Bernward Lauer

Antimyosin autoantibodies are associated with deterioration of systolic and diastolic left ventricular function in patients with chronic myocarditis.

OBJECTIVESnThe study evaluates the clinical course and the development of systolic and diastolic left ventricular function in patients with chronic myocarditis with or without autoantibodies against cardiac myosin.nnnBACKGROUNDnPatients with myocarditis often show autoantibodies against cardiac myosin. The clinical and pathophysiologic significance of these antimyosin autoantibodies (AMAAB) is yet unknown. The results from studies comparing the clinical course and the development of left ventricular function in patients with chronic myocarditis with or without AMAAB are not yet available.nnnMETHODSnThirty-three patients with biopsy proven chronic myocarditis underwent analysis of AMAAB, right and left heart catheterization and left ventriculography at baseline and after six months. Left ventricular volumes and ejection fraction as well as the time constant of left ventricular relaxation tau and the constant of myocardial stiffness b were determined at baseline and at follow-up.nnnRESULTSnIn 17 (52%) patients, AMAAB could be detected at baseline. After six months, AMAAB were still found in 13 (76%) initially antibody-positive patients. No initially antibody-negative (n = 16) patient developed AMAAB during follow-up. Clinical symptoms improved slightly in antibody-negative patients and remained stable in antibody-positive patients. Left ventricular ejection fraction developed significantly better in antibody-negative patients (+8.9 +/- 10.1%) compared with antibody-positive patients (-0.1 +/- 9.4%) (p < 0.012). Stroke volume (SV) and stroke volume index (SVI) also improved in antibody-negative patients (SV: +20 +/- 31 ml; SVI: +10 +/- 17 ml) compared with antibody-positive patients (SV: -14 +/- 43 ml; SVI: -8 +/- 22 ml) (SV: p < 0.015; SVI: p < 0.016). Left ventricular end-diastolic and end-systolic volumes and the time constant of left ventricular relaxation tau did not change significantly different in antibody-positive and antibody-negative patients. The constant of myocardial stiffness b improved significantly in antibody-negative patients (-6.1 +/- 10.8) compared with antibody-positive patients (+7.3 +/- 22.6) (p < 0.040). Analyzing only the persistently antibody-positive patients yielded essentially the same results.nnnCONCLUSIONSnAntimyosin autoantibodies are associated with worse development of left ventricular systolic function and diastolic stiffness in patients with chronic myocarditis.

Catheter-based percutaneous myocardial laser revascularization in patients with end-stage coronary artery disease

OBJECTIVESnThis study evaluates the feasibility and safety of a catheter-based laser system for percutaneous myocardial revascularization and analyses the first clinical acute and long-term results in patients with end-stage coronary artery disease (CAD) and severe angina pectoris.nnnBACKGROUNDnIn patients with CAD and intractable angina who are not candidates for either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), transmyocardial laser revascularization (TMR) has been developed as a new treatment that results in reduced angina pectoris and increased exercise capacity. However, surgical thoracotomy is required for TMR with considerable morbidity and mortality.nnnMETHODSnA catheter-based system has been developed that allows creation of laser channels in the myocardium from within the left ventricular cavity. Laser energy generated by a Holmium: YAG (Cardiogenesis Corporation, Sunnyvale, California) laser was transmitted to the myocardium via a flexible optical fiber capped by an optic lens. The optical fiber was maneuvered to the target area under biplane fluoroscopy through a coaxial catheter system permitting movement in three dimensions.nnnRESULTSnThirty-four patients with severe CAD not amenable to either CABG or PTCA and refractory angina pectoris (Canadian Cardiologic Society [CCS] Angina Scale Class III-IV) were included in the study. Ischemic regions were identified by coronary angiography and confirmed by thallium scintigraphy. The percutaneous myocardial revascularization (PMR) procedure was successfully completed in all patients. In 29 patients, one vascular territory of the left ventricle and in 5 patients, two vascular territories were treated. Eight to fifteen channels were created in each ischemic region. Major periprocedural complications were limited to an episode of arterial bleeding requiring surgical repair. There was one death early after PMR, due to a myocardial infarction (MI) in a nontreated region. Clinical follow-up at 6 months (17 patients) demonstrated significant improvement of angina pectoris (CCS class before PMR: 3.0+/-0.0, six months after PMR: 1.3+/-0.8, p<0.0001) and increased exercise capacity (exercise time on standard bicycle ergometry before PMR: 384+/-141 s, six months after PMR: 514+/-158 s, p<0.05), but thallium scintigraphy failed to show improved perfusion of the laser treated regions.nnnCONCLUSIONSnPercutaneous myocardial revascularization is a new safe and feasible therapeutic option in patients with CAD and severe angina pectoris not amenable to either CABG or PTCA. Initial results show immediate and significant improvement of symptoms and exercise capacity but evidence of improved myocardial perfusion is still lacking.

Initial results of laser-based percutaneous myocardial revascularization for angina pectoris

Results of a 30-patient pilot study of a recently developed percutaneous myocardial revascularization approach are described. The feasibility and positive safety profile of percutaneous myocardial revascularization are clearly demonstrated, with no mortality associated with the treatment or in the immediate post-treatment period and an incidence of only 1 major complication.

Antimyosin scintigraphy and immunohistologic analysis of endomyocardial biopsy in patients with clinically suspected myocarditis—evidence of myocardial cell damage and inflammation in the absence of histologic signs of myocarditis

OBJECTIVESnThis study compares the results of antimyosin scintigraphy in patients with clinically suspected myocarditis with histologic and immunohistologic findings in the endomyocardial biopsy.nnnBACKGROUNDnIn patients with clinically suspected myocarditis, antimyosin scintigraphy often demonstrates myocardial cell damage but histologic evaluation of the endomyocardial biopsy often fails to show evidence of myocarditis. Recently developed immunohistologic techniques appear to be more sensitive for the detection of myocardial inflammation than histologic analysis alone. Studies comparing antimyosin scintigraphy and immunohistologic analysis of the endomyocardial biopsy in patients with clinically suspected myocarditis are not yet available.nnnMETHODSnSixty-five patients with clinically suspected myocarditis underwent antimyosin scintigraphy. Antimyosin antibody uptake was correlated with histologic and immunohistologic findings in the endomyocardial biopsy.nnnRESULTSnAntimyosin scintigraphy showed evidence of myocardial cell damage in 36 (55%) of the 65 patients and was negative in 29 (45%) patients. Histologic analysis of the endomyocardial biopsy revealed myocarditis in nine patients: six had a positive and three had a negative antimyosin scan, respectively. Thirty (83%) of 36 patients with evidence of myocardial cell damage on antimyosin scintigraphy were histologically negative for myocarditis. Immunohistologic analysis showed evidence of myocarditis in 31 (86%) of 36 patients with a positive antimyosin scan and also in 17 (59%) of 29 patients with a normal scan (p < 0.047).nnnCONCLUSIONSnAntimyosin scintigraphy often shows myocyte injury in patients with clinically suspected myocarditis. Histologic analysis of the endomyocardial biopsy alone is often negative, but additional immunohistologic analysis of the endomyocardial biopsy frequently provides evidence of myocardial inflammation in these patients. With immunohistologic analysis as the reference method, antimyosin scintigraphy has a high specificity but a lower sensitivity for the detection of myocarditis.

Short- and long-term hemodynamic effects of intra-aortic balloon support in ventricular septal defect complicating acute myocardial infarction

In patients with an infarct-related ventricular septal defect, an intra-aortic balloon pump provides immediate and long-term hemodynamic improvement, resulting in an enhanced effective cardiac output and a reduced left-to-right-shunt and shunt flow ration. In patients who can be stabilized or remain stable, there is no habituation to the effects of the intra-aortic balloon pump; thus, later surgical closure of the ventricular septal defect might be possible in some patients.

Influence of Residual Stenosis After Percutaneous Coronary Intervention With Stent Implantation on Development of Restenosis and Stent Thrombosis

The aim of this study was to assess the effects of residual stenosis after single-stent implantation on the rate of stent thrombosis, as well as restenosis within a 6-month follow-up period. Coronary angiograms of 2,157 patients with 2,523 lesions treated with a single stent were analyzed by quantitative coronary angiography before, immediately after stent implantation, and at a planned 6-month follow-up. Lesions were classified into 4 subgroups according to the degree of residual stenosis after stent implantation: group 1, gross oversizing <-15%; group 2, slight oversizing -15% to <0%; group 3, mild residual 0% to <15%; group 4, moderate residual 15% to <30%. Stent thrombosis rates were not significantly different among the 4 subgroups (group 1: 0 of 60 [0%]; group 2: 2 of 388 [0.5%]; group 3: 8 of 1,370 [0.6%]; group 4: 8 of 705 [1.1%]; p = NS for all). An adequate dosage of ticlopidine (250 mg twice daily) and aspirin (100 mg/day) led to a lower rate of stent thrombosis (6 of 2,189 cases) than inadequate dosages or missing therapy (12 of 343 cases). In 1,882 stenoses with angiographic follow-up (77.7%), gross oversizing of stents lead to a significantly higher increase of percent stenosis (p <0.001) associated with a higher restenosis rate (group 1: 34.7% vs groups 2, 3, and 4: 32.5%, 28.2%, and 29.6%, respectively). A multiple regression analysis was performed. Optimal results with regard to stent thrombosis and restenosis were achieved with mild residual stenoses between 0% and 15% after stent implantation. Oversizing of stents is no longer necessary with an adequate dosage of ticlopidine and aspirin.

Contemporary outcome of cardiac catheterizations in 1085 consecutive octogenarians

BACKGROUNDnA growing number of patients > or = 80 years require cardiac catheterization. Since little is known about the overall safety of these procedures in this population, we assessed the procedure-related risks and determined predictors for complications.nnnMETHODSnWe studied 1085 consecutive patients > or = 80 years (82.6+/-2.6 years; 526 males, 544 females), who underwent 1384 cardiac catheterizations in a tertiary specialist university hospital (3% of 43,517 procedures).nnnRESULTSnA total of 373 patients (35%) required percutaneous coronary interventions (PCI), and 331 (31%) received coronary artery bypass surgery. Thirty-one patients died during hospital stay. Procedure-related complications including vascular injuries occurred in 2.1% after CATH and 11.6% after PCI.nnnCONCLUSIONSnDespite the widespread notion that cardiac catheterization exposes patients > or = 80 years to an unwarranted risk, these data demonstrate an acceptable complication rate. Patients #10878;80 years of age should thus not be refused to undergo cardiac catheterization merely based on their age.

Prospective randomized comparison of early and late results of 4 different stent designs

BACKGROUNDnLate results of interventional procedures using coronary stents are largely determined by the rate of restenosis. So far, few data are available addressing the effect of stent design on this crucial variable and on early and late adverse events after stent implantation.nnnMETHODSnFrom 1996 through 1998, a total of 965 lesions in 925 patients with coronary artery disease were randomized to treatment with 1 of 4 different stent designs (Micro stent II [M] AVE, Düsseldorf, Germany; Sito [S] Sitomed, Rangendingen, Germany; Pura Vario [PV], Devon, Hamburg, Germany; Inflow [ID] Inflow Dynamics, München, Germany). The primary end point of the study was the degree of diameter stenosis measured by quantitative coronary angiography 6 months after stent implantation.nnnRESULTSnDiameter stenosis at 6 months follow-up was not different in the 4 study arms (M 40.3 +/- 24.1, S 42.8 +/- 27.0, PV 42.6 +/- 26.9 and ID 42.3 +/- 26.8, P =.7). No significant differences could be detected in net lumen gain and late lumen loss, resulting in comparable restenosis rates (>or=50% diameter stenosis) at follow-up (M 26.0%, S 30.5%, PV 31.3%, and ID 28.7%, P =.7). Early adverse events like stent loss, stent thrombosis, periinterventional acute myocardial infarctions and emergency coronary artery bypass graft also showed no significant differences. Multivariate regression analyses revealed reference vessel diameter <3.0 mm, overall stented length, a history of bypass grafting, localization of the target lesion in the left anterior descending coronary artery, type C lesions, dissection before stent implantation, and diabetes mellitus to be independent predictors for restenosis.nnnCONCLUSIONnStent design does not have significant influence on development of restenosis. Adverse event rates were similar with all stent types used in this trial.

Antimyosin-Szintigraphie zur Diagnostik und Verlaufskontrolle bei Patienten mit klinischem Verdacht auf Myokarditis

Für die Diagnostik der Myokarditis wird bisher der Antimyosin-Szintigraphie eine hohe Spezifität, jedoch eine geringe Sensitivität zugewiesen. Hierfür wurde bisher die Antimyosin-Szintigraphie mit der allein histologischen Aufarbeitung der Endomyokardbiopsie verglichen. Die histologische Analyse der Myokardbiopsie scheint jedoch selbst nur eine geringe Sensitivität für die Diagnose einer Myokarditis zu haben. Daher wurden in den letzten Jahren zusätzlich immunhistologische Methoden zum Nachweis lymphozytärer Infiltrate im Myokard etabliert. In der vorliegenden Studie werden die Ergebnisse der Antimyosin-Szintigraphie mit den Befunden der histologischen sowie zusätzlich der immunhistologischen Analyse der Myokardbiopsie verglichen. Bei 65 Patienten mit klinischem Verdacht auf eine Myokarditis wurden eine Antimyosin-Szintigraphie durchgeführt sowie die Myokardbiopsie mit histologischen und immunhistologischen Methoden analysiert. Bei 36 Patienten mit positivem Antimyosin-Szintigramm konnte durch die allein histologische Beurteilung der Myokardbiopsie nur bei 9 (25%) Patienten eine Myokarditis diagnostiziert werden, die immunhistologische Aufarbeitung wies jedoch lymphozytäre Infiltrate bei 31 (86%) dieser Patienten nach. Bei 29 Patienten mit unauffälligem Antimyosin-Szintigramm diagnostizierte die allein histologische Beurteilung der Myokardbiopsie eine Myokarditis bei 3 (10%) Patienten, die immunhistologische Analyse zeigte lymphozytäre Infiltrate bei 17 (59%) dieser Patienten. Bei immunhistologischer Aufarbeitung der Myokardbiopsie als Referenzmethode muß somit der Antimyosin-Szintigraphie eine hohe Sensitivität, jedoch eine geringere Spezifität für die Diagnostik der Myokarditis zugerechnet werden. Bei Patienten mit einer Myokarditis, bei denen im Serum Autoantikörper gegen kardiales Myosin nachgewiesen werden konnten, lag die Inzidenz positiver Antimyosin-Szintigramme deutlich niedriger als bei Patienten mit Myokarditis ohne Antimyosin-Autoantikörper. Bei 14 Patienten mit Myokarditis wurde nach 6 Monaten erneut eine Antimyosin-Szintigraphie durchgeführt. Jetzt konnte histologisch oder immunhistologisch eine Myokarditis bei 3/8 Patienten mit positivem Antimyosin-Szintigramm sowie bei 5/6 Patienten mit unauffälligem Antimyosin-Szintigramm nachgewiesen werden. Somit erscheint die Antimyosin-Szintigraphie zur Verlaufskontrolle einer Myokarditis weniger hilfreich. Antimyosin-scintigraphy is believed to have a high specificity but a low sensitivity for the diagnosis of myocarditis when histological analysis of endomyocardial biopsy is used as the reference method. However, the histological evaluation itself seems to have a low sensitivity for the diagnosis of myocarditis. Therefore, immunohistological techniques have been developed for the detection of lymphocytic infiltrates and increased expression of HLA antigens in the myocardium. The present study compares the results of antimyosin-scintigraphy with histological and immunohistological analysis of the endomyocardial biopsy. 65 patients with clinically suspected myocarditis underwent antimyosin-scintigraphy and histological and immunohistological analysis of the endomyocardial biopsy. Myocarditis could be diagnosed histologically in only 9/36 (25%) patients with a positive antimyosin scan but additional immunohistological analysis revealed lymphocytic infiltrates in 31 (86%) of these patients. In 29 patients with a normal antimyosin scan, histological analysis showed evidence of myocarditis in 3 (10%) patients; additional immunohistological evaluation disclosed lymphocytic infiltrates in 17 (59%) patients. With immunohistological analysis of the endomyocardial biopsy as the reference method, antimyosin-scintigraphy has a high sensitivity but a lower specificity for the diagnosis of myocarditis. Detection of autoantibodies against human cardiac myosin in patients with myocarditis is associated with a significantly lower incidence of positive antimyosin scans in these patients. Antimyosin-scintigraphy was repeated after six months in 14 patients with myocarditis. Histological and immunohistological evaluation of the endomyocardial biopsy now showed persistent myocarditis in 3/8 patients with a positive antimyosin scan and in 5/6 patients with a normal antimyosin scan.

Myokardiale Laserrevaskularisation bei therapierefraktärer Angina pectoris

In patients with coronary artery disease and intractable angina, who are not candidates for either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), transmyocardial laser revascularization (TMR) has been developed as a new treatment. Several recently published, randomized trials have consistently shown improvement of clinical symptoms and increased exercise capacity after TMR compared to medical therapy.¶u2002u2009u2009However, surgical thoracotomy is required for TMR with considerable morbidity and mortality. Therefore, catheter-based systems have been developed, which allow creation of laser channels in the myocardium from within the left ventricular cavity. These systems for „percutaneous myocardial revascularization” (PMR) use laser energy generated by Holmium:YAG lasers, which can be transmitted to the myocardium via flexible optical fibers.¶u2002u2009u2009PMR leads to significant improvement of clinical symptoms and increased exercise capacity similar to TMR. The CCS classification is improved about 1.5 classes, independent of the PMR system used. However, evidence of improved perfusion after PMR is still lacking.¶u2002u2009u2009The pathophysiologic mechanisms of myocardial laser revascularization are still poorly understood. Experimental studies indicate myocardial neoangiogenesis and myocardial denervation after TMR; however, clinical studies have not yet found evidence of improved myocardial perfusion after myocardial laser revascularization. Für Patienten mit schwerer Angina pectoris aufgrund einer koronaren Herzerkrankung, bei denen aufgrund der Koronarmorphologie oder vorausgegangener Interventionen keine Möglichkeit einer Ballondilatation oder einer Bypass-Operation mehr besteht, steht mit der transmyokardialen Laserrevaskularisation (TMR) ein neues Therapieverfahren zur Verfügung. In mehreren randomisierten Studien konnte gezeigt werden, daß bei diesen Patienten durch eine TMR die klinische Symptomatik gebessert und die körperliche Belastbarkeit gesteigert werden kann.¶u2009u2009u2002Ein Nachteil der TMR ist die Notwendigkeit eines chirurgischen Zugangs zum Herzen, um die Kanäle vom Epikard aus in das Myokard einzubringen. Daher wurden Katheter-Systeme entwickelt, mit denen die Laserkanäle vom linksventrikulären Kavum aus in das Myokard eingebracht werden können. Diese Systeme für die „perkutane myokardiale Laserrevaskularisation“ (PMR) verwenden einen Holmium-YAG-Laser, bei dem die Laserenergie über optische Fasern zum Herzen übertragen werden kann.¶u2009u2009u2002Eine PMR führt zu einer ähnlichen Besserung der klinischen Symptomatik und zu einer Steigerung der körperlichen Belastbarkeit wie die TMR. Der Schweregrad der Angina pectoris wird um ca. 1,5 CCS-Klassen gebessert, unabhängig vom verwendeten Kathetersystem. Eine Verbesserung der myokardialen Perfusion nach PMR konnte allerdings bisher noch nicht nachgewiesen werden.¶u2009u2009u2002Die pathophysiologischen Mechanismen der myokardialen Laserrevaskularisation sind zum jetzigen Zeitpunkt noch nicht geklärt. Experimentelle Studien deuten auf eine myokardiale Angioneogenese und auf eine myokardiale Denervierung nach TMR hin, in klinischen Studien konnte jedoch eine gesteigerte myokardiale Durchblutung bisher noch nicht nachgewiesen werden.