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Biomedical subjects

F X Kleber

Publications and source records attributed to F X Kleber.

At least 19 recordsLinked to original sources
PubMed1998

Ventilatory efficiency and exercise tolerance in 101 healthy volunteers.

The ventilatory equivalent for CO2 defines ventilatory efficiency largely independent of metabolism. An impairment of ventilatory efficiency may be caused by an increase in either anatomical or physiological dead space, the latter being the most important mechanism in the hyperpnoea of heart failure, pulmonary embolism, pulmonary hypertension and the former in restrictive lung disease. However, normal values for ventilatory efficiency have not yet been established. We investigated 101 (56 men) healthy volunteers, aged 16-75 years, measuring ventilation and gas exchange at rest (n = 64) and on exercise (modified Naughton protocol, n = 101). Age and sex dependent normal values for ventilatory efficiency at rest defined as the ratio ventilation:carbon dioxide output (VE:VCO2), exercise ventilatory efficiency during exercise, defined as the slope of the linear relationship between ventilation and carbon dioxide output (VE vs VCO2 slope), oxygen uptake at the anaerobic threshold and at maximum (VO2AT, VO2max, respectively) and breathing reserve were established. Ventilatory efficiency at rest was largely independent of age, but was smaller in the men than in the women [VE:VCO2 50.5 (SD 8.8) vs 57.6 (SD 12.6) P < 0.05]. Ventilatory efficiency during exercise declined significantly with age and was smaller in the men than in the women (men: (VE vs VCO2 slope = 0.13 x age + 19.9; women: VE vs VCO2 slope = 0.12 x age + 24.4). The VO2AT and VO2max were 23 (SD 5) and 39 (SD 7) ml O2 x kg x min(-1) in the men and 18 (SD 4) and 32 (SD 7) in the women, respectively, and declined significantly with age. The VO2AT was reached at 58 (SD 9)% VO2max. Breathing reserve at the end of exercise was 41% and was independent of sex and age. It was concluded from this study that ventilatory efficiency as well as peak oxygen uptake are age and sex dependent in adults.

Adolescent↗
PubMed1998

Invasive strategies to discriminate stable and unstable coronary plaques.

Unstable coronary plaques with surface erosion and plaque rupture lead to acute coronary thrombosis, unstable angina pectoris and myocardial infarction. The in-vivo detection of plaque instability by angiography, intravascular ultrasound or angioscopy or by newly developed techniques, such as optical coherence tomography or by the observation of local temperature increases, offers the opportunity for deeper understanding of the mechanisms underlying plaque rupture and erosion. Pharmacological and transcatheter therapy might be directed more exclusively to unstable plaques, once more detailed knowledge about pathophysiological mechanisms as well as direct information about the individual plaque being treated is available.

Angioscopy↗
PubMed1997

Angiotensin-converting enzyme inhibitors in preventing remodeling and development of heart failure after acute myocardial infarction: results of the German multicenter study of the effects of captopril on cardiopulmonary exercise parameters (ECCE).

Early action of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction (MI) has been shown in large scale clinical trials to reduce mortality over the first weeks. However, the mechanisms involved are yet unclear and several trials showed a tendency toward a small, albeit unexpected, rise in cardiogenic shock or mortality. Since cardiopulmonary exercise testing (CPX) has become a "gold standard" in assessing the severity of heart failure, we studied--after finishing a pilot trial--the effect of captopril versus placebo in 208 patients who were individually titrated (titrated dose, mean 46/69 mg/day after 7 days/4 weeks, respectively) in order to preserve their blood pressure in the acute phase of myocardial infarction; we followed the development of congestive heart failure (CHF) over 4 weeks by measuring oxygen consumption. After 4 weeks, overall oxygen consumption at the anaerobic threshold (VO2-AT; 13.7 vs 13.1), maximal oxygen consumption (VO2max 19.3 vs 18.9 mL/kg per min) and exercise duration (896 vs 839 sec) showed a nonsignificant difference in favor of the captopril group. The predefined, categorized, combined endpoint of severe heart failure or death (heart failure necessitating ACE inhibition, VO2max < 10 mL/kg per min, or death) was significantly reduced in the captopril group (n = 7/104) versus placebo (n = 18/104; p = 0.03). Differences were mainly caused by fewer CHF events (delta n = 10). We conclude that ACE inhibition with individualized dose titration markedly reduces the 4-week incidence of severe heart failure or death; > 10 patients per 100 treated gained major benefits from this therapy.

Adult↗
PubMed1997

Short-term hemodynamic effects of immunoadsorption in dilated cardiomyopathy.

BACKGROUND: Previous studies have shown that the sera of many patients with dilated cardiomyopathy (DCM) are positive for several antibodies directed against cardiac antigens. Anti-beta1-adrenergic receptor antibodies occur in 70% to 90% of DCM patients. These antibodies are extractable by immunoadsorption (IA). In an investigation of the functional significance of antibodies for hemodynamics, IA was performed throughout 5 consecutive days on nine patients with severe DCM who were on stable drug therapy. METHODS AND RESULTS: Immunoglobulins were eliminated in nine patients with severe DCM (mean age, 43.5 years; range, 25 to 58 years; left ventricular ejection fraction, <25%). IA was performed over 5 consecutive days with an immunoadsorber for immunoglobulin. All patients were on stable medication, including ACE inhibitors, digitalis, and diuretics. All patients received beta-blockers. During therapy, hemodynamic parameters (mean+/-SD) were monitored with a Swan-Ganz thermodilution catheter. IA elicited a decrease of anti-beta1-adrenergic receptor antibodies from 6.4+/-1.3 to 1.0+/-0.5 relative units. During IA, cardiac output increased from 3.7+/-0.8 to 5.5+/-1.8 L/min, P<.01. Mean arterial pressure decreased from 76.0+/-9.9 to 65.0+/-11.2 mm Hg, P<.05; mean pulmonary arterial pressure, from 27.6+/-7.7 to 22.0+/-6.5 mm Hg, P<.05; left ventricular filling pressure, from 16.8+/-7.4 to 12.8+/-4.7 mm Hg, P<.05; and systemic vascular resistance, from 1465+/-332 to 949+/-351 dyne x s x cm(-5), P<.01. CONCLUSIONS: In addition to conventional medical treatment, IA may be an additional therapeutic possibility for acute hemodynamic stabilization of patients with severe DCM.

Adult↗
PubMed1997

Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators.

BACKGROUND: Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study. METHODS: Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done. FINDINGS: After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients. INTERPRETATION: Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.

Adult↗
PubMed1997

Dynamic three-dimensional echocardiography in the assessment of cor triatriatum.

Classic cor triatriatum sinistrum is a rare cardiac malformation to be found in the adult. One year after surgical correction of an atrial septal defect in a 55-year-old man, cor triatriatum sinistrum was diagnosed by transesophageal echocardiography. We compared transthoracic echocardiography, transesophageal echocardiography, and cardiac catheterization to dynamic three-dimensional echocardiography (3-D echo) which offers a new, noninvasive approach to determine the opening size between the accessory and the true left atrium. The findings by 3-D echo, confirmed by left heart catheterization, showed that the accessory membrane was not stenosing. Surgical correction was therefore not indicated in this patient.

Cardiac Catheterization↗
PubMed1997

Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease.

Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results. Therefore we examined the association of the DNA variants of ACE and AGT with early, severe coronary heart disease (CHD). In addition, we compared the genotypes of both polymorphisms and the recently discovered polymorphism in the E-selectin gene in both patients and an unselected population. This study included 113 patients with severe CHD (50 years old or less) and up to 197 control subjects. The frequencies of the ACE I/D variants were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls and 49.1% M and 50.9% T in the patients. The frequencies of the S128R polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S and 15.5% R in the patients. In our studies the DD genotype of ACE was not associated with early severe CHD. We found a correlation between the M235T molecular variant of AGT and the S128R variant of E-selectin to early severe CHD.

Adult↗
PubMed1997

[Aerosolized prostacyclin for preoperative evaluation and post-cardiosurgical treatment of patients with pulmonary hypertension].

BACKGROUND: Inhaled nitric oxide (NO) has been shown to selectively lower pulmonary vascular resistance and is applied in patients with pulmonary hypertension (PHT). However, application and monitoring is complex and not always successful ("non-responders"). We evaluated the effect of aerolized prostacyclin (aePGI2) as a therapeutic alternate to NO. PATIENTS AND METHODS: aePGI2 and NO were applied to patients with different causes of pulmonary hypertension (Group 1a: preoperative patients with intracardiac shunting defects and Eisenmenger's disease, n = 30; Group 1b: patients with primary or postoperative PHT, n = 13; Group 2: PHT immediately following surgery for congenital heart disease, n = 6). RESULTS: Pulmonary vascular resistance could be lowered significantly (Group 1a: from 91% of systemic vascular resistance to 58% with NO and 53% with aePGI2; Group 1b: from 20.2 Wood Units*m2 to 13.4 and 11.3; Group 2: from 24.9 Wood Units*m2 to 9.5 and 10.5); cardiac index increased (Group 1b: from 2.96 to 3.55 and 3.96 l/min*m2, Group 2: from 1.57 to 1.89 and 2.00 l/min*m2). CONCLUSIONS: The short-term application of aePGI2 shows a selective pulmonary vasodilation similar to NO. Given adequate monitoring, aePGI2 appears to be useful for the acute treatment of PHT.

Administration, Inhalation↗
PubMed1997

[Histologic specimen collection in pulmonary hypertension using percutaneous, transvascular biopsy--animal experiment and initial clinical data].

Pulmonary hypertension is a severe multietiological disease largely resistant to treatment. Biopsy is often necessary to establish differential diagnosis. In pulmonary hypertension transbronchial pulmonary biopsy is contraindicated and open lung biopsy is the method of choice. In our paper we report about experimental results in animals and first clinical data on a new biopsy technique (percutaneous transluminal biopsy, PTB) providing access to histology in pulmonary hypertension without the need of surgery. In a subset of animals pulmonary hypertension was produced experimentally. In addition, we carried out the PTB in patients with bronchial carcinoma. Our preliminary results demonstrate that sufficient material could be gained for the histologic evaluation of pulmonary parenchyma and in pulmonary vessels. No complications have been noted so far.

Animals↗
PubMed1997

[Rupture of PTCA balloons--an in vitro study].

A large number of PTCA balloon catheters from different manufacturers were examined following their use. Several of these balloons had been previously used for PTCA for the mere purpose of guide wire support. Each balloon was evaluated starting at 8 atm. The pressure was increased in steps of 1 atm until rupture. This stepwise increase of pressure was documented at each level in a short cine film. During dilatations, balloons were in room air until rupture. None of the balloons ruptured before the rated burst pressure. A few of the balloons tolerated pressures of approximately 27 atm. With increasing pressure the shape of the balloons became distorted. Most assumed a banana shape. Most of the balloons ruptured after developing a small hole. Increasing pressure produced increasing diameter, and, generally, we found a linear increase. Most balloons increased by > 15% in diameter over the nominated diameter before rupture. The burst pressure in all balloons was not influenced by the prior mode of dilation, duration of dilation, maximum pressure applied, or length of the balloon. Balloons with smaller diameter ruptured later than compared to those with larger diameters. Our findings demonstrated that all of the balloons tolerated the manufacturers' recommended inflation pressure supporting the safety in their use.

Angioplasty, Balloon, Coronary↗
PubMed1997

Relationship between haemodynamics and morphology in pulmonary hypertension. A quantitative intravascular ultrasound study.

BACKGROUND: Intravascular ultrasound imaging of the pulmonary arteries has been demonstrated to be a reliable method of quantifying vessel diameter, luminal area and pulsatility. Simultaneous measurement of flow velocity and its response to vasodilators allows the relationship between morphology and functional compromise to be studied, especially endothelial dysfunction. METHODS: In 51 patients (mean age = 49.8 +/- 12.6 years, 17 female) we performed right heart catheterization and simultaneous intravascular ultrasound of pulmonary artery branches. The patients were divided in two groups: group 1 with normal pulmonary artery pressure and pulmonary vascular resistance, and group 2 with pulmonary hypertension (peak pulmonary artery pressure > 30 mmHg and/or mean pulmonary artery pressure > 20 mmHg). Vessel wall and lumen were studied using a 2.9 F intravascular ultrasound catheter with a 30 MHz phased array transducer. Measurement of blood flow velocity was accomplished by a Doppler flow wire (0.018 inch). The maximal flow change during acetylcholine infusion (adjusted to 10(-6); 10(-5), and 10(-4) M concentration in the blood vessel) was measured. RESULTS: There were no significant differences between groups 1 and 2 with respect to age (48.5 +/- 14.3 years vs 50.3 +/- 12.3 years; P = ns), gender (4 female/8 male vs 13 female/26 male; P = ns), luminal area of the vessel segment in which the intravascular ultrasound measurements were obtained (11.8 +/- 6.1 mm2 vs 16.7 +/- 14.3 mm2; P = ns), internal diameter (3.9 +/- 1.2 mm vs 4.2 +/- 1.7 mm; P = ns), and external diameter (6.1 +/- 1.3 mm vs 6.9 +/- 2.1 mm; P = ns). Cross-sectional images of the pulmonary artery wall demonstrated a single ring with high echodensity with a thin inner layer regarded as intima in group 1. In contrast, the majority of patients (n = 35/39) in group 2 demonstrated a thickening of the intimal layer and/or a disturbance of layering of the echogenic arterial wall. The relative wall thickness was higher in group 2 than in group 1 (22.5 +/- 10.4% vs 15.3 +/- 6.5%; P < 0.05). There were no significant correlations between pulmonary artery pressure and wall thickness pulmonary artery pressure and area change in the cardiac cycle, acetylcholine-dependent increase in pulmonary flow and morphological changes in the vessel wall. CONCLUSION: We conclude that intravascular ultrasound is capable of detecting morphological changes in the pulmonary vessel wall in pulmonary hypertension and that vessel wall hypertrophy of small pulmonary segment arteries, as detected by intravascular ultrasound, is not predictive of functional vasodilatory response of resistance vessels of the same vessel area.

Aged↗
PubMed1997

Respiratory muscle weakness and normal ventilatory drive in dilative cardiomyopathy.

BACKGROUND: In dilative cardiomyopathy several factors influence dyspnoea. Patients with chronic heart failure may demonstrate impairment of breathing pattern, ventilatory drive and respiratory muscle strength, as well as reduction of ventilatory efficiency. The purpose of this study was to evaluate whether dilative cardiomyopathy is accompanied by changes in breathing pattern, respiratory muscle weakness and ventilatory neural drive. METHODS: We investigated 47 patients (36 men, mean age = 47.8 +/- 11.2 years) with chronic heart failure due to dilative cardiomyopathy, and 30 healthy subjects (10 men, mean age = 35.4 +/- 11.7 years) served as controls. Patients and controls underwent evaluation of left ventricular ejection fraction by 2D echocardiography, spirometry, body plethysmography, mouth occlusion pressure and respiratory muscle strength, as well as by submaximal treadmill exercise testing with gas exchange measurements. The patients' results were compared to controls and predicted standard normal values, and evaluated for differences according to the degree of severity of functional impairment. RESULTS: Patients with dilative cardiomyopathy demonstrated a slight reduction in lung volumes (15% of the patients with obstructive and 15% with restrictive lung function pattern) and diffusion capacity (20.4 +/- 6.8 vs 15.4 +/- 6.7 ml.min-1.kPa-1; P < 0.01). In neural drive, as assessed by mouth occlusion pressure, there was no significant difference between patients and controls. There was a slight but significant reduction in respiratory muscle strength, as assessed by measuring maximal inspiratory pressure in patients with dilative cardiomyopathy (6.7 +/- 2.4 kPa vs 8.6 +/- 3.5 kPa; P < 0.01). The observed changes were more pronounced in the severe chronic heart failure patients (with a reduction in ventilatory efficiency) whereas no relationship among indices of cardiac or respiratory function was found. CONCLUSIONS: Patients with chronic heart failure due to dilative cardiomyopathy develop respiratory muscle weakness without changes in neural ventilatory drive, and slight changes in breathing pattern related to the severity of the disease.

Adult↗
PubMed1996

[Cost effectiveness of captopril after myocardial infarct; comment].

BACKGROUND: In Germany approximately 88,000 people died as a result of acute myocardial infarction and approximately 300,000 people suffered from acute myocardial infarction in 1992. These data demonstrate the socioeconomic impact of coronary disease. In the SAVE-(Survival-and-Ventricular-Enlargement) study, Pfeffer et al. demonstrated a reduction of morbidity and mortality due to therapy with captopril in patients after myocardial infarction. In a retrospective, incremental cost-effectiveness-analysis, from the perspective of German statutory insurance fund, the economic impact of captopril after myocardial infarction has been analysed. PATIENTS AND METHOD: The basis for the economic evaluation has been the double-blind, placebo-controlled, clinical SAVE-study which included 2,231 patients having left ventricular dysfunction after acute myocardial infarction. Additional data e.g. average number of hospital days or average costs for hospitalisation per day was taken from published national statistical sources. In the cost-effectiveness-analysis, inputs (monetary units) and outputs (non-monetary units) were identified and measured. The cost-effectiveness (costs per life-year gained) demonstrates a relation between the costs of captopril-treatment, costs for myocardial infarction and costs for leftventricular insuffiency and the clinical benefit e.g. life years gained. RESULTS: Initially costs in the captopril-group are 3.7 Mio DM higher as in the placebo-group. But these costs are partly compensated by the cost reductions in the captopril-group, compared to the placebo-group (2,162,901 DM) the reduction of myocardial infarction and DM 556,518 cost reduction due to fewer patients with left ventricular dysfunction. The clinical benefit of the captopril treatment equals 495 life years gained. The cost-effectiveness-ratio is 2,000 DM cost for life year gained. CONCLUSION: The treatment with captopril after acute myocardial infarction is not only a clinically efficacious treatment, but also cost-effective in patients after acute myocardial infarction.

Adult↗
PubMed1996

Exertional hyperpnea in patients with chronic heart failure is a reversible cause of exercise intolerance.

BACKGROUND: Hyperpnea in chronic heart failure occurs even in the absence of considerable impairment of lung function. It is caused by altered respiratory pattern with rapid shallow breathing and ventilation-perfusion mismatch, so far thought to be irreversible. OBJECTIVES: To test the underlying pathophysiologic disorders and the reversibility of this hyperpnea, i.e., the increased ventilatory response to exercise and its impact on exercise tolerance, 17 patients with chronic heart failure were evaluated before and 4 weeks after adjustment of heart failure therapy with diuretics and ACE inhibitors, and results were compared with normal volunteers. METHODS: Ventilatory response to exercise was measured during treadmill exercise by calculation of the slope of the linear relation between minute ventilation (VE) and carbon dioxide output (VCO2) and compared to NYHA class, oxygen consumption at the gas exchange anaerobic threshold (VO2 AT), maximal oxygen uptake (VO2 max) and ventilation of physiological dead space. RESULTS: VE vs VCO2 slope was related to severity of heart failure (NYHA class). Elevation of VE vs VCO2 slope was strongly correlated to elevated ventilation of physiologic dead space. Patients were divided into responders (significant decrease of VE vs VCO2 slope of at least 5 l/l I CO2) and nonresponders (decrease of VE vs VCO2 slope less than 5 I or increase). Responders revealed an increase of VO2 AT (7.4 +/- 2.6 to 11.7 +/- 2.1 ml O2/kg/min; p = 0.01) and VO2 max (11.2 +/- 2.8 to 17.4 +/- 5.3; p = 0.005), while nonresponders showed a non significant decrease of oxygen consumption (VO2 AT 9.6 +/- 3.7 to 9.0 +/- 3.7; peak VO2 14.6 +/- 6.1 to 14.4 +/- 6.4), despite adjusted heart failure therapy. CONCLUSION: Exercise hyperpnea in heart failure is mainly caused by ventilation of excess physiologic dead space and strongly contributes to severity of symptoms. Ventilatory response to exercise can be improved by adjustment of heart failure therapy in a considerable proportion of patients. Improvement is associated with an increase in aerobic capacity. Ventilation-perfusion mismatch is a major and modifiable factor determining exercise tolerance in patients with chronic heart failure.

Carbon Dioxide↗
PubMed1996

Angioscopic evaluation of atherosclerotic plaques: validation by histomorphologic analysis and association with stable and unstable coronary syndromes.

OBJECTIVES: We validated coronary angioscopic observations with histologic assessment of material removed by atherectomy. BACKGROUND: Up to now, angioscopic findings have been primarily descriptive, and the clinical significance still needs to be substantiated. The proposed Ermenoville classification is relevant but has not yet been validated by histomorphologic analysis. METHODS: We compared angioscopic findings in patients with different coronary syndromes and used atherosclerotic material retrieved by directional coronary atherectomy to validate the angioscopic observations. Coronary angioscopy was performed in 63 patients (56 men, 7 women) with stable (26 patients) and unstable angina (37 patients) before and after directional coronary atherectomy. The identity of atherectomized material was confirmed by ex vivo visualization with the angioscope and by postatherectomy angioscopy. Angioscopic and histologic findings could be compared in 44 of 63 patients. RESULTS: Angioscopic findings were grouped into gray-white and yellow lesions (gray-yellow, deep yellow, yellow-red or yellow-pink). We found that patients with unstable angina had predominantly yellow lesions (89%). In patients with stable angina, gray-white (43%) or yellow (57%) lesions were similarly distributed. Ruptured yellow plaques and red or pink thrombi were identified in 11% of patients with stable angina and 39% of patients with unstable or early postmyocardial infarction angina. Histologically, gray-white lesions represented fibrous plaque without degeneration in 64% and with degeneration in 36% of patients. Gray-yellow lesions were associated predominantly with degenerated plaque (64%) and, to a lesser extent, with fibrous plaque (14%) or atheroma (14%). Deep yellow and yellow-red lesions represented either atheroma (53%) or degenerated plaque (42%). CONCLUSIONS: Our study establishes a histomorphologic basis for classification and interpretation of angioscopic findings. Yellow plaque color is closely related to degenerated plaque or atheroma and is associated with unstable coronary syndromes.

Angina Pectoris↗
PubMed1996

The economics of cardiac failure.

Quality assurance and inclusion of prospective evaluation of costs of treatment in phase 3 and 4 pharmaceutical trials are becoming increasingly important. Not only high technology applications have to be investigated, but also relatively cheap but very common strategies for diagnostic work up and therapy. This may yield major savings. We are at the beginning of an era in which waste of resources may be reduced by scientific analysis with improvement in patient care and teaching achieved as a result.

Cost-Benefit Analysis↗