Stephan Steiner

Altered Blood Rheology in Obstructive Sleep Apnea as a Mediator of Cardiovascular Risk

Background: Cardiovascular complications are common in patients with obstructive sleep apnea (OSA). Blood rheology is a major determent of coagulation and an established risk factor for cardiovascular events. Since nocturnal hypoxemia could influence parameters of blood rheology, we hypothesized that OSA alters blood rheology independent of other cardiovascular risk factors. Methods: One hundred and ten consecutive patients admitted to the sleep laboratory were included. The association of plasma fibrinogen and viscosity (as parameters of blood rheology) with OSA was evaluated. Results: One hundred and ten patients aged 61.4 ± 10.1 years (body mass index 28.4 ± 4.1 kg/m2) were included. OSA was confirmed in 63 patients (57.2%) with an apnea-hypopnea index (AHI) of 28.7 ± 14.9 events/hour. Patients with OSA showed higher levels of plasma viscosity (1.36 ± 0.09 vs. 1.31 ± 0.08 mPas, p = 0.005). Nevertheless, hypertensive apneics have even higher levels of plasma viscosity than nonapneics (1.38 ± 0.091 vs. 1.32 ± 0.028 mPas, p = 0.018). Similar results were found in patients with coronary artery disease, where OSA was associated with elevated plasma viscosity (1.36 ± 0.076 vs. 1.31 ± 0.081 mPas, p = 0.007). Plasma fibrinogen was correlated with nocturnal minimal oxygen saturation (r = –0275, p = 0.0036) and AHI (r = 0.297, p = 0.001). OSA was associated with higher plasma fibrinogen (353 ± 83 vs. 317 ± 62 mg/dl, p = 0.015). These differences persist with control for cardiovascular risk factors. Conclusions: Patients with OSA have elevated morning fibrinogen levels and a higher plasma viscosity, which correlate positively with indices of sleep apnea severity. These changes in blood rheology are independent of cardiovascular risk factors, and therefore, might be specific mechanisms of OSA. This supports the pathophysiological concept that sleep apnea is a cardiovascular risk factor.

Occurrence of Coronary Collateral Vessels in Patients With Sleep Apnea and Total Coronary Occlusion

BACKGROUND Obstructive sleep apnea (OSA) is thought to act as a coronary risk factor. There is emerging evidence that intermittent phases of hypoxia might contribute to alterations of the cardiovascular system. We hypothesized that OSA syndrome (OSAS) might be accompanied by an increased coronary collateral vessel (CCV) development in patients with total coronary occlusion. METHODS Thirty-four patients with total coronary occlusions were classified according to the apnea-hypopnea index (AHI) (OSAS: AHI > 10/h; non-OSAS: AHI < 10/h). CCVs were scored by visual analysis and were analyzed according to the Cohen and Rentrop grading system. RESULTS There was no significant discrepancy between the groups concerning the prevalence of age, gender, the presence of hypertension, smoking, or diabetes mellitus. There was no difference in left ventricular systolic function (ejection fraction 53% +/- 20% vs 61% +/- 20%, P = .29) or left ventricular end-diastolic pressure (22.6 +/- 8.5 mm Hg vs 18.5 +/- 7.7 mm Hg, P = .41). OSAS showed a higher Rentrop score compared with non-OSAS (1.61 +/- 1.2 vs 2.4 +/- 0.7, P = .02). CONCLUSIONS These findings suggest that CCV development is augmented in patients with OSA.

Impact of obstructive sleep apnea on the occurrence of restenosis after elective percutaneous coronary intervention in ischemic heart disease

RationaleThere is growing evidence that obstructive sleep apnea is associated with coronary artery disease. However, there are no data on the course of coronary stenosis after percutaneous coronary intervention in patients with obstructive sleep apnea.ObjectivesTo determine whether sleep apnea is associated with increased late lumen loss and restenosis after percutaneous coronary intervention.Methods78 patients with coronary artery disease who underwent elective percutaneous coronary intervention were divided in 2 groups: 43 patients with an apnea hypopnea – Index < 10/h (group I) and 35 pt. with obstructive sleep apnea and an AHI > 10/h (group II). Late lumen loss, a marker of restenosis, was determined using quantitative coronary angiography after 6.9 ± 3.1 months.Main resultsAngiographic restenosis (>50% luminal diameter), was present in 6 (14%) of group I and in 9 (25%) of group II (p = 0.11). Late lumen loss was significant higher in pt. with an AHI > 10/h (0.7 ± 0.69 mm vs. 0.38 ± 0.37 mm, p = 0.01). Among these 35 patients, 21(60%) used their CPAP devices regularly. There was a marginally lower late lumen loss in treated patients, nevertheless, this difference did not reach statistical significance (0.57 ± 0.47 mm vs. 0.99 ± 0.86 mm, p = 0.08). There was no difference in late lumen loss between treated patients and the group I (p = 0.206).ConclusionIn summary, patients with OSA and coronary artery disease have a higher degree of late lumen loss, which is a marker of restenosis and vessel remodeling after elective percutaneous intervention.

Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction

Autologous bone marrow cell transplantation (BMCs‐Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs‐Tx on the mobilization of bone marrow–derived circulating progenitor cells (BM‐CPCs) in patients with acute myocardial infarction (AMI). Sixty‐two patients with AMI were randomized to either freshly isolated BMCs‐Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45+‐ and CD133/45+‐circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs‐Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45+ and CD133/45+ BM‐CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45+: P < 0.001, CD133/45+: P < 0.001). Moreover, this significant mobilization of BM‐CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45+ and CD133/45+ BM‐CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45+ and CD133/45+ BM‐CPCs in PB and this might increase the regenerative potency after AMI.

Factors influencing spontaneous mobilization of CD34+ and CD133+ progenitor cells after myocardial infarction.

Background  Bone marrow‐derived circulating progenitor cells (BM‐CPCs) are mobilized into adult peripheral blood (PB) during acute myocardial infarction (AMI) and may contribute to the regeneration of infarcted myocardium. The purpose of the present study is to determine whether mobilization of BM‐CPCs into PB depends on cardiovascular risk factors (CVRFs), age of patients, infarct associated inflammatory markers, and left ventricular function after AMI.

Prevalence of Paroxysmal Atrial Fibrillation Depending on the Regression of Left Ventricular Hypertrophy in Arterial Hypertension

Arterial hypertension (HTN) represents one of the major causes of atrial fibrillation, a cardiac arrhythmia with high prevalence and comorbidity. The aim of this study was to investigate whether paroxysmal atrial fibrillation can be treated by the regression of left ventricular hypertrophy achieved by antihypertensive therapy. Included in the present study were 104 patients who had had HTN for more than 1 year. None of them suffered from coronary heart disease. All patients were investigated by 24-h Holter ECG and echocardiography at baseline and after a mean of 24 months. Patients were divided into two groups: group A consisted of those (53.8%) who showed a regression of the left ventricular muscle mass index (LVMMI) during the follow-up (154.9±5.1 vs. 123.5±2.8 g/m2), and group B those (45.2%) who showed a progression of LVMMI (122.2±3.2 vs. 143.2±3.2 g/m2). In group A the prevalence of atrial fibrillation decreased from 12.5% to 1.8% (p<0.05), while it was increased in group B from 8.5% to 17.0%. The left atrial diameter was reduced following antihypertensive therapy in group A from 39.1±5.3 mm to 37.4±4.6 mm (p<0.01) and increased in group B from 37.0±0.7 mm to 39.0±0.9 mm (p<0.01). We conclude that a regression of the left ventricular muscle mass leads to a reduction of left atrial diameter and consecutively to a decrease in the prevalence of intermittent atrial fibrillation. This may be explained by a better left ventricular diastolic function following decreased vascular and extravascular resistance of the coronary arteries. This relation shows the benefits of causal antihypertensive therapy for the treatment of paroxysmal atrial fibrillation.

Improved Mobilization of the CD34+ and CD133+ Bone Marrow-Derived Circulating Progenitor Cells by Freshly Isolated Intracoronary Bone Marrow Cell Transplantation in Patients with Ischemic Heart Disease

Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45(+) and CD133/45(+) CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD.

Left Ventricular Response to Continuous Positive Airway Pressure: Role of Left Ventricular Geometry

Background: Continuous positive airway pressure (CPAP) may be a useful adjunct in patients with congestive heart failure. Objectives: To evaluate the relationship between left ventricular geometry and hemodynamic response to CPAP. Methods: Right heart catheter studies were performed in 26 patients before, during and after application of CPAP (8 cm H2O) over 15 min. Response to therapy was defined as an increase in stroke volume using CPAP. Results: 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. Conclusion: Patients with high pulmonary capillary wedge pressure, elevated end-diastolic volumes and a low left ventricular mass-volume ratio might profit from CPAP therapy.

Hypertensive mikrovaskuläre Erkrankung

ZusammenfassungDie arterielle Hypertonie stellt einen relevanten kardiovaskulären Risikofaktor dar und führt sowohl zu vaskulären als auch zu myokardialen Manifestationen am Herzen. Besondere Bedeutung kommt der hypertensiv bedingten koronaren Mikroangiopathie zu. Das klinische Bild des Patienten mit hypertensiv bedingter koronarer Mikroangiopathie wird durch die Koronarinsuffizienz mit typischer Angina pectoris, aber auch Herzinsuffizienz (systolische und diastolische Dysfunktion) und Herzrhythmusstörungen bestimmt.Die Diagnose der hypertensiven mikrovaskulären Erkrankung kann durch nichtinvasive und invasive Verfahren vermutet werden; eine Sicherung der Diagnose ist nur durch Bestimmung der koronaren Flussreserve möglich.Primäres Therapieziel ist neben der effektiven Blutdrucknormalisierung die Rückführung der hypertensiv bedingten kardialen Veränderungen durch die Einleitung spezifischer Therapiemaßnahmen.AbstractArterial hypertension is a major cardiovascular risk factor and leads to vascular as well as to myocardial manifestations. Particularly hypertensive microvascular disease is of great importance. Major clinical manifestations of hypertensive heart disease are symptoms of coronary insufficiency with typical angina pectoris, but also heart failure (systolic or diastolic dysfunction) and arrhythmia.Different non-invasive and invasive procedures are available for screening. For ultimate quantitative assessment of the coronary reserve, invasive procedures are still required. Beside lowering blood pressure primary therapeutic target is to reverse cardiac manifestations of arterial hypertension using specific therapeutic algorithms.

Determinanten des paroxysmalen Vorhofflimmerns bei Patienten mit arterieller Hypertonie

Introduction: Atrial fibrillation represents an important arrhythmia, in particular in patients with arterial hypertension. Hitherto, the connection between paroxysmal atrial fibrillation, left atrial size and left ventricular muscle mass has not been investigated sufficiently. In the present study, determinants of paroxysmal atrial fibrillation in patients with arterial hypertension were evaluated. Methods: 104 consecutive patients were enrolled into this study. All of them suffered from arterial hypertension for more than one year. Persistent or permanent atrial fibrillation was not documented. In all of these patients, clinical, echocardiographic and rhythmologic variables were evaluated. Results: In 10.3% of the patients, paroxysmal atrial fibrillation was found. These patients showed a significantly larger left atrium (43.3±6.7 vs 37.5±4.9mm, p<0.001), a significantly higher muscle mass of the left ventricle (152.38±43.57 vs 134.41±27.19g/m2, p<0.01) and significantly more frequent a mild mitral regurgitation (38.1 vs 28.6%, p<0.01). The multivariate regression analysis revealed as independent factors for paroxysmal atrial fibrillation the size of the left atrium and the presence of mild mitral regurgitation. Independent factors for an enlarged left atrium were mitral insufficiency and left ventricular muscle mass. Conclusion: This study shows that paroxysmal atrial fibrillation in aterial hypertension is based on the left atrial size, and left atrial size on left ventricular muscle mass. Therefore, these results should lead to a causal therapy for treatment of paroxysmal atrial fibrillation in these patients. Einleitung: Vorhofflimmern stellt eine insbesondere für Hypertoniker klinisch bedeutsame Arrhythmie dar. Der Zusammenhang zwischen paroxysmalem Vorhofflimmern, linksatrialer Vorhofgröße und ventrikulärer Muskelmasse ist bisher allerdings noch unzureichend untersucht. In der vorliegenden Studie sollten Determinanten des paroxysmalen Vorhofflimmerns bei Patienten mit arterieller Hypertonie erfasst werden. Methoden: In diese Studie wurden 104 Patienten eingeschlossen. Alle hatten eine über ein Jahr bestehende arterielle Hypertonie. Persistierendes oder permanentes Vorhofflimmern bestand nicht. Bei diesen wurden neben klinischen die echokardiographischen und rhythmologischen (24-Stunden-EKG) Daten erfasst. Ergebnisse: Insgesamt wurde in 10,3% der Fälle paroxysmales Vorhofflimmern festgestellt. Diese Patienten wiesen einen signifikant größeren linken Vorhof auf (43,3±6,7 vs. 37,5±4,9mm, p<0,001), daneben eine signifikant höhere linksventrikuläre Muskelmasse (152,38±43,57 vs. 134,41±27,19g/m2, p<0,01) und häufiger eine leichtgradige Mitralinsuffizienz (38,1 vs. 28,6%, p<0,01) als Patienten mit durchgehendem Sinusrhythmus. Die multivariate Regressionsanalyse erbrachte als unabhängige Parameter für das Auftreten von Vorhofflimmern die Größe des linken Vorhofes und das Vorhandensein einer Mitralinsuffizienz. Für die Vergrößerung des linken Vorhofes wurden ebenfalls die Mitralinsuffizienz, aber auch die linksventrikuläre Muskelmasse als unabhängige Parameter identifiziert. Zusammenfassung: Diese Studie zeigt, dass paroxysmales Vorhofflimmern bei Hypertonikern vor allem durch die linksatriale Größe bestimmt wird, welche aber wiederum insbesondere durch die linksventrikuläre Muskelmasse beeinflusst wird. Damit sollten diese Ergebnisse vorherrschend zu einer Kausaltherapie zur Behandlung von paroxysmalem Vorhofflimmern bei diesen Patienten führen.