Biomedical subjects
Publications and source records attributed to K I Lie.
The present data show that HR variability has a statistically significant, but moderate, correlation with clinical variables of severity of CHF. Therefore, HR variability analysis may be a new, important tool in the clinical assessment of CHF patients.
Few data are available about the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels. REGRESS is a double-blind, placebo-controlled, multicenter study to assess the effect of a 2-year treatment with the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis using quantitative coronary arteriography in 885 male patients with a total serum cholesterol value of 155-310 mg/dl (4-8 mmol/liter). Among symptomatic men with significant coronary atherosclerosis and normal to moderately raised levels of serum cholesterol, patients treated with pravastatin had less progression of coronary atherosclerosis and fewer new cardiovascular events than patients in the placebo group. Ultrasound examinations of carotid and femoral arteries were performed in 255 patients. Changes in intimal-medial thickness also showed a treatment effect from pravastatin; however, on a per patient basis, there was no correlation with the treatment effect in the coronary arteries.
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In the scientifically solidly based report 'Heart surgery and intervention cardiology for adults' the Dutch Health Council presents its advice relating to the expected developments in the area of invasive treatment of coronary diseases, mainly coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). The Council advocates combined cardiological-surgical discussions about indications for CABG and PTCA and central registration of data. Minimum requirements to guarantee quality of a treatment centre are the presence of 5 heart surgeons and 5 intervention cardiologists each performing 150 and 100 interventions a year, respectively. It is, according to the Council, not possible to determine the maximum size of a treatment centre scientifically. Concerning the waiting lists, the Council recommends a maximal waiting time of 2-3 months. It is interesting to follow the developments as on the one hand the Government wants to deregulate, whereas on the other it advocates a centralized approach.
BACKGROUND: Intensive lowering of serum cholesterol may retard progression of coronary atherosclerosis in selected groups of patients. However, few data are available on the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels who undergo various forms of treatment. The Regression Growth Evaluation Statin Study (REGRESS) addresses this group of patients. METHODS AND RESULTS: REGRESS is a double-blind, placebo-controlled multicenter study to assess the effects of 2 years of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis in 885 male patients with a serum cholesterol level between 4 and 8 mmol/L (155 and 310 mg/dL) by quantitative coronary arteriography. Primary end points were (1) change in average mean segment diameter per patient and (2) change in average minimum obstruction diameter per patient. Clinical events were also analyzed. Of the 885 patients, 778 (88%) had an evaluable final angiogram. Mean segment diameter decreased 0.10 mm in the placebo group versus 0.06 mm in the pravastatin group (P = .019): The mean difference between treatment groups was 0.04 mm, with a 95% CI of 0.01 to 0.07 mm. The median minimum obstruction diameter decreased 0.09 mm in the placebo group versus 0.03 mm in the pravastatin group (P = .001): The difference of the medians between the treatment groups was 0.06 mm, with a CI of 0.02 to 0.08 mm. At the end of the follow-up period, 89% (CI, 86% to 92%) of the pravastatin patients and 81% (CI, 77% to 85%) of the placebo patients were without new cardiovascular events (P = .002). CONCLUSIONS: In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group.
There is increasing evidence that clinical deterioration in manifest chronic heart failure is related to both hemodynamic and neurohumoral factors. Only few data are available, however, on the progression of disease in its early stages, when treatment has not yet been initiated. The aim of this study was therefore to examine the changes in clinical and neurohumoral variables that occur over 6 months in patients with clinically stable and untreated heart failure, and to evaluate the influence of drugs that may affect these variables. Accordingly, we studied 64 patients with heart failure who were in New York Heart Association functional class II (88%) and III (12%). They were randomized to double-blind treatment with the oral dopamine agonist ibopamine (100 mg 3 times daily; n = 22), digoxin (0.25 mg once daily; n = 22) or placebo (n = 20). Their age (mean +/- SD) was 60 +/- 8 years, and left ventricular ejection fraction (mean +/- SD) was 0.33 +/- 0.08. Of the 64 patients, 56 (88%) completed the 6-month study period (p = NS between groups). Exercise time decreased in patients treated with placebo after 6 months (median -62 seconds; p < 0.05 vs baseline), but it increased with ibopamine (+48 seconds), and digoxin (+17 seconds; both p < 0.05 vs placebo). Plasma norepinephrine increased in the placebo group after 6 months (median + 31 pg/ml, p < 0.05 vs baseline), but decreased in patients receiving active drug treatment (ibopamine: -24 pg/ml, digoxin: -98 pg/ml, both p < 0.05 vs placebo). Plasma renin and aldosterone levels were unchanged after 6 months in the placebo group, but digoxin therapy slightly reduced plasma renin concentration (-5 microU/ml; p < 0.05 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the additional diagnostic value of biplane transesophageal echocardiography (TEE) in patients undergoing mitral valve surgery, we studied 48 patients with severe mitral regurgitation. Transesophageal echocardiographic video recordings were reorganized in separate transverse and longitudinal sections to allow independent evaluation. Mechanism of mitral regurgitation and anatomic abnormalities of the mitral valve were assessed by all 3 transesophageal echocardiographic modalities and were related to surgical findings. Biplane TEE detected increased leaflet mobility with a sensitivity of 91% and a specificity of 84%, and restricted leaflet mobility with a sensitivity of 100% and a specificity of 97%. Biplane TEE was accurate in the diagnosis of most of the anatomic abnormalities associated with these mechanisms. However, the sensitivity for detecting subvalvular abnormalities (including papillary muscle abnormalities) was poor, and measurement of the annular diameter had a poor correlation with annular dilatation. Although the yield of biplane TEE was better than either transverse or longitudinal TEE alone, the differences did not reach statistical significance, because of the size of the patient group. The surgical procedure (either valve repair or replacement) was correctly predicted with transverse TEE in 71%, with longitudinal TEE in 69%, and with biplane TEE in 79% of the patients. All 3 transesophageal echocardiographic modalities are very capable of assessing the anatomic abnormalities and mechanism of mitral regurgitation, as well as predicting the feasibility of valve repair.
The choice between beta-blockade or nitrates as first line treatment for stable angina pectoris is based upon the different mechanisms of action and patient characteristics. We performed a clinical trial comparing the efficacy of the longacting beta-blocker bisoprolol once daily and the short acting nitrate, isosorbide dinitrate, three times daily in the reduction of anginal complaints in daily life and under stress. Thirty patients were enrolled in a double-blind randomised cross-over study. Both bisoprolol and isosorbide dinitrate were effective in reducing anginal attacks and nitroglycerin consumption significantly, but bisoprolol was significantly more effective than isosorbide dinitrate. Bisoprolol improved the workload during bicycle exercise testing significantly, but the improvement with isosorbide dinitrate was not significant. Despite the reduction in maximal rate pressure product, bisoprolol was significantly (P < 0.05) more effective at improving total workload and reducing the time to onset of angina than isosorbide dinitrate. The rate pressure product did not change significantly with isosorbide dinitrate. In this study, bisoprolol 10 mg once daily was more effective and caused less side effects than isosorbide dinitrate 20 mg three times a day. It seems questionable if monotherapy of isosorbide dinitrate 20 mg t.i.d is an adequate drug regime for stable angina pectoris.
We studied heart rate variability in ambulatory electrocardiographic recordings from 312 patients with significant coronary artery disease and a left ventricular ejection fraction of > or = 30%. Only those patients who had both episodes of ischemia and nonsustained ventricular arrhythmias showed diminished values for parasympathetic nonspectral and spectral heart rate (HR) variability parameters. The root mean square of difference of successive R-R intervals (RMSSD) and high-frequency (HF) power in this group were 28 +/- 3 msec and 9 +/- 1 msec, respectively. The highest values of these HR variability parameters were found in patients with nonsustained ventricular tachycardia and no ischemia (81 +/- 21 msec and 14 +/- 1 msec, respectively, p < or = 0.05). A relation was seen between transient myocardial ischemia and low-frequency power and between transient ischemia and ventricular tachycardia. These data suggest that the autonomic nervous system may play a role in ischemia and in ischemia-related ventricular arrhythmias.
To study prognostic factors in patients with sustained ventricular tachycardias (VT) or ventricular fibrillation (VF) complicated by left ventricular dysfunction, we evaluated the predictive value of demographic, clinical, and hemodynamic parameters for cardiac mortality and sudden cardiac death in 85 patients with VT or VF and left ventricular ejection fraction < 0.45 (mean 0.27 +/- 0.10). Patients underwent serial drug testing and received appropriate antiarrhythmic treatment, with amiodarone given as last-resort therapy. During a follow-up of 24 +/- 13 months, 23 patients died of cardiac causes, and 18 of them died suddenly. Left ventricular ejection fraction < or = 0.27 and amiodarone treatment were related to greater cardiac mortality and increased risk of sudden cardiac death, whereas beta-blockade was associated with improved survival. In the multivariate model cardiac mortality was best predicted by a left ventricular ejection fraction < or = 0.27, and absence of beta-blockade and severe left ventricular dysfunction were the strongest predictors of sudden cardiac death. We conclude that severe left ventricular dysfunction predicts increased cardiac mortality and high risk of sudden cardiac death. Moreover, beta-blocking treatment is associated with lower cardiac mortality and a reduced risk of sudden cardiac death in patients with sustained VT or VF and depressed left ventricular function. beta-Blocking agents may therefore be an important addition to conventional antiarrhythmic treatment in patients with VT or VF and left ventricular dysfunction.
Two patients are described with reproducible cardiac asystole post-exercise. No structural heart disease was demonstrable. At autonomic function testing no abnormal responses were noted. Also, head-up tilt tests were normal. However, electrophysiologic testing and heart rate variability during 24-h Holter monitoring were indicative of a high vagal tone in both patients. The findings suggest that post-exertional asystole may not be due solely to a vasovagal mechanism; excessive rebound vagotonia per se may also play a role.
OBJECTIVES: This study assessed the effects of digoxin and ibopamine on variables of heart rate variability in relation to neurohormonal activation. BACKGROUND: Analysis of heart rate variability can be used to study the autonomic dysfunction that characterizes chronic heart failure. In the Dutch Ibopamine Multicenter Trial, patients with heart failure were found to have increased neurohormonal activation with placebo therapy but not with digoxin and ibopamine therapy. METHODS: We studied 59 patients with mild to moderate heart failure (mean [+/- SEM] age 60 +/- 1 years, mean ejection fraction 0.30 +/- 0.01). Patients were randomized to double-blind treatment with digoxin (0.25 mg [n = 22]), ibopamine (100 mg three times a day [n = 19]) or placebo (n = 18); background therapy consisted of furosemide (up to 80 mg). RESULTS: After 3 months, plasma norepinephrine levels had increased with placebo, whereas they decreased with digoxin (+31 vs. -60 pg/ml, respectively, p < 0.01). With ibopamine, nonsignificant decrease was observed (-27 pg/ml, p = 0.10). All variables of heart rate variability showed a deterioration in the placebo group. With digoxin, the percent differences between successive RR intervals > 50 ms (pNN50) increased (+ 1.7 +/- 0.9%, p < 0.01), along with absolute and normalized high frequency power (+ 40 +/- 33 ms2, p < 0.05 and + 2.4 +/- 1.7%, p < 0.01, respectively). These changes were observed during daytime hours only and were most pronounced in patients with the most impaired baseline heart rate variability. With ibopamine, nonsignificant trends similar to the changes with digoxin were observed. CONCLUSIONS: In patients with early stages of heart failure, digoxin may prevent a progressive deterioration in heart rate variability, whereas ibopamine does not show statistically significant effects. The changes in heart rate variability with digoxin parallel an observed decrease in neurohormonal activation. Digoxin apparently enhances cardiac vagal tone in the setting of neuroendocrine activation.
Although atrial fibrillation is common in patients with heart failure, patients with atrial fibrillation are often excluded from congestive heart failure trials or are not analyzed separately. Consequently, while the effect of angiotensin-converting enzyme inhibitors in patients with sinus rhythm is well established, the effect on patients with atrial fibrillation is unknown. The authors hypothesized that these agents might be particularly effective in this patient category, given their antiadrenergic properties and the importance of adequate rate control. Therefore, the effects of lisinopril 10 mg once daily were evaluated in 30 patients with congestive heart failure and chronic atrial fibrillation (mean age, 68 +/- 6 years) in a double-blind, randomized, placebo-controlled trial. All patients were in New York Heart Association class II or III and were stable on conventional therapy (digoxin, diuretics, nitrates). After 6 weeks, mean peak oxygen consumption increased from 14.7 +/- 3.4 to 15.9 +/- 2.9 mL/min/kg in the lisinopril group (P = .034). Plasma norepinephrine levels during exercise and at peak exercise tended to be lower when the patients were taking lisinopril (10.8 +/- 4.2 to 8.9 +/- 4.4 nmol/L and 16.3 +/- 9.2 to 14.3 +/- 7.7 nmol/L, P < .1). Heart rate during exercise and ambulatory monitoring was not significantly affected. Left ventricular fractional shortening tended to increase after lisinopril (23 +/- 7 to 27 +/- 9%, P = .073). Left atrial volume was unchanged, as were plasma atrial natriuretic peptide levels. After subsequent electrical cardioversion, treatment was continued for 6 more weeks, allowing assessment of the effect of lisinopril on maintenance of sinus rhythm; maintenance of sinus rhythm was 71% in the lisinopril group and 36% in the placebo group (P = NS). This study shows that treatment with an angiotensin- converting enzyme inhibitor improves peak oxygen consumption in patients with congestive heart failure and chronic atrial fibrillation. Attenuation of adrenergic drive during exercise may play a role in mediating this effect.
The fundamental abnormality in syndrome X (angina pectoris, ischaemia-like stress ECG despite angiographically normal coronary arteries) might be patchily distributed increased tone in pre-arteriolar coronary vessels with compensatory release of adenosine. The aim of this study was to confirm this hypothesis and to explore its relationships with autonomic system functioning. Using parametric positron emission tomography, myocardial perfusion was examined in 480 segments in 16 syndrome X patients and 16 age- and sex-matched healthy volunteers. Autonomic function was explored by Holter monitoring of time domain parameters of heart rate variability. Compared to volunteers, both mean perfusion (123 +/- 35 vs 87 +/- 16 mg.min-1.100 g-1; P < 0.01) and its coefficient of variation (17.0 +/- 3.2 vs 13.6 +/- 2.2%; P < 0.01) as a measure of perfusion heterogeneity, were higher in patients with syndrome X. In contrast to the findings in the control subjects, patients showed an inverse relationship between perfusion heterogeneity (coefficient of variation of segmental perfusion) and autonomic tone (heart rate variability parameters). Since marked perfusion heterogeneity (inversely related to autonomic tone) and higher overall perfusion were found, the study supports the data that in syndrome X hyperreactivity of small coronary vessels with compensatory release of adenosine may be patchily distributed.
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This study was performed because of observed differences between dye dilution cardiac output and the Fick cardiac output, calculated from estimated oxygen consumption according to LaFarge and Miettinen, and to find a better formula for assumed oxygen consumption. In 250 patients who underwent left and right heart catheterization, the oxygen consumption VO2 (ml.min-1) was calculated using Fick's principle. Either pulmonary or systemic flow, as measured by dye dilution, was used in combination with the concordant arteriovenous oxygen concentration difference. In 130 patients, who matched the age of the LaFarge and Miettinen population, the obtained values of oxygen consumption VO2(dd) were compared with the estimated oxygen consumption values VO2(lfm), found using the LaFarge and Miettinen formulae. The VO2(lfm) was significantly lower than VO2(dd); -21.8 +/- 29.3 ml.min-1 (mean +/- SD), P < 0.001, 95% confidence interval (95% CI) -26.9 to -16.7, limits of agreement (LA) -80.4 to 36.9. A new regression formula for the assumed oxygen consumption VO2(ass) was derived in 250 patients by stepwise multiple regression analysis. The VO2(dd) was used as a dependent variable, and body surface area BSA (m2). Sex (0 for female, 1 for male), Age (years), Heart rate (min-1) and the presence of a left to right shunt as independent variables. The best fitting formula is expressed as: VO2(ass) = (157.3 x BSA + 10.0 x Sex - 10.5 x In Age + 4.8) ml.min-1, where ln Age = the natural logarithm of the age. This formula was validated prospectively in 60 patients. A non-significant difference between VO2(ass) and VO2(dd) was found; mean 2.0 +/- 23.4 ml.min-1, P = 0.771, 95% Cl = -4.0 to +8.0, LA -44.7 to +48.7. In conclusion, assumed oxygen consumption values, using our new formula, are in better agreement with the actual values than those found according to LaFarge and Miettinen's formulae.
UNLABELLED: In acute studies ibopamine, an a selective dopamine agonist, induces moderate increases of GFR and ERPF, and a fall in plasma norepinephrine levels in patients with congestive heart failure (CHF). We evaluated acute and chronic effects of ibopamine on renal haemodynamics, sodium excretion, PRA, plasma aldosterone (ALD) and norepinephrine levels in an open controlled study in 10 patients aged (51-79 years) with mild CHF, NYHA class II-III. All patients used digoxin and frusemide. After a control study day, the second study day involved the administration of 100 mg ibopamine. Subsequently the patients continued to take ibopamine 100 mg three times daily for one month, at which time the chronic effects were measured on the third study day. RESULTS: On the second day ERPF rose from a baseline of 288 +/- 32 to a mean of 308 +/- 32 ml.min-1 x 1.73 m-2 (P < 0.05) during the 4 h after the first administration of ibopamine and GFR rose from 77 +/- 8 to a mean of 84 +/- 8 ml.min-1 x 1.73 m-2 (P < 0.05). The ratio GFR/ERPF, representing the filtration fraction (FF) remained unchanged. On the third study day GFR and ERPF at baseline were similar to those before ibopamine treatment. After the acute on chronic administration we observed an increase in GFR (from 76 +/- 6 to a mean of 85 +/- 7 ml.min-1 x 1.73 m-2 (P < 0.05)), and in ERPF (from 279 +/- 27 to a mean of 293 +/- 29 ml.min-1 x 1.73 m-2 (P < 0.05)). Plasma norepinephrine levels fell from 2.63 +/- 0.48 to 1.92 +/- 0.27 nmol.l-1 (P < 0.05) after the acute administration of ibopamine, and remained unchanged after the acute on chronic ibopamine administration (C: 1.80 +/- 0.42 nmol.l-1). No changes in sodium excretion were observed, either in blood pressure, heart rate, PRA or ALD. We conclude that renal function is preserved during chronic ibopamine treatment and the acute moderate increase of ERPF and GFR after a single dose of 100 mg of ibopamine is still present after one month of treatment with ibopamine in patients with CHF. Ibopamine lowered plasma norepinephrine levels in our patients with CHF, and these values remained unchanged after the acute on chronic administration of ibopamine.
The aim of the present study was to examine the relationship between randomness of atrial and ventricular rhythm during atrial fibrillation. Atrial fibrillation was induced in 10 open-chest pigs by application of metacholine on the surface of the right atrium followed by incremental pacing. Local atrial rhythm (AA intervals) was recorded with a bipolar epicardial electrode, and episodes of atrial fibrillation corresponding to 500 ventricular (RR) intervals were selected for analysis. Randomness of the distribution of AA and RR intervals was assessed by autocorrelation. Pearson's test was used for statistical analysis. Random AA and RR interval distribution was observed in nine pigs (P > or = 0.05). In the remaining pig, atrial fibrillation had changed to atrial tachycardia. This was associated with immediate transition of a random to a non-random ventricular rhythm. These findings provide strong circumstantial evidence in support of the contention that randomness of ventricular rhythm during atrial fibrillation is due to randomness of atrial rhythm.