Christiana Mira Schannwell's research while affiliated with Heinrich-Heine-Universität Düsseldorf and other places

Despite accumulated evidence that intracoronary bone marrow cell (BMC) therapy may be beneficial in acute myocardial infarction, there are only limited data available on the effectiveness of BMC's in chronic heart failure. The aim of this study was to quantitatively investigate ventricular haemodynamics, geometry, and contractility as well as the long-term clinical outcome of BMC treated patients with reduced left ventricular ejection fraction (LVEF) due to chronic ischaemic cardiomyopathy. Patients with chronic heart failure (n = 391 LVEF <or=35%) due to ischaemic cardiomyopathy were enrolled in the present study. Of these, 191 patients (mean NYHA class 3.22) underwent intracoronary BMC therapy. The control group (mean NYHA class 3.06) consisted of 200 patients with comparable LVEF. Assessments of haemodynamics at rest and exercise, quantitative ventriculography, spiroergometry, 24 h Holter ECG, late potentials, and heart rate variability were analysed. Over 3 months to 5 years after intracoronary BMC therapy there was a significant improvement in haemodynamics (e.g. LVEF, cardiac index), exercise capacity, oxygen uptake, and LV contractility. Importantly, there was a significant decrease in long-term mortality in the BMC treated patients compared with the control group. Intracoronary BMC therapy improves ventricular performance, quality of life and survival in patients with heart failure. These effects were present when BMC were administered in addition to standard therapeutic regimes. No side effects were observed.

The aim of this study was to investigate the quantitative amount of improvement of ventricular hemodynamic status, geometry, and contractility as well as the long-term clinical outcome of cell-treated patients after acute myocardial infarction (AMI). Animal experiments as well as clinical studies have demonstrated that autologous bone marrow cell (BMC) transplantation might improve ventricular function and prevent remodeling. Sixty-two patients underwent intracoronary autologous BMC transplantation 7 +/- 2 days after AMI. Cells were infused directly into the infarct-related artery. The control group consisted of 62 patients with comparable left ventricular (LV) ejection fraction (EF) and diagnosis. All patients had several examinations (e.g., coronary angiography, right heart catheterization, biplane left ventriculography, electrocardiogram [ECG] at rest and exercise, echocardiography, late potential [LP], heart rate variability [HRV], and 24-h Holter ECG). The therapeutic follow-up was performed 3, 12, and 60 months after BMC therapy. Three months after BMC therapy there was significant improvement of EF and stroke volume index. The infarct size was significantly reduced by 8%. Contraction velocities (lengths/second, volumes/second) increased significantly and the slope of the ventricular function curve (systolic pressure/end-systolic volume) became steeper. There was significant improvement of contractility in the infarct zone, as evidenced by a 31% increase of LV velocity of shortening (VCF), preferably in the border zone of the infarct zone. In contrast, the noninfarcted area showed no difference in VCF before and after BMC therapy. Furthermore, decreases of abnormal HRV, LP, and ectopic beats were documented after BMC therapy. Twelve and 60 months after BMC therapy the parameters of contractility, hemodynamic status, and geometry of the LV were stable. The exercise capacity of treated patients was significantly augmented, and the mortality was significantly reduced in comparison with the control group. BMC therapy leads to significant and longstanding improvements of LV performance as well as quality of life and mortality of patients after AMI. After BMC therapy, no side effects were observed, showing that BMC therapy is safe.

Die selektive intrakoronare Transplantation von autologen mononukleären Knochenmarkzellen (chronischer Infarkt: 10⁹ Millionen Zellen) stellt ein neuartiges und effektives Therapieverfahren dar. Zusätzlich zur Koronarintervention (PTCA + Stent), die zur Gefäßrestitution führt, zielt die Zelltherapie darauf ab, geschädigtes Myokard im Sinne einer Kausaltherapie wiederherzustellen. Bei chronischer koronarer Herzkrankheit (im Mittel 108 Monate nach Infarkt) kommt es zur signifikanten Verbesserung der Pumpfunktion und Kontraktilität sowie parallel zur Infarktgrößenabnahme, zur Zunahme der myokardialen Glukoseaufnahme und der Belastungstoleranz und des subjektiven Wohlbefindens. Die Effektivität der Knochenmarkzelltransplantation beruht nach dem derzeitigen Kenntnisstand auf vier unterschiedlichen Mechanismen: Zell-Transdifferenzierung, Zellfusion, zytokinvermittelte Myozyten-Vermehrung und Mobilisierung intrinsischer kardialer Stammzellen. Die kombinierte intraarterielle und intramuskuläre Transplantation von autologen, adulten Knochenmarkstammzellen könnte eine klinisch einfache und sichere Therapieoption für Patienten mit schwerer pAVK darstellen. Sie bewirkt eine signifikante Steigerung der Perfusionsindizes. Bisher sind keine Komplikationen/Nebenwirkungen bekannt. Bezüglich der Transplantation autologer Knochenmarkzellen bestehen keine ethischen Bedenken.

Heart failure is a dangerous disease with an increasing frequency. Although conventional drug therapy may delay remodeling, there is no basic therapeutic regime available for preventing or even reversing this process. Several preclinical as well as clinical trials have shown that transplantation of autologous bone marrow cells improved cardiac function after myocardial infarction and chronic heart disease (CAD). We investigated the effects of intracoronary (ic) autologous stem cell transplantation (STX) at patients with non-ischemic dilated cardiomyopathy (DCM). Methods: A total of 10 patients with DCM were included in this study (group I). The control group also consists of 10 age and sex-matched patients with comparable ejection fraction (group II). CAD and myocarditis were excluded. All patients of group I received an ic autologous STX with mononuclear cells. Cell transplantation was performed via the ic administration route. All cells were infused directly into the dominant coronary vessel. To achieve a maximal ischemic stimulus all patients received Dobutamine intravenously and Dipipyridamol by ic application. All 20 patients were re-investigated after 3 months. Results: Three months after ic STX, the global left ventricular ejection fraction increased in patients from 18 ± 1 up to 26 ± 3% (p < 0.01). In parallel the physical ability (functional capacity) rose from 25 to 75 watt (p < 0.01). In addition, we found an improvement of maximum oxygen uptake under stress from 1236 ± 217 up to 1473 ± 198 ml/min (p < 0.01). Furthermore we documented a reduction of arrythmia. An unchanged or even impaired left ventricular function was not observed in any patient of group I. In the control group (group II) no significant changes were documented. No side effects of ic autologous STX were found, particularly no arrythmias, no heart insufficiency, no dyspnoea and no palpitations. Conclusion: These results show that transplantation of autologous bone marrow cells, as well as the ic approach, represents a novel and effective therapeutic procedure for the therapy of DCM. For this method of therapy, no ethical problems exist, and no side effects were observed. However, further experimental studies and controlled prospective clinical trials have to follow.

Continuous positive airway pressure (CPAP) may be a useful adjunct in patients with congestive heart failure. To evaluate the relationship between left ventricular geometry and hemodynamic response to CPAP. Right heart catheter studies were performed in 26 patients before, during and after application of CPAP (8 cm H(2)O) over 15 min. Response to therapy was defined as an increase in stroke volume using CPAP. Cardiac output decreased from 6.9 +/- 1.9 to 6.2 +/- 1.4 liters/min (p = 0.01) with a slight increase after cessation of CPAP (not significant). There was no significant change in stroke volume (92 +/- 34 vs. 90 +/- 31 ml, p = 0.584) or pulmonary capillary wedge pressure (14.7 +/- 7.0 vs. 14.2 +/- 6.5 mm Hg, p = 0.26). There was a correlation between hemodynamic effects of CPAP therapy and left ventricular end-diastolic volume (r = 0.515, p = 0.01), mass-volume ratio (r = -0.41, p = 0.04) and pulmonary capillary wedge pressure (r = 0.654, p = 0.001) at baseline. Half the patients (n = 13) were categorized as responders with an average increase in stroke volume of 11.5 +/- 2.1%. Responders showed significantly higher left ventricular end-diastolic volume, pulmonary capillary wedge pressure and lower mass-volume ratio. Patients with high pulmonary capillary wedge pressure, elevated end-diastolic volumes and a low left ventricular mass-volume ratio might profit from CPAP therapy.

The effect of intracoronary administration of autologous bone marrow cells on autonomic modulation of heart rate has not yet been demonstrated. Therefore, we investigated different parameters of heart rate variability (HRV) in 46 patients without (n=23) or with (n=23) intracoronary stem cell therapy after transmural myocardial infarction. After three to twelve months of follow up, patients receiving stem cells showed a significant increase of HRV parameters that have been linked to cardiovascular prognosis.

The internal thoracic artery is an established arterial graft for myocardial revascularization. It never had been investigated, whether there are functional differences in this vessel between patients with or without coronary artery disease. We investigated the left internal thoracic artery of 28 patients (15 with and 13 without coronary artery disease) with a duplex-system at rest and with a handgrip exercise. Concerning the measured flow velocities at rest there was only a significant difference between the diastolic mean and peak velocity between the two groups, the other investigated parameters demonstrate no significant difference. The peak diastolic and the mean diastolic velocity was less in patients with coronary artery disease during the handgrip-test. The flow reserve was decreased in patients with coronary artery disease (12.6+/-24.0% vs. 32.3+/-30.9%, P < 0.05). We demonstrated, that patients with coronary artery disease have a higher peripheral resistance and a lower diastolic velocity of the internal thoracic artery during stress testing. This corresponds to a disturbed vasomotion and may be an early marker of arteriosclerosis.

Cardiovascular disease remains the leading cause of mortality for women and men in developed countries. Although coronary artery disease is the major cause of morbidity and mortality in women, coronary heart disease in women is still clinically underestimated. Although the incidence of coronary heart disease increases with age in women, the clinical presentation of the disease lags 10 years behind that in men. Unfortunately, the routinely available noninvasive tests used to screen the presence of coronary artery disease have been relatively insensitive and nonspecific for women. However, recent advances in device application, adjunctive therapies and surgical techniques suggest that coronary revascularization strategies are safe and effective for women and men.

Cardiac disease is the most common cause of death in patients with endstage renal disease. It was assumed that the high rate of cardiovascular mortality was based on accelerated atherosclerosis. Recently published articles, however, demonstrated that only 30-50% of all cardiac deaths in patients with uremia was due to myocardial infarction. On the other hand 30-40% of all patients with renal insufficiency, angina pectoris and documented ischemia have normal coronary arteries. Therefore, it is suggested that in patients with chronic uremia apart from accelerated atherosclerosis further abnormalities of the heart lead to myocardial ischemia. Recently published papers report functional and structural changes, which affect myocardial perfusion reserve. These structural changes include left ventricular hypertrophy, interstitial myocardial fibrosis, and microvascular disease.