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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
PubMed2001

Passive containment and reverse remodeling by a novel textile cardiac support device.

BACKGROUND: Progressive remodeling and dilation of cardiac chambers is responsible in part for myocardial dysfunction in chronic heart failure. Preclinical studies with suitable animal models indicate that a passive cardiac constraint device can promote reverse remodeling, with improvement in cardiac function. We hypothesize that such a device could provide benefit for stable heart failure patients in New York Heart Association (NYHA) class II and III. METHODS AND RESULTS: From April 1999 to March 2000, 27 patients received Acorn's Cardiac Support Device (CSD) during an initial safety/feasibility study. In 11 patients, the only surgical measure was CSD placement. Most patients suffered from idiopathic cardiomyopathy; 4 were in NYHA class II, one was in class II/III, and 6 were in class III. All were stable on intensive medical treatment. The CSD, a textile polyester device, was fitted snugly around the heart during surgery. All patients survived surgery and recovered smoothly. Three months after surgery, 56% of patients were in NYHA class I, 33% were in class II, and 11% were in class II/III. Echocardiography showed an improvement in left ventricular ejection fraction from an average of 22% to 28% and 33% at 3 and 6 months, respectively. Simultaneously, the left ventricular end-diastolic dimension decreased from 74 mm to 68 mm and 65 mm, respectively. Mitral valve regurgitation (on a scale of 0 to 4+) decreased from 1.3 to 0.7 by 3 months. Quality-of-life indices correlated with the apparent reversal of ventricular remodeling. Preoperative cardiac medications remained virtually unchanged after implant. CONCLUSIONS: In the short- and intermediate-term, CSD implantation seems to ameliorate symptoms and improve cardiac and functional performance in heart failure patients. Worldwide randomized trials are currently underway.

Adult↗
PubMed2001

Torsades de pointes caused by Mibefradil.

We report a case of symptomatic Torsades de pointes due to QTc prolongation by Mibefradil, which potentially explains unexpected deaths related to this drug. Multiple episodes of Torsades de pointes were documented in a 76-year-old woman with significant QTc prolongation of 0.53 s. After discontinuation of Mibefradil QTc intervals normalized and no further ventricular tachyarrythmias were observed. We conclude that Mibefradil can cause QTc prolongation and life threatening ventricular dysrhythmias.

Aged↗
PubMed2000

Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure.

OBJECTIVES: We sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin. BACKGROUND: Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure. METHODS: A double-blind, placebo-controlled, randomized, multicenter, parallel-group study included 151 adult patients. Levosimendan was given as a 10-min intravenous bolus of 3, 6, 12, 24 or 36 microg/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 microg/kg/min, respectively. Dobutamine, for comparative purposes, was given as an open-label infusion (6 microg/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a > or =15% increase in stroke volume (SV) at 23 h to 24 h; 2) a > or =25% decrease in pulmonary capillary wedge pressure (PCWP) (and > or =4 mm Hg) at 23 h to 24 h; 3) a > or =40% increase in cardiac output (CO) (with change in heart rate [HR] <20%); 4) a > or =50% decrease in PCWP during two consecutive measurements. RESULTS: The response rate to levosimendan ranged from 50% at the lowest dose to 88% at the highest dose (compared with placebo 14%, dobutamine 70%). A dose-response relationship was demonstrated for levosimendan on increases in CO and SV, and reductions in PCWP during the infusion (for all, p< or =0.001). Headache (9%), nausea (5%) and hypotension (5%) were the most frequently reported adverse events at higher dosages. CONCLUSIONS: Dosing of levosimendan with a 10-min bolus of 6 to 24 microg/kg followed by an infusion of 0.05 to 0.2 microg/kg/min is well tolerated and leads to favorable hemodynamic effects.

Adult↗
PubMed2000

Impairment of ventilatory efficiency in heart failure: prognostic impact.

BACKGROUND: Impairment of ventilatory efficiency in congestive heart failure (CHF) correlates well with symptomatology and contributes importantly to dyspnea. METHODS AND RESULTS: We investigated 142 CHF patients (mean NYHA class, 2.6; mean maximum oxygen consumption [VO(2)max], 15.3 mL O(2) x kg(-1) x min(-1); mean left ventricular ejection fraction [LVEF], 27%). Patients were compared with 101 healthy control subjects. Cardiopulmonary exercise testing was performed, and ventilatory efficiency was defined as the slope of the linear relationship of V(CO(2)) and ventilation (VE). Results are presented in percent of age- and sex-adjusted mean values. Forty-four events (37 deaths and 7 instances of heart transplantation, cardiomyoplasty, or left ventricular assist device implantation) occurred. Among VO(2)max, NYHA class, LVEF, total lung capacity, and age, the most powerful predictor of event-free survival was the VE versus V(CO(2)) slope; patients with a slope </=130% of age- and sex-adjusted normal values had a significantly better 1-year event-free survival (88.3%) than patients with a slope >130% (54.7%; P<0.001). CONCLUSIONS: The VE versus V(CO(2)) slope is an excellent prognostic parameter. It is easier to obtain than parameters of maximal exercise capacity and is of higher prognostic importance than VO(2)max.

Adult↗
PubMed2000

Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension.

BACKGROUND: The continuous infusion of prostacyclin has been shown to improve exercise capacity and survival in patients with primary pulmonary hypertension (PPH). Inhalation of iloprost, a stable analog of prostacyclin, might be an alternative therapy for PPH, selectively acting on the pulmonary vascular bed through ventilation-matched alveolar deposition of the drug. We investigated the short-term effects of iloprost inhalation on exercise capacity and gas exchange in patients with PPH. METHODS AND RESULTS: In 11 patients with PPH, we performed 2 consecutive cardiopulmonary exercise tests before and after the inhalation of 17 microgram of iloprost. Patients had marked pulmonary hypertension (mean pulmonary artery pressure 65 mm Hg), and inhalation resulted in a decrease in pulmonary vascular resistance (1509 versus 1175 dyne. s(-1). cm(-5), P<0.05). Arterial blood gases remained unchanged (PaO(2) 69.3 versus 66.8 mm Hg; PaCO(2) 29.6 versus 28.8 mm Hg). Iloprost significantly (P<0.05) improved exercise duration (379 versus 438 seconds), peak oxygen uptake (12.8 versus 14.2 mL. kg(-1). min(-1)), VE-versus-V CO(2) slope (58 versus 51.4). CONCLUSIONS: The present data show that iloprost inhalation exerts pulmonary vasodilatation and improves symptoms and exercise capacity in patients with PPH. The data also suggest that iloprost inhalation is a suitable treatment for PPH. Whether these effects are maintained during long-term treatment and are paralleled by improvement in prognosis remains to be determined.

Administration, Inhalation↗
PubMed2000

Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group.

BACKGROUND: Inhaled aerosolized iloprost, a stable prostacyclin analogue, has been considered a selective pulmonary vasodilator in the management of pulmonary hypertension. OBJECTIVE: To assess the efficacy of inhaled iloprost in the treatment of life-threatening pulmonary hypertension. DESIGN: Open, uncontrolled, multicenter study. SETTING: Intensive care units and pulmonary hypertension clinics at six university hospitals in Germany. PATIENTS: 19 patients who had progressive right-heart failure despite receiving maximum conventional therapy (12 with primary pulmonary hypertension, 3 with pulmonary hypertension related to collagen vascular disease without lung fibrosis, and 4 with secondary pulmonary hypertension). INTERVENTION: Inhaled iloprost, 6 to 12 times daily (50 to 200 microg/d). MEASUREMENTS: Right-heart catheterization and distance walked in 6 minutes at baseline and after 3 months of therapy. RESULTS: During the first 3 months of therapy, New York Heart Association functional class improved in 8 patients and was unchanged in 7 patients. Four patients died, 3 of right-heart failure and 1 of sepsis. The acute hemodynamic response to inhaled iloprost was predominant pulmonary vasodilatation with little systemic effect at baseline and at 3 months (data available for 12 patients). Hemodynamic variables were improved at 3 months, and the distance walked in 6 minutes improved by 148 m (95% CI, 4.5 to 282 m; P = 0.048). Of the 15 patients who continued to use inhaled iloprost, 8 stopped: Four had lung transplantation, 1 switched to intravenous prostacyclin therapy, and 3 died. Seven patients are still receiving inhaled iloprost (mean +/-SD) duration of therapy, 536 +/- 309 days; mean dosage, 164 +/- 38 microg/d). CONCLUSIONS: Inhaled iloprost may offer a new therapeutic option for improvement of hemodynamics and physical function in patients with life-threatening pulmonary hypertension and progressive right-heart failure that is refractory to conventional therapy.

Administration, Inhalation↗
PubMed2000

[Iloprost as inhalational and intravenous long-term treatment of patients with primary pulmonary hypertension. Register of the Berlin Study Group for Pulmonary Hypertension]].

Follow-up data for 81 consecutive patients with primary pulmonary hypertension (PPH) and pulmonary hypertension related to connective tissue diseases or liver cirrhosis, entered into a multicenter registry in Berlin between 1/96 and 11/99, are described. At entry into the registry the diagnosis of PPH was known for 22 +/- 32 months. Hemodynamically, these patients were characterized by a right atrial pressure of 8.6 +/- 5 mmHg, a mean pulmonary arterial pressure of 58.9 +/- 17 mmHg, a cardiac index of 1.8 +/- 0.6 l/min/m2 and a pulmonary vascular resistance of 1574 +/- 787 dyn x s x cm-5. In about one third of the patients, a restrictive and/or obstructive pulmonary physiology was found while the majority showed signs compatible with small airway disease. Furthermore, diffusion abnormalities were found in about 65% of the patients. When added to conventional medical therapy the treatment with inhaled or continuously infused prostanoids represents a major improvement in the treatment of patients with PPH. Aerosolized iloprost therapy was started in 51 patients and was continued for 12 and 24 months in 20 and 6 patients, respectively. This therapy was well tolerated without any significant changes in pulmonary function or signs of toxicity. About 25% of these patients had to be switched to continuous intravenous therapy due to progressive clinical and hemodynamic deterioration. About two thirds of these "rescue patients" could be stabilized on intravenous therapy and discharged from the hospital. Based on the currently available evidence, the continuous infusion of prostanoids represents an important part of the standard therapy in the treatment of patients with PPH. These first long-term data on inhaled iloprost therapy in this patient group illustrate the potential value of this well-tolerated and effective treatment within the concept of a differentiated treatment plan for patients with PPH. However, the true importance of prostanoid inhalation in comparison to continuous intravenous therapy in PPH remains to be determined in randomized controlled trials.

Administration, Inhalation↗
PubMed2000

Oxidative stress in the human heart is associated with changes in the antioxidative defense as shown after heart transplantation.

The study was designed to demonstrate--for the first time in humans--that oxidative stress in the heart indicated by lipid peroxidation is associated with time-dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial biopsies (taken between the fifth day and 6 years after transplantation) of 31 heart transplant recipients who were suspected of suffering from increased formation of oxygen radicals in the allograft. The levels of lipid peroxides (LPO), glutathione peroxidase (GSH-Px), total-, copper/zinc- and manganese superoxide dismutase (t-SOD, CuZnSOD, MnSOD) were compared in 3 post-transplantation periods (5-90 d vs. 91-365 d vs. >1 y). Significantly increased LPO levels were found (0.27+/-0.04 vs. 0. 13+/-0.02 vs. 0.27+/-0.04 nmol/mg protein) in the first and third period. Increased activities of GSH-Px (39.8+/-3.8 vs. 30.2+/-4.1 vs. 76.7+/-6.5 mU/mg protein), t-SOD (1.57+/-0.10 vs. 1.30+/-0.14 vs. 2.44+/-0.23 U/mg protein) and CuZnSOD (1.09+/-0.08 vs. 0.93+/-0.13 vs. 2.05+/-0.21 U/mg protein) occurred only in the third period. For calculation of time courses more precisely, the single data with respect to time were analyzed with a curve fitting program. Except for the first period, the allograft LPO and GSH-Px levels rose for up to 6 years after transplantation. However, the t-SOD and CuZnSOD activities switched from increase to decrease in the third period. The study provided indication for: first, the potency of the human heart to time-limited increase of the enzymatic antioxidative defense, and secondly, the inability of human heart allografts--despite this adaptation--for complete prevention of myocardial oxidative stress.

Adult↗
PubMed2000

Relationship between impaired pulmonary diffusion and cardiopulmonary exercise capacity after heart transplantation.

STUDY OBJECTIVES: Diffusion impairment and reduced performance in cardiopulmonary exercise testing (CPX) have been found in patients after heart transplantation. The pathogenesis of these abnormalities is unclear. In particular, the contribution of pulmonary interstitial changes has not yet been verified. DESIGN: We analyzed pulmonary function tests, high-resolution CT (HRCT), echocardiography, left heart catheterization, and CPX in transplanted patients. PATIENTS: Forty long-term survivors were studied at a median of 47 months (range, 12 to 89 months) after heart transplantation. RESULTS: Diffusion was impaired in 40% (transfer factor for carbon monoxide) or 82.5% (carbon monoxide transfer coefficient) of the patients. Diffusion impairment was caused by a decreased diffusing capacity of the alveolar capillary membrane in 89% and/or by a decreased blood volume of the alveolar capillaries in 46% of cases. In five patients (12.5%), CT revealed interstitial lung changes. These patients did not have different values of diffusion capacity. Maximal oxygen uptake and ventilatory efficiency during exercise (minute ventilation/carbon dioxide output slope) were impaired in 92% and 46% of the cases, respectively. CONCLUSIONS: Our data show that the diffusion abnormalities are caused by an impaired diffusion status of the alveolar capillary membrane. Interstitial changes detectable in HRCT were found not to be involved in this process. The reduced performance in CPX in our long-term survivors is caused by pulmonary perfusion abnormalities and low tidal volume, which is due to the deconditioning of respiratory muscle, rather than by interstitial changes or diffusion abnormalities.

Adult↗
PubMed1999

[Spiroergometry in diagnosis of mitochondrial diseases].

Cardiopulmonary exercise testing (CPX) is a non-invasive method of recording quantitative data from gas exchange and ventilation for the evaluation of oxidative metabolism at rest and during exercise. Determination of oxygen uptake (VO2) and carbon dioxide output (VCO2) describes the activity of anaerobic vs aerobic metabolism. An incremental exercise test measuring gas exchange, ventilation and lactate release was performed in healthy volunteers and in patients suffering from mitochondrial disorders. At rest as well as during exercise patients with mitochondrial disorders differ from healthy subjects with regard to gas exchange and ventilation parameters. During exercise, the decreased oxygen utilization of skeletal muscle and early activation of anaerobic metabolism in these patients are mirrored by a reduced anaerobic threshold, reduced maximal oxygen uptake and reduced oxygen pulse. Our study shows that CPX is a sensitive and practical clinical screening method of investigating mitochondrial disorders.

Adolescent↗
PubMed1999

[Therapy of acute heart failure, medicamentous strategy].

The leading pathophysiology of acute heart failure and cardiogenic shock is acute or subacute myocardial infarction. Reperfusion of the occluded coronary vessel accompanied by adequate support of cardiac function via assist systems, preferentially the intraaortic balloon counterpulsation, is the therapy of choice. Adjustment of preload (high pulmonary capillary pressure in-acute myocardial infarction with small heart, low pulmonary capillary wedge pressure in patients with large ventricles and chronic heart failure, high central venous pressure in patients with right heart failure, and right ventricle myocardial infarction) and afterload (peripheral arterial vasodilatation, recommended systolic arterial pressure 80-90 mm Hg) but not maximization of cardiac output play an important role. Positive inotropic drugs should be considered when these strategies fail. In acute right heart failure in pulmonary hypertension, a preferential pulmonary vasodilatation with intravenous or inhalative prostaglandins or inhalative NO are of utmost importance. Systemic hypotension is not a contraindication in this pathophysiology.

Cardiotonic Agents↗
PubMed1999

Acetylcholine but not sodium nitroprusside exerts vasodilation in pulmonary hypertension secondary to chronic congestive heart failure.

BACKGROUND: Reduced endothelium-dependent vasodilation contributes to the development of pulmonary hypertension in chronic congestive heart failure (CHF). We investigated pulmonary endothelium-dependent and independent vasodilation in patients with CHF. METHODS: We studied 42 patients with CHF (age 55 +/- 10, NYHA Classes II-III, left ventricular ejection fraction 27 +/- 10%, mean PAP 29 +/- 12 mmHg). The endothelial vasodilator capacity of pulmonary resistance vessels was assessed by the infusion of acetylcholine into a pulmonary artery branch while measuring the blood flow velocity with a Doppler flow wire. For comparison endothelium-independent vasodilation was measured with the response to sodium nitroprusside. The conductance vessel diameter (4.4 +/- 0.2 mm) was determined by intravascular ultrasound. Acetylcholine was administered at concentrations of 10(-6) to 10(-4) mol/l, sodium nitroprusside was administered at concentrations of 0.125 and 0.25 microg/kg per min. The effects on conductance vessel diameter were investigated in 12 patients by the measurement of diameter and flow velocity following the administration of acetylcholine and sodium nitroprusside. RESULTS: Acetylcholine markedly increased blood flow velocity (+39 +/- 7% at 10(-4) mol/l; p < .05). This correlated with the baseline PAP (r = 0.58; p < .05) and pulmonary vascular resistance (r = 0.58; p < .05). Sodium nitroprusside caused a small increase in the flow velocity (5 +/- 2% at 0.125, 12 +/- 4% at 0.25 microg/kg per minute; p < .05) that was accompanied by systemic vasodilation. The conductance vessel diameter was unchanged after acetylcholine was administered and was only marginally decreased after the administration of sodium nitroprusside. CONCLUSIONS: In CHF acetylcholine reveals preserved receptor-mediated endothelial vasodilation, that is positively correlated to pulmonary hypertension, and cannot be reproduced by sodium nitroprusside.

Acetylcholine↗
PubMed1999

Pulmonary artery stenosis 5 years after single lung transplantation in primary pulmonary hypertension.

This is a case report about a 56-year-old female patient with primary pulmonary hypertension who underwent single, right lung transplantation. Five years postoperatively she developed signs of right heart failure. History and physical examination suggested pulmonary artery stenosis. Diagnosis was confirmed by pulmonary angiography. Percutaneous placement of a balloon expandable stent normalized pulmonary artery pressure.

Blood Pressure↗
PubMed1999

Achieving appropriate endpoints in heart failure trials: the PRIME-II protocol. The Second Perspective Randomised study of Ibopamine on Mortality and Efficacy.

Many clinical trials unintentionally include patients with a low risk of the trial endpoints. PRIME II (The Second Perspective Randomised study of Ibopamine on Mortality and Efficacy) was a large international randomised double blind trial comparing the addition of ibopamine or placebo to the therapy of patients with advanced heart failure. The trial was stopped prematurely because ibopamine was associated with an increased fatality rate, but the protocol achieved its objective of including high-risk patients. Here we describe the protocol details that enabled patients with the desired degree of risk to be included. We also amplify our definition of mode of death. The PRIME II protocol was designed with the intention that patients in the placebo group would have an annual fatality rate of 20%. Since the study was to be conducted in some 200 centres in 13 European countries, the inclusion criteria had to be simple and flexible, allowing for different clinical practice. The inclusion criteria, together with the use of simple investigations (which did not have to include angiographic or radionuclide ventriculography) are described. The annual fatality rate in the placebo group was just over 20%. Six categories of mode of death were used, but while they were reasonably easy to apply they did not reveal the reason for the unexpected adverse effect of ibopamine. The inclusion and exclusion criteria used for PRIME II, and the definitions of mode of death, were effective. The PRIME II protocol can be used as a model for future heart failure studies.

Clinical Protocols↗
PubMed1999

Management of patients with acute myocardial infarction at five academic medical centers: clinical characteristics, resource utilization, and outcome.

BACKGROUND: Although variability in management of cardiovascular syndromes has been demonstrated among regions, the extent to which variability exists among academic medical centers in different countries in uncertain. METHODS: This retrospective cohort study includes data on consecutive patients (n = 694) with acute myocardial infarction who were admitted to five teaching hospitals from different countries (84, Brigham and Women's Hospital, USA; 97, Iizuka Hospital, Japan; 64, Hospital de Clinicas de Porto Alegre, Brazil; 62, Universitätsklinikum Charité, Germany; and 387, Hôpital Cantonal Universitaire de Genève, Switzerland) during a one-year period. Data were collected via chart review on clinical characteristics, rates of diagnostic and therapeutic interventions, complications and mortality, length of stay, and one-year follow-up outcomes. RESULTS: Patients' clinical characteristics varied among these institutions, with the lowest prevalence of antero-septal myocardial infarction at the US hospital. The US hospital had the lowest rate of use of thrombolytic therapy and did not have the highest rate for any invasive procedure. Average length of stay ranged from 7.7 +/- 4.3 days in the US hospital to 47.2 +/- 27.9 days in the Japanese hospital. There were no differences in one-year mortality among the four institutions (4% to 8%, P = 0.881) for which data were available. CONCLUSIONS: In this nonrandom sample of academic medical centers, the use of aggressive therapies for acute myocardial infarction was at least as common at non-US as US hospitals. Length of stay was much shorter at the US hospital. Despite these variations in management, evidence for differences in outcomes at one year were not detected.

Academic Medical Centers↗
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↗