Claudius Teupe

Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI)

Background—Experimental studies suggest that transplantation of blood-derived or bone marrow–derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown. Methods and Results—We randomly allocated 20 patients with reperfused acute myocardial infarction (AMI) to receive intracoronary infusion of either bone marrow–derived (n=9) or circulating blood–derived progenitor cells (n=11) into the infarct artery 4.3±1.5 days after AMI. Transplantation of progenitor cells was associated with a significant increase in global left ventricular ejection fraction from 51.6±9.6% to 60.1±8.6% (P =0.003), improved regional wall motion in the infarct zone (−1.5±0.2 to −0.5±0.7 SD/chord;P <0.001), and profoundly reduced end-systolic left ventricular volumes (56.1±20 mL to 42.2±15.1 mL;P =0.01) at 4-month follow-up. In contrast, in a nonrandomized matched reference group, left ventricular ejection fraction only slightly increased from 51±10% to 53.5±7.9%, and end-systolic volumes remained unchanged. Echocardiography revealed a profound enhancement of regional contractile function (wall motion score index 1.4±0.2 at baseline versus 1.19±0.2 at follow-up;P <0.001). At 4 months, coronary blood flow reserve was significantly (P <0.001) increased in the infarct artery. Quantitative F-18-fluorodeoxyglucose–positron emission tomography analysis revealed a significant (P <0.01) increase in myocardial viability in the infarct zone. There were no differences for any measured parameter between blood-derived or bone marrow–derived progenitor cells. No signs of an inflammatory response or malignant arrhythmias were observed. Conclusions—In patients with AMI, intracoronary infusion of autologous progenitor cells appears to be feasible and safe and may beneficially affect postinfarction remodeling processes.

Late (Five to Nine Years) Follow-Up After Balloon Dilation of Valvular Pulmonary Stenosis in Adults

The transvalvular gradient was investigated in 14 patients with pulmonary stenosis 5 to 9 years after balloon valvuloplasty. None of the patients had developed restenosis, and in those who had a peak gradient >100 mm Hg before valvuloplasty, the gradient decreased further due to resolution of subvalvular muscular hypertrophy within 3 months after intervention.

Thromboembolic Risk of Patients Referred for Radiofrequency Catheter Ablation of Typical Atrial Flutter Without Prior Appropriate Anticoagulation Therapy

GRÖNEFELD, G.C., et al.: Thromboembolic Risk of Patients Referred for Radiofrequency Catheter Ablation of Typical Atrial Flutter Without Appropriate Prior Anticoagulation Therapy. Background: Radiofrequency catheter ablation of isthmus dependent atrial flutter is considered the therapy of choice. There is, however, controversy with regard to the thrombogenicity of atrial flutter in comparison with atrial fibrillation. Methods: Consecutive patients scheduled for catheter ablation of documented typical atrial flutter receiving insufficient (INR < 2.0) or no anticoagulation during the three weeks preceding the procedure underwent multiplane transesophageal echocardiography (TEE). Patients with exclusive documentation of atrial flutter were classified as group I, whereas patients with additional documentation of atrial fibrillation were classified as group II. Results: The study included 201 patients, 62 of whom were not on therapeutic anticoagulation (mean age 64 ± 9 years, 87% men). In 10 of these 62 patients (16%), TEE detected a left atrial (LA) appendage thrombus in 4, or dense spontaneous echo contrast (SEC) in 6 patients. Comparison of patients with versus without SEC or thrombus, revealed a higher incidence of valvular heart disease (60% vs 26%, P = 0.05 ), but no differences with respect to age, gender, LA diameter, left ventricular end‐diastolic diameter, or left ventricular ejection fraction. The incidence of positive TEE findings in group I was 1 in of 36 versus 9 of 26 in group II (3% vs 35%, P < 0.001), and the relative risk for thromboembolism in group II versus group I was 12.5 (95% CI: 3‐55, P < 0.001). Conclusion: There is a significant risk for thromboembolism in patients referred for ablation of typical atrial flutter who have not been appropriately anticoagulated. (PACE 2003; 26[Pt. II]:323–327)

Platypnea-orthodeoxia due to osteoporosis and severe kyphosis: a rare cause for dyspnea and hypoxemia

Platypnea orthodeoxia is a rare disorder characterized by dyspnea and arterial desaturation, exacerbated by the upright position and relieved when the subject is recumbent. We report the case of a 79-year old woman admitted to hospital with dyspnea who was thought to have restrictive ventilatory impairment due to osteoporosis and severe kyphosis. Interestingly, the dyspnea was aggravated in the upright position, whereas the symptoms improved in the supine position. Arterial blood gas analysis confirmed orthodeoxia. The lung function test showed only a mild obstructive and restrictive ventilation disorder. Echocardiography revealed a patent foramen ovale and an aneurysm of the atrial septum protruding into the left atrium, despite normal right atrial pressure. Transesophageal echocardiography showed a prominent Eustachian valve guiding a blood flow from the inferior vena cava directly onto the atrial septum, thereby pushing open the patent foramen ovale. Contrast-enhanced echocardiography confirmed a spontaneous right-to-left shunt through the patent foramen ovale. It was assumed that the platypnea-orthodeoxia was caused by a prominent Eustachian valve redirected to the patent foramen ovale as a result of severe osteoporosis with subsequent thoracic kyphosis and a change in the position of the entire heart. The patient underwent permanent transcatheter closure of the patent foramen ovale after hemodynamic assessment had confirmed a significant right-to-left shunt through it. After the procedure the arterial oxygen pressure increased significantly in the upright position and dyspnea improved.

Ballondilatation valvulärer Pulmonalstenosen bei Erwachsenen

Die Behandlung von valvulären Pulmonalstenosen mittels Ballondilatation ist heute die Therapie der Wahl im Kindes- und Erwachsenenalter. Wir berichten über das Dilatationsergebnis von 46 erwachsenen Patienten (mittleres Alter 37 ± 17 Jahre) mit Pulmonalstenose, die zwischen 1984 und 1994 mit diesem Verfahren behandelt worden sind. 34 von 46 Patienten wurden 3 Monate bis 9 Jahre (im Mittel 3,4 Jahre) nach Intervention mittels Rechtsherzkatheterisierung und Echokardiographie nachuntersucht. Diese 34 Patienten waren bezüglich Alter, Schwere der Pulmonalstenose und Akutergebnis nach Dilatation repräsentativ für das Gesamtkollektiv. Der maximale Druckgradient wurde durch Ballonvalvuloplastie akut von 86 ± 35 auf 38 ± 17 mm Hg (p < 0,0001) (n = 46) reduziert und war 32 ± 10 mm Hg (n.s.) (n = 34) zum Zeitpunkt der jeweils letzten Nachuntersuchung. 8 von 13 Patienten mit einem maximalen Druckgradienten ≥ 100 mm Hg zeigten eine weitere spontane Reduktion des Gradienten infolge Rückbildung einer subvalvulären muskulären Hypertrophie des rechten Ausflußtraktes innerhalb von 3 Monaten nach dem Eingriff. Eine fahrradergometrische Untersuchung im Liegen wurde bei 9 Patienten durchgeführt. Hierbei stieg der invasiv gemessene maximale Gradient signifikant von 29 ± 10 auf 52 ± 23 mm Hg (p < 0,01) an. Sämtliche Patienten hatten ein normales Herzzeitvolumen in Ruhe und unter Belastung. Keiner zeigte elektro- oder echokardiographisch die Zeichen einer rechtsventrikulären Hypertrophie. Die Ballonvalvuloplastie der valvulären Pulmonalstenose ist die Therapie der Wahl bei Erwachsenen. Balloon valvuloplasty of pulmonary stenosis has become the treatment of choice in children and adults. This is a report about the long term results in adult patients. Forty-six patients (mean age 37 ± 17 years) with pulmonary stenosis were treated between 1984 and 1994 by this method. Thirty-four of 46 patients were re-examined 3 months to 9 years (mean 3.4 years) later by right heart catheterization and echocardiography. These 34 patients were representative for the whole group concerning age, severity of the pulmonary stenosis, and acute results after the intervention. The pressure gradient was acutely reduced by balloon valvuloplasty from 86 ± 35 to 38 ± 17 mm Hg (p < 0.0001) (n = 46) and was 32 ± 10 mm Hg (n.s.) (n = 34) at follow-up. Within 3 months after the intervention, 8 of 13 patients with a pressure gradient ≥ 100 mm Hg, showed spontaneously further reduction of the gradient due to the resolution of the subvalvular muscular hypertrophy. During a bicycle exercise test with 9 patients, the gradient rose significantly from 29 ± 10 to 53 ± 23 mm Hg (p < 0.01) as determined by right heart catheterization. All of these patients had normal cardiac output at rest and during exercise. None had signs of right ventricular hypertrophy in the electro- or echocardiogram. It is concluded that balloon valvuloplasty of pulmonary stenosis is the first line treatment in adults.

Myokardiale Kontrastechokardiografie mit harmonischem Power Doppler Verfahren und dem lungengängigen Ultraschallkontrastmittel SHU 563A zur Darstellung von myokardialen Perfusionsstörungen Tierexperimentelle Untersuchungen bei akuter Ischämie und nach Reperfusion

The current approach for the assessment of myocardial perfusion using contrast echocardiography involves black-and-white gray scale imaging in b-mode. For better appreciation of perfusion abnormalities, off-line postprocessing techniques including color encoding are used. In this study, we examined whether we could exploit the contrast microbubble response to high ultrasound amplitude – the phenomenon of stimulated acoustic emission – that could be recorded with harmonic power Doppler (HPD) in color to identify myocardial perfusion defects. To assess the potential of HPD, we occluded branches of the left coronary artery for 2–3h followed by 1h reperfusion in 10 dogs. After transvenous administration of the new air-filled contrast agent SHU 563A, echocardiographic imaging was performed with ECG-triggered harmonic b-mode (HBM) and the harmonic power Doppler (HPD) approach in different short (SAX) and long axis (LAX) views. Post-mortem TTC staining was performed to verify infarction. HBM, HPD and TTC data were analyzed by independent observers. During coronary occlusion, HPD with SHU 563A showed perfusion defects in 10 dogs in all SAX and LAX views. HBM demonstrated perfusion defects in all dogs in SAX and in 8 dogs in LAX. The correlation of perfusion defect size between HPD and HBM images was good (SAX: r=0.9, p<0.001, LAX: r=0.7, p<0.01). One hour after reperfusion, both HPD and HBM showed perfusion defects with SHU 563A in 7 dogs. Five dogs showed TTC evidence of infarction. Perfusion defect size by HPD correlated well with residual infarct size (r=0.8, p<0.01), while defect size by HBM showed poor correlation (r=0.3, p=ns).    Myocardial contrast echocardiography with HPD and contrast agent SHU 563A identifies perfusion defects in acute coronary occlusion as reliably as HBM. After reperfusion HPD and SHU 563A accurately portray the site and size of residual myocardial infarction on line, in color. This approach has excellent potential for clinical application. Die bisher in der myokardialen Kontrastechokardiografie verwendete b-mode Technik stellt unterschiedliche Perfusionszustände in Schwarz-Weißbildern mit verschiedenen Graustufen dar. Durch nachträgliche Bildbearbeitung und Farbkodierung kann die Erkennung von Perfusionsstörungen verbessert werden. In einer tierexperimentellen Studie untersuchten wir, ob Perfusionsdefekte mit harmonischem Power Doppler Verfahren und dem neuartigen, lungengängigen Ultraschallkontrastmittel SHU 563A direkt in Farbe abgebildet werden können. Bei 10 Hunden wurden Äste der linken Koronararterie für 2–3 Stunden okkludiert und anschließend reperfundiert. Nach Okklusion und Reperfusion erfolgte die EKG-getriggerte Bildakquisation mit harmonischem b-mode (HBM) bzw. Power Doppler (HPD) nach intravenöser Injektion des Ultraschallkontrastmittels in verschiedenen Kurz- (SAX) und Längsachsenschnitten (LAX). Myokardnekrosen wurden postmortal durch TTC-Färbung verifiziert. Verschiedene Untersucher analysierten die echokardiografischen und anatomischen Befunde. Nach akuter Koronarokklusion zeigte HPD Perfusionsdefekte bei 10 Hunden in allen SAX- und LAX-Schnitten, während mit HBM Perfusionsdefekte bei 10 bzw. 8 Hunden nachgewiesen wurden. Es bestand eine gute Korrelation zwischen HPD und HBM bezüglich der Defektgröße während Okklusion (SAX: r=0,9, p<0,001, LAX: r=0,7, p<0,01). Nach Reperfusion zeigten HPD und HBM Perfusionsdefekte bei 7 Hunden. Bei 5 Hunden konnten Myokardinfarkte mittels TTC-Färbung nachgewiesen werden. Das Ausmaß der durch HPD dargestellten Perfusionsdefekte korrelierte eng mit der anatomischen Infarktgröße (r=0,8, p<0,01), während HBM eine schlechte Korrelation zeigte (r=0,3, p=ns).    Die myokardiale Kontrastechokardiografie mit HPD und dem Kontrastmittel SHU 563A kann Perfusionsdefekte bei akutem Koronarverschluss ebenso zuverlässig wie HBM nachweisen. Nach Reperfusion werden mit HPD Ort und Größe des residualen Myokardinfarkts genau dargestellt. Dieses Verfahren erscheint vielversprechend für eine klinische Anwendung.