arterial pressure at 3 G, and thus G tolerance, was significantly lowered after blockade, resulting in symptoms of retinal hypoxia ("greyout") towards the end of the 3 G runs in some of the subjects. G-induced reductions in cardiac output and stroke volume were significantly larger after blockade. Associated increases in total peripheral resistance were 56% before and 79% after blockade, the stronger vasoconstrictor response in the latter case thus being insufficient for maintenance of arterial pressure homeostasis.

Disopyramide in ventricular tachycardia.

Administration of disopyramide phosphate (DE) i.v. in two doses, 30 min apart, to a patient with ventricular tachycardia was accompanied by no, or only slight, changes in systemic arterial pressure (SAP), cardiac output (Q), stroke work (SW), and pulmonary artery diastolic pressure (PADP). Heart rate fell from 123 to 103/min. Following reversion to sinus rhythm, which occurred 60 min after the second dose of DE at a serum concentration greater than 4.3 mug/ml, Q ans SW showed significant increases above their control values. PADP fell from 20 to 6 mmHg whereas the mean SAP remained largely unchanged. There seemed to be no adverse effects of drug administration. In this patient, recurrent attacks of ventricular tachycardia not responding to conventional antiarrhythmic treatment could be prevented by oral DE in a dose of 800 mg/day.

Hemodynamic and electrocardiographic effects of disopyramide in patients with ventricular arrhythmia.

Antiarrhythmic and hemodynamic effects of i.v. disopyramide phosphate (1.7 mg/kg b.wt. over 2 min) have been studied in nine patients, several in various degrees of cardiac decompensation, with sinus rhythm and persistent ventricular ectopic beats (VEBs). In one case with primary cardiomyopathy, with greater than 30 VEBs/min, disopyramide (DE) abolished the arrhythmia for 30 min, but precipitated brief dysponea. Other side-effects were tolerable and mainly attributable to anticholinergic effects of the drug. DE either abolished or significantly reduced the arrhythmia in all cases. For 30 min, only one patient showed VEBs, and in three patients no VEBs were seen for three hours. Changes in cardiac output and pulmonary artery (PAP) and central aortic pressures were measured in eight patients. Negative inotropic effects were indicated in seven by an increased diastolic PAP/stroke volume ratio and in seven by a decreased central aortic (dp/dt)max. Patients with high control values for diastolic PAP showed marked reductions in cardiac output, stroke volume and stroke work. In predicting myocardial depressant effects of DE, the control values for diastolic PAP seemed to be superior to central venous pressure, cardiac index and systolic time intervals. Mean arterial pressure measured 5 and 10 min after drug administration showed no significant change, indicating that vasoconstrictor reflexes were well preserved, and a pressure level significantly above the control value was reached from the 20th min. It is concluded that DE is potent in suppressing VEBs but exerts negative inotropic effects that may be of clinical importance. The optimal antiarrhythmic dose is probably lower than that used in the present study.