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Percutaneous coronary excimer laser angioplasty in patients with stable and unstable angina pectoris. Acute results and incidence of restenosis during 6-month follow-up.

A clinical study was conducted to evaluate the efficacy and safety of percutaneous coronary excimer laser angioplasty in 60 patients with coronary artery disease. Forty-nine patients had stable exertional angina, and 11 patients had unstable angina despite medical therapy. A novel 1.4-mm diameter catheter with 20 quartz fibers of 100-microns diameter each arranged concentrically around a central lumen suitable for a 0.014-in. flexible guide wire was coupled to an excimer laser. A commercial excimer laser emitting energy at a wavelength of 308 nm with a pulse duration of 60 nsec was used. The laser was operated at 20 Hz. Mean energy transmission was 30 +/- 5 mJ/mm2. In five of the 60 patients, laser angioplasty was not attempted. In 23 patients with laser ablation alone, percent stenosis decreased from 76 +/- 14% before to 27 +/- 17% after ablation and was 34 +/- 15% at the early follow-up angiogram. In 32 patients, additional balloon angioplasty was performed because of vessel closure after laser ablation in 11 and an insufficient qualitative result in 21 patients. Of the 11 patients with unstable angina, one patient died due to vessel closure 3 hours after intervention, and two patients developed a myocardial infarction. In 22 of 47 patients with late follow-up angiography, restenosis within the 6-month follow-up period occurred. Rate of restenosis was higher in patients treated with laser ablation and balloon angioplasty (16 of 28) than in patients treated with laser ablation alone (six of 19). These results suggest that coronary excimer laser angioplasty for ablation of obstructive lesions is feasible and safe in patients with stable angina. However, development of new catheter systems is necessary for an improved success rate.

Alterations of Coagulation and Fibrinolytic and Kallikrein-Kinin Systems in the Acute and Postacute Phases in Patients With Unstable Angina Pectoris

BACKGROUND Unstable angina pectoris is frequently associated with intracoronary thrombus formation. In a prospective study, we investigated in 35 patients with unstable angina pectoris markers of coagulation and the kallikrein-kinin and fibrinolytic systems in the acute and postacute phases. METHODS AND RESULTS We determined serially in the patients up to 10 days after admission factor XII and the beta-factor XIIa inhibition, kallikrein-like activity, prekallikrein, C1-esterase inhibitor, kallikrein inhibition, high molecular weight kininogen as indicators of the contact phase and bradykinin generation, thrombin-antithrombin III (TAT) complex as marker of the activated coagulation cascade, fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (TPA), and D-dimers as indicators of the fibrinolytic system. Data were compared with those from control subjects (n = 25) and from patients with stable angina pectoris (n = 25). In patients with unstable angina pectoris, initially the contact phase and the kallikrein-kinin system were markedly elevated (factor XII, 96 +/- 5% versus 117 +/- 5%; kallikrein-like activity, 35.7 +/- 2.9 versus 27.4 +/- 1.3 U/L; high molecular weight kininogen, 52.7 +/- 5.2% versus 87.7 +/- 3.9%; P < .01 versus control subjects). Contact-phase activation persisted for the following 10 days, whereas the initially enhanced bradykinin generation normalized after 2 days. Furthermore, we had evidence of a hypercoagulative state (TAT, 10.9 +/- 3.1 versus 4.5 +/- 0.7 micrograms/L, P < .05; D-dimer, 474 +/- 81 versus 272 +/- 71 ng/mL) persisting longer than the clinically symptomatic period in association with disturbed fibrinolysis (TPA, 15.9 +/- 1.9 versus 5.1 +/- 0.4 ng/mL; P < .01; PAI-1, 9.9 +/- 2.6 versus 4.6 +/- 1.6 AU/mL; P = NS) in the presence of elevated fibrinogen levels. CONCLUSIONS Our data indicate that in patients with unstable angina pectoris, intracoronary thrombus formation is associated with a hypercoagulative state, including activation of the contact phase and of the kallikrein system and increased bradykinin generation. The persistence of this hypercoagulative state, together with a disturbed fibrinolysis, might indicate an increased risk for further coronary events.

Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces ICa,Land Itoin rapid atrial pacing in rabbits ☆

OBJECTIVES The purpose of the study was to characterize the ionic and molecular mechanisms in the very early phases of electrical remodeling in a rabbit model of rapid atrial pacing (RAP). BACKGROUND Long-term atrial fibrillation reduces L-type Ca(2+) (I(Ca,L)) and transient outward K(+) (I(to)) currents by transcriptional downregulation of the underlying ionic channels. However, electrical remodeling starts early after the onset of rapid atrial rates. The time course of ion current and channel modulation in these early phases of remodeling is currently unknown. METHODS Rapid (600 beats/min) right atrial pacing was performed in rabbits. Animals were divided into five groups with pacing durations between 0 and 96 h. Ionic currents were measured by patch clamp techniques; messenger ribonucleic acid (mRNA) and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULTS L-type calcium current started to be reduced (by 47%) after 12 h of RAP and continued to decline as pacing continued. Current changes were preceded or paralleled by decreased mRNA expression of the Ca(2+) channel beta subunits CaB2a, CaB2b, and CaB3, whereas significant reductions in the alpha(1) subunit mRNA and protein expression began 24 h after pacing onset. Transient outward potassium current densities were not altered within the first 12 h, but after 24 h, currents were reduced by 48%. Longer pacing periods did not further decrease I(to). Current changes were paralleled by reduced Kv4.3 mRNA expression. Kv4.2, Kv1.4, and the auxiliary subunit KChIP2 were not affected. CONCLUSIONS L-type calcium current and I(to) are reduced in early phases of electrical remodeling. A major mechanism appears to be transcriptional downregulation of underlying ion channels, which partially preceded ion current changes.

Influence of sampling site and flow area on cardiac output measurements by Doppler echocardiography

In 40 patients cardiac output was simultaneously determined by pulsed Doppler echocardiography and thermodilution (range 4.0 to 10.2 liters/min). The sample volume was located in the center of the mitral anulus, at the tips of the mitral leaflets and in the center of the aortic anulus. Circular cross-sectional areas of the mitral anulus, aortic anulus and aortic bulbus were calculated from M-mode and two-dimensional echocardiographic diameters. The varying short axis of the elliptical mitral opening area was obtained from the diastolic leaflet separation in the M-mode, and the long axis was derived from the maximal mitral orifice area or mitral anulus diameter. Cardiac output was calculated by multiplying time-velocity integrals with the different areas and heart rate. Doppler flow measurements correlated significantly with the thermodilution method (r = 0.79 to 0.93). Flow measurements at the aortic anulus were most accurate (r = 0.93, SEE = 0.589 liter/min) if the annular area was derived from the M-mode tracing. Measurement of the anulus in the apical five chamber view yielded a significant underestimation and the area of the aortic bulbus provided an overestimation of cardiac output. Left ventricular inflow was underestimated at the mitral leaflet tips and overestimated at the mitral anulus. The accuracy of pulsed Doppler cardiac output measurements strongly depends on the assumed flow area and sampling site. Both should be determined at the same level in the inflow or outflow tract of the left ventricle. Measurement of cardiac output in the center of the aortic anulus provided the highest accuracy.

Sinus node recovery time and calculated sinoatrial conduction time in normal subjects and patients with sinus node dysfunction.

In 61 patients sinus node function was tested by programmed (sinoatrial conduction time, SACT) and overdrive atrial pacing (sinus node recovery time, SRT). In the control group (N = 20), mean sinus cycle length was 773 ± 140.2 msec, mean absolute SRT 1044 ± 215.8 msec [corrected SRT (CSRT) 270 ± 112.5 msec; mean ± SD] and calculated SACT was 82 19.2 msec. The upper limit of normal SACT was defined as 120 msec. In 41 patients with sinus node dysfunction, mean age (55 ± 14.7 years), mean spontaneous cycle length during the study (1094 ± 248.0 msec), the lowest heart rate observed (42 7.5 beats/min), maximal SRT (2110 ± 1269.1 msec), maximal CSRT (1016 1182.8 msec), and calculated SACT (126 ± 47.3 msec) were significantly longer than in the control group. Abnormalities of sinus node function, as evidenced by the degree of spontaneous bradycardia, SRT and calculated SACT were more frequent in patients with bradycardia-tachycardia syndrome or spontaneous sinoatrial block than in those exhibiting isolated sinus bradycardia. We conclude 1) that in patients with sinus node dysfunction both sinus node automaticity and sinoatrial conduction may be abnormal, and 2) that overdrive and programmed premature atrial stimulation can separate patients with sinus node dysfunction according to their clinical presentation.

Accuracy of doppler echocardiography in quantification of left to right shunts in adult patients with atrial septal defect

In previous experimental and pediatric studies, the ratio of pulmonary to systemic flow (Qp/Qs) was accurately estimated by Doppler echocardiography in various cardiac shunt lesions. The purpose of this study was to assess the accuracy of pulsed Doppler echocardiography in determining the magnitude of shunt flow in adult patients with an ostium secundum type atrial septal defect. In 32 patients with high quality echocardiograms and excellent Doppler signals, blood flow was measured in the right and left ventricular outflow tract by Doppler echocardiography. In 16 patients without heart disease, the correlation (r) between systemic (Qs) and pulmonary (Qp) blood flow was 0.96 (SEE = 0.417 liter/min, y = 1.05x - 0.21) and the mean Qp/Qs ratio was 1.01 +/- 0.09. In 16 patients with an atrial septal defect, the Qp/Qs ration measured by oximetry ranged from 1.34 to 4.61 and by pulsed Doppler echocardiography from 1.31 to 4.46 (p = NS). In these 16 patients, the correlation between the Qp/Qs ratio determined by oximetry and pulsed Doppler echocardiography was significant (r = 0.82, SEE = 0.54). In the total group of 32 patients, the correlation was stronger (r = 0.93, SEE = 0.37). Systematic differences between the invasive and noninvasive shunt calculations did not occur. Thus, in adult patients with an atrial septal defect of the secundum type and high quality echocardiograms, the magnitude of left to right shunt can be accurately assessed by pulsed Doppler echocardiography. In the absence of pulmonary hypertension, pulsed Doppler echocardiography provides precise information for the decision to undertake conservative or operative treatment.

Catheter-based therapy for hypertrophic obstructive cardiomyopathy. First in-hospital outcome analysis of the German TASH Registry.

Registerergebnisse einer Katheterbehandlung der HOCM stehen bisher nicht zur Verfügung. 1997 wurde durch die Deutsche Gesellschaft für Kardiologie das nationale, multizentrische TASH-Register (Transkoronare Ablation der Septum-Hypertrophie-Register) von HOCM-Patienten eingeführt, die mit der neuen katheterinterventionellen Methode behandelt wurden. Erstmals wird über die Akutergebnisse während des Aufenthaltes der Patienten im Krankenhaus berichtet, die in den ersten beiden Jahren nach Einführung des Registers erfasst wurden. Es wurde eine Datenbank etabliert. Die Rekrutierung erfolgte auf Intention to treat Basis und sah insgesamt 86 Variable auf drei Standard Formularen vor. Zehn Zentren nahmen teil. Schriftliche Formulardaten standen von 264 Patienten zur Verfügung aus einer Gesamtgruppe von 279 Patienten, die bis Januar 2000 gemeldet wurden. Die Patienten waren im Mittel 3,6±3,9 Jahre medikamentös behandelt worden. Die Mehrzahl der registrierten Patienten (91%) stammte aus drei Zentren. Als Stress-Methode wurden der Valsalva- Versuch oder die Belastungs- Doppler-Echokardiographie verwendet. Die Belastungs-Doppler- Echokardiographie führte zu einer signifikant stärkeren Zunahme des Druckgradienten (70,1% vs. 133,4%, p<0,01). Die Katheterintervention erfolgte in 50,8% Echokontrast gesteuert, in 49,2% der Patienten Druck-Angiographie gesteuert. Im Mittel wurden 2,8±1,3 ml Alkohol injiziert. Vor der Behandlung betrug der invasiv gemessene Gradient 60,4±38,6 mmHg in Ruhe und 142,7±46,2 mmHg postextrasystolisch. Bei Beendigung des Eingriffs war er um 75% bzw. 67% reduziert. Die maximale Aktivität der Phosphokreatin-Kinase im Serum betrug 482,5±264,4 U/L. Gravierende Komplikationen traten in 15,6% auf einschließlich einer Mortalität von 1,2% und einer Schrittmacher-Implantationsrate wegen totalen av-Blocks in 9,6%. Es kam zu einer frühzeitigen Besserung der Luftnot bei Belastung entsprechend einer Abnahme des NYHA-Stadiums von 2,8±0,7 auf 1,8±0,6 (p<0,01). Bei Patienten mit und ohne Ruhegradient zeigte sich eine gleich klinische und hämodynamische Verbesserung. Erstmals steht eine auf Registerbasis vorgenommene Datenanalyse von HOCM-Patienten zur Verfügung, die mittels der neuen Kathetermethode behandelt wurden. Sie ermöglicht einen umfassenden Überblick über klinische Daten, Technik, periinterventionelle Ergebnisse und Komplikationen bei einer großen Zahl von Patienten. Die Ergebnisse tragen wesentlich zur kritischen Beurteilung und Validierung der neuen Methode bei. Sie unterstützen bisherige Ergebnisse, nach denen die Katheterbehandlung der HOCM als Alternative zur herzchirurgischen Behandlung eine neue therapeutische Option bei sehr symptomatischen HOCM-Patienten darstellt. Sie erwies sich sowohl bei Patienten mit als auch bei Patienten ohne intraventrikulärem Druckgradienten in Ruhe als effektiv. Registry results of the new catheter-based method in the treatment for HOCM are missing so far. In 1997, the Transcoronary Ablation of Septal Hypertrophy Registry (TASH Registry) was established by the German Cardiac Society (GCS) as a multicenter, national registry of patients with HOCM undergoing the new catheter interventional therapy. This is the report of the in-hospital outcome of patients who underwent the procedure during the first two years of data collection in the registry. Information was based on three standard forms for each patient, with a total of 86 variables. Information was collected on an “intention to treat” basis. The TASH Registry includes the establishment of a data base in the data collecting center. Ten centers participated. Enrollment forms were received for 264 patients out of 279 patients registered up to January 2000. There was a history of medical treatment of 3.6±3.9 years. The vast majority of patients (91%) were treated in three centers. The Vasalva maneuver and the exercise Doppler echocardiography were used for noninvasive stress testing. Exercise Doppler echocardiography induced a significantly higher augmentation of the baseline gradient (70.1% vs 133.4%; p<0.01). The echo-contrast guided technique was used for the intervention in 50.8% and the pressureangiography guided technique in 49.2%. On the average 2.8±1.3 ml of alcohol were injected. Before the procedure, the gradient measured by catheterization was 60.4±38.6 mmHg at baseline and 142.7±46.2 mmHg following the extrasystolic beat. At the end of the session it was reduced significantly by 75% and 67%. The peak phosphocreatine kinase activity was 482.5±246.4 U/L. Major complications occurred in 15.6% including a mortality rate of 1.2% and a permanent pacemaker implantation rate because of total heart block in 9.6%. There was an early in-hospital improvement of dyspnoe corresponding to a significant decrease of NYHA functional class from 2.8±0.7 to 1.8±0.6 (p<0.001). Similar hemodynamic and clinical benefit was found in patients with and without resting gradient at baseline. This analysis for the first time gives a comprehensive overview of clinical characteristics, technique, procedural data, in-hospital outcome and complications in a large number of patients with HOCM who were treated by the new catheter-based method and prospectively enrolled in a registry. The results contribute considerably to critical evaluation and validation of the new technique. This analysis supports the catheter-based method to constitute a new therapeutic option for very symptomatic patients, to be effective both in patients with and without intraventricular pressure gradient at rest and to be an alternative to surgical treatment, as has been stated recently.

β3-Adrenergic regulation of an ion channel in the heart—inhibition of the slow delayed rectifier potassium current IKs in guinea pig ventricular myocytes

Objectives: I Ks, the slow component of the delayed rectifier potassium current, underlies a strong β-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in I Ks. Recent work has pointed to an opposing biological effect of β1- and β3-adrenoceptors in the heart. However the role of these subtypes in the regulation of cardiac ion channel function is unknown. Methods: We investigated the effects of β1- and β3-adrenoceptor modulation on I Ks in guinea-pig ventricular myocytes, using patch-clamp techniques. Results: Superfusion with 100 nmol/l isoproterenol increased the step current amplitude by 81.3±8.0%. In contrast, after block of β1- (1 μmol/l atenolol) and β2-receptors (1 μmol/l ICI118,551), isoproterenol induced a reduction of the step current amplitude by 34.3±3.5%. The β3-selective agonist BRL37344 significantly reduced the I Ks step current at +70 mV in a concentration-dependent manner (IC50: 5.01 nmol/l). In the presence of bupranolol (β1-, β2- and β3-adrenoceptor antagonist), the effect of BRL37344 was markedly attenuated, from 27.3±5.6% (100 nmol/l BRL37344 alone) to 4.0±1.3% (100 nmol/l BRL37344+1 μmol/l bupranolol). BRL37344 (100 μmol/) did not alter current amplitudes of KvLQT1/minK expressed in CHO cells or in Xenopus oocytes, excluding a direct effect of BRL37344 on the channel. 1 μmol/l BRL37344 mildly prolonged action potentials in guinea pig ventricle (APD90:+7.8%) Conclusions: We have demonstrated a functional coupling between the β3-adrenoceptor and ion channel function in the mammalian heart. Our findings point to a potential role for β3-adrenoceptors in cardiac electrophysiology and pathophysiology.

Catheter-based septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: follow-up results of the TASH-registry of the German Cardiac Society.

Im Herbst 1997 richtete die Deutsche Gesellschaft für Kardiologie ein bundesweites Register ein, das den Hospital- und mittelfristigen Verlauf bei mittels perkutaner Septumablation behandelten Patienten (Pat.) mit hypertropher obstruktiver Kardiomyopathie (HOCM) erfassen sollte. Die Analyse des Hospitalverlaufs liegt inzwischen vor. Wir berichten jetzt über den mittelfristigen Verlauf (3–6 Monate) der bis September 1999 eingeschlossenen Patienten. Rückmeldungen lagen für 222 von 242 initial erfassten Pat. vor (92%). Im Follow-up-Zeitraum (4,9±2,3 Monate) verstarben 3 weitere Pat. (Hospitalmortalität: 3 Pat. (1,2%)). Über einen zufriedenstellenden Effekt der Intervention berichteten 195 Pat. (88%). Die akut erreichte Senkung des LVOT-Gradienten (LVOTG) von 57±31 auf 25±25 mmHg in Ruhe und von 107±53 auf 49±40 mmHg unter Provokation war nach 3–6 Monaten weiter akzentuiert (auf 20±21 mmHg in Ruhe bzw. 44±40 mmHg unter Provokation, p sämtlich <0,001), was für ein zeitabhängiges lokales Remodeling im Bereich der septalen Zielregion spricht. LA-Diameter (von 46±8 auf 44±7 mm), Septumdicke (von 20±5 auf 15±5 mm) und Dyspnoe, klassifiziert nach NYHA (von 2,8±0,7 auf 1,7±0,7) nahmen ebenfalls ab (p jew. <0,001). Interventionen unter Einschluss der intra-prozeduralen Echokardiographie sowie solche mit angiographisch/ durch Druckmessung erfolgender Steuerung waren hinsichtlich der klinischen Besserung und der invasiven Resultate vergleichbar. Im mittelfristigen Verlauf nach Kathetertherapie, sowohl kontrastechokardiographisch wie auch per Druckmessung/fluoroskopisch gesteuert, bestätigen sich die positiven Akutergebnisse mit einem weiteren Absinken des LVOTG. LA-Last und Septumdicke nehmen ab, die körperliche Belastbarkeit nimmt weiter zu. In late 1997, the German Cardiac Society set up a multicenter registry to evaluate the acute and mid-term course of all patients (pts.) treated with septal ablation for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). An analysis of the acute results has already been published. We now report on the mid-term course (3–6 months) of 242 pts. registered through September 1999. Follow-up was 92% complete (n=222). During follow-up (mean: 4.9±2.3 months), an additional 3 pts. died (in-hospital mortality: 3 pts.). A satisfactory clinical effect was reported by 195 pts. (88%); 27 pts. (12%) remained in NYHA classes III and IV. Overall symptomatic improvement (NYHA class: from 2.8±0.7 to 1.7±0.7) paralleled the outflow gradient (LVOTG) reduction which was further accentuated as compared with the acute result (Doppler measurement at rest: from 57±31 to 25±25 mmHg to 20±21 mmHg; with provocation: from 107±53 to 49±40, to 44±40 mmHg, p<0.001, resp.). Left atrial (LA) diameter (from 46±8 to 44±7 mm) and septal thickness (from 20±5 to 15±5 mm; p<0.001, resp.) were also reduced. Comparing the methods for target vessel selection (i.e., with contrast echo monitoring vs pressurefluoroscopy guidance), at followup clinical improvement and hemodynamic measurements were comparable. Clinical success can be achieved by septal ablation, both with the echocontrast guided and gradient-fluoroscopy guided method, in 88% of highly symptomatic HOCM pts. At mid-term follow-up, symptoms, left atrial size and septal thickness are reduced, and outflow gradients are further improved as compared to the acute result.

Long-term experience with subcutaneous ICD leads: a comparison among three different types of subcutaneous leads.

ICDs provide protection against sudden cardiac death in patients with life‐threatening arrhythmias. Nevertheless, efficacy of defibrillation remains an important issue to guarantee the future safety of patients who receive an ICD. There is a significant number of patients who need an additional subcutaneous lead to obtain a defibrillation safety margin of at least 10 J between the maximum output of the ICD and the energy needed for ventricular defibrillation. However, few data exists about the long‐term performance of different types of subcutaneous leads. Therefore, the aim of this study was to analyze the long‐term experience with three different types of subcutaneous leads. The study included 132 patients (109 men, 23 women; mean age 59.8 years [SD ± 10.7 years]). All of them received a subcutaneous lead in addition to a single chamber or dual chamber ICD between October 1990 and April 2002. Two patients received a second subcutaneous lead after the first lead had been removed so that a total of 134 subcutaneous leads were evaluated. Inclusion criteria for the implantation of an additional subcutaneous lead were (1) unsuccessful ventricular defibrillation at implant without a subcutaneous lead, (2) insufficient safety margin (< 10 J) between the maximum output of the ICD and the energy needed for ventricular defibrillation, or (3) clinical evaluation of a new subcutaneous lead (Medtronic 13014). There were no significant differences between the three study groups with regard to age, sex, underlying cardiac disease, left ventricular ejection fraction, NYHA class assessment and clinical arrhythmia. The results of the DFT testing during follow‐up (prehospital discharge test and 1 and 3 years) were compared to the baseline value obtained during the implantation procedure. All lead related complications were analyzed. Eighty‐two single element subcutaneous array electrodes (SQ‐A1), 31 subcutaneous three‐finger electrodes (SQ‐A3), and 21 subcutaneous patch electrodes (SQ‐P) were implanted during the study period. The median follow‐up was 1,499 days (25th percentile: 798 days, 75th percentile: 1,976 days) in the SQ‐A1 group, 2,209 days (25th percentile: 1,242 days, 75th percentile: 2,710 days) in the SQ‐A3 group, and 1,419 days (25th percentile: 787 days, 75th percentile: 2,838 days) in the SQ‐P group. None of the three groups had a significant change of the DFT during follow‐up compared to baseline. Major complications occurred in six (7.3%) patients in group SQ‐A1 and in two (9.5%) patients in group SQ‐P. There were no major complications in group SQ‐A3. Kaplan‐Meier curves analyzing freedom from subcutaneous lead related complications did not show a significant difference between the three study groups (P = 0.16). SQ‐A1, SQ‐A3, and SQ‐P leads provide stable DFTs during long‐term follow‐up. Major complications are rare. However, a careful follow‐up including chest radiographs at regular intervals is needed to detect potentially fatal complications like lead fractures.