Christina Unterberg

Low-molecular-weight heparin reduces neointimal proliferation after coronary stent implantation in hypercholesterolemic minipigs.

BackgroundIntracoronary stents have been suggested as a method of reducing the restenosis rate after balloon angioplasty. Proliferation of vascular smooth muscle cells is a major contributing factor to the restenosis process. Heparin and some of its derivatives have been shown to inhibit smooth muscle cell proliferation. We investigated the effect of low-molecular-weight heparin on the proliferative response after implantation of a balloon-expandable tantalum stent in previously deendothelialized coronary artery segments of hypercholesterolemic minipigs. Methods and ResultsMinipigs were fed a diet containing 2% cholesterol, starting 1 month before balloon denudation of the endothelium in a coronary artery. One month later, a stent was implanted at this site. Animals were killed after 4 weeks (group 1, n = 6) or 3 months (group 2, n = 6). Animals in group 3 (n = 6), also followed for 4 weeks after stenting, received subcutaneous low-molecular-weight heparin at a dose of 200–300 units/kg anti-factor Xa activity per day in addition to the chronic acetylsalicylic acid (100 mg/day) also administered to groups 1 and 2. Eighteen of 22 animals survived to the end of the study. Angiography revealed patent stents in all surviving animals. In group 1, histological analysis showed extensive neointimal proliferation around stent struts. Maximal neointimal thickness seen in group 1 averaged 0.93±0.11 mm, was lower after 3 months (0.8±0.14 mm) in group 2, but was significantly reduced (0.44±0.18 mm, p < 0.01) in group 3. ConclusionsThese data show a significant reduction of the neointimal proliferative response to coronary stent implantation by low-molecular-weight heparin.

Reduced acute thrombus formation results in decreased neointimal proliferation after coronary angioplasty

OBJECTIVES We tested the hypothesis that reduced acute platelet deposition after angioplasty results in reduced late neointimal proliferation. BACKGROUND Platelet-mediated mechanisms contribute to smooth muscle cell proliferation and migration. METHODS Indium-111-labeled platelets were injected 16 h before coronary stent angioplasty in 10 Göttinger minipigs: group 1 (n = 5) = heparin (100-U/kg bolus) before angioplasty; group 2 (n = 5) = recombinant hirudin (CGP 39393, 1.0-mg/kg body weight bolus intravenously), followed by subcutaneous doses of 6 to 10 mg/kg every 8 h. Furthermore, stent angioplasty was performed in coronary arteries of 16 minipigs: group 3 (n = 5, nine stents) = 100 U/kg heparin only; group 4 (n = 5, 10 stents) = 1-mg/kg bolus hirudin before and 45 min after angioplasty; group 5 (n = 6, 11 stents) = hirudin (1-mg/kg intravenous bolus) before and 45 min after angioplasty, followed by 6 to 10 mg/kg subcutaneously every 8 h. RESULTS In segments with deep arterial injury, the number of platelets/angioplasty segment in group 2 after 72 h (mean 21, range 9.7 to 39.7 x 10(6)) was significantly less than that in group 1 (mean 375, range 72 to 787 x 10(6)). Morphometric analysis after 4 weeks showed no difference between groups in degree of vessel wall injury. Mean (+/- SD) neointimal thickness was 0.70 +/- 0.06 mm in group 3 and was significantly reduced in both group 4 (0.46 +/- 0.11 mm) and group 5 (0.48 +/- 0.21 mm). CONCLUSIONS The direct thrombin inhibitor hirudin significantly reduces platelet deposition up to 72 h after coronary stent angioplasty. A hirudin bolus alone as well as continued subcutaneous administration for 14 days substantially reduced neointimal proliferation compared with heparin 4 weeks after coronary stent angioplasty in minipigs.

Intrathoracic impedance monitoring to detect chronic heart failure deterioration: Relationship to changes in NT-proBNP

An alert algorithm, based on intrathoracic impedance monitoring, has been incorporated into a cardiac resynchronisation device (CRT) to detect pulmonary fluid accumulation, and to audibly alert patients to decompensating chronic heart failure (CHF).

Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.

OBJECTIVES The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting. BACKGROUND Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices. METHODS In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animals were pretreated with aspirin (250 mg intravenously). RESULTS Activated partial thromboplastin time was prolonged to > 1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stents averaged 116.2 (range 22 to 522) x 10(6) in group 1, 64.3 (range 11 to 169) x 10(6) in group 2 and 19.7 (range 9 to 38) x 10(6) in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition, associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudin-treated animals. CONCLUSIONS Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.

Incremental programming of atrial anti-tachycardia pacing therapies in bradycardia-indicated patients: effects on therapy efficacy and atrial tachyarrhythmia burden

AIMS Efficacy of pace-termination of atrial arrhythmias (ATP) may depend on atrial cycle length and regularity. Whether device programming of ATP therapies can improve ATP efficacy and alter atrial tachyarrhythmia burden is unknown. METHODS AND RESULTS ATP efficacy was evaluated in 61 patients (39 males; 66 +/- 10 years) with a standard indication for pacing, 95% with a history of AT/AF. Each patient was implanted with a novel DDDRP pacemaker capable of delivering ATP therapy. ATP efficacy and AT/AF frequency and burden were compared within each patient during a period of nominal ATP programming (NP) followed by a period of aggressive incremental programming (IP). Adjusted ATP-termination efficacy was higher during IP than during NP (54.8% vs 37.9%, P < 0.05). No differences in AT/AF frequency (3.3 +/- 5.9 vs 3.2 +/- 6.9 day(-1)) or burden (18 +/- 28% vs 18 +/- 29%) were observed comparing NP with IP. The majority of episodes during both the NP (81%) and IP (77%) periods terminated within 10 min. Episodes lasting 24 h or more accounted for only 0.4% of the episodes in both groups. but accounted for 38% of the average burden during NP and 51% during IP. CONCLUSIONS Device programming of ATP therapies can influence the number of treated episodes and the efficacy of ATP therapies although arrhythmic frequency and burden may not change. Total atrial arrhythmia burden is disproportionately influenced by long (>24 h) episodes.

Restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions

In an open clinical study, a xenon-chloride excimer laser was used for angioplasty of coronary stenoses (n = 48) and chronic total occlusions (n = 56) in 104 patients. Multifiber catheters (4.0F to 5.5F) transmitted 37 to 120 mjoules/mm2 of fiber surface. Excimer laser angioplasty was successful in 43 patients with a stenosis (89%), followed by percutaneous transluminal coronary angioplasty in 21 patients (49%) to reduce the stenosis to less than 50% luminal narrowing. In 39 patients (70%) with a chronic occlusion (age 1 to 14 months), recanalization by means of excimer laser angioplasty was successful, with subsequent percutaneous transluminal coronary angioplasty performed in 23 patients. Major complications included one perforation, one acute occlusion, and two severe dissections. Six-month angiographic follow-up examinations after successful angioplasty were completed in 40 patients (98%) with stenoses and 34 (94%) with occlusions. Restenosis (greater than 20% decrease in luminal diameter) occurred in 13 patients (33%) with stenoses and in 16 patients (47%) after angioplasty of a chronic occlusion. These long-term results indicate that restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions is similar to reported results of conventional balloon angioplasty.

Acute effects of the new angiotensin converting enzyme inhibitor ramipril on hemodynamics and carotid sinus baroreflex activity in congestive heart failure.

The hemodynamic effects of a single dose of 5 mg of ramipril, a new angiotensin converting enzyme inhibitor, were investigated in 10 patients with chronic congestive heart failure. Arterial blood pressure and total peripheral resistance were decreased by approximately 12% without causing reflex tachycardia. A highly significant decrease occurred in mean pulmonary artery and pulmonary capillary wedge pressures. These hemodynamic changes were equally pronounced at rest and during exercise on a bicycle ergometer; the effect was of the same magnitude 5 and 24 hours after medication. Angiotensin converting enzyme activity in plasma was nearly completely inhibited after 5 hours and remained at about 12% of control after 24 hours. Cardiac index, which was normal before treatment, remained unaffected. Thus, ramipril induced a balanced reduction of left ventricular pre- and afterload. The activity of the carotid sinus baroreflex was investigated in 8 of the patients using the neck suction technique before and 24 hours after ramipril. The reflex bradycardia during stimulation of the baroreceptors was significantly increased by ramipril, whereas the decrease in blood pressure remained essentially unaffected. Ramipril induced a selective sensitization of the parasympathetic baroreceptor heart rate reflex without influencing the sympathetically mediated peripheral vasodilatation. This effect may be responsible for the lack of reflex tachycardia in spite of the decrease in blood pressure.

Inhibition of Bradycardia Pacing and Detection of Ventricular Fibrillation Due to Far‐Field Atrial Sensing in a Triple Chamber Implantable

VOLLMANN, D., et al.: Inhibition of Bradycardia Pacing and Detection of Ventricular Fibrillation Due to Far‐Field Atrial Sensing in a Triple Chamber Implantable Cardioverter Defibrillator. Oversensing of intracardiac signals or myopotentials may cause inappropriate ICD therapy. Reports on far‐field sensing of atrial signals are rare, and inappropriate ICD therapy due to oversensing of atrial fibrillation has not yet been described. This report presents a patient with a triple chamber ICD and a history of His‐bundle ablation who experienced asystolic ventricular pauses and inappropriate detection of ventricular fibrillation due to far‐field oversensing of atrial fibrillation. Several factors contributed to the complication, which resolved after reduction of the ventricular sensitivity.

Long‐Term Clinical Experience with the EGM Width Detection Criterion for Differentiation of Supraventricular and Ventricular Tachycardia in Patients with Implantable Cardioverter Defibrillators

UNTERBERG, C., et al.: Long‐Term Clinical Experience with the EGM Width Detection Criterion for Differentiation of Supraventricular and Ventricular Tachycardia in Patients with Implantable Cardioverter Defibrillators. Inappropriate therapy by ICDs due to SVTs is an important problem. A third generation ICD with a new detection criterion (“EGM width criterion”) for differentiation of SVTs and VTs by measuring the width of the intracardiac EGM was studied in 47 patients. A wide EGM was defined as the longest measured EGM plus 4–12 ms (programmed as EGM width threshold). EGM width detection function was programmed to the “Passive” mode so that no therapy was withheld. During a follow‐up of 29.9 ± 8.3 (12–45) months, 489 spontaneous episodes were analyzed. SVTs occurred in ten patients with 305 episodes; 301 were correctly classified by use of the new detection criterion. In four patients four episodes were incorrectly detected as wide QRS tachycardias. Thus specificity for SVT was 98.7% (on a per episode basis) and 60% on a per patient basis. Of 184 VTs in 23 patients, 118 episodes were correctly classified (19 patients), however, in 4 patients 66 VTs were falsely detected as SVTs, 62 (94%) of which occurred in 1 patient with complete left BBB and continuously increasing QRS width in 12‐lead surface ECGs. Overall sensitivity (on a per episode basis) for VT detection was 64.1% and 96.7% in patients with stable width of the QRS complex in a 12‐lead surface ECG. These data show that this criterion is not superior to data on rate dependent detection criteria and furthermore not applicable in patients with complete BBB.

The total right/left-volume index: a new and simplified cardiac magnetic resonance measure to evaluate the severity of Ebstein anomaly of the tricuspid valve: a comparison with heart failure markers from various modalities.

Background—The classification of clinical severity of Ebstein anomaly still remains a challenge. The aim of this study was to focus on the interaction of the pathologically altered right heart with the anatomically—supposedly—normal left heart and to derive from cardiac magnetic resonance (CMR) a simple imaging measure for the clinical severity of Ebstein anomaly. Methods and Results—Twenty-five patients at a mean age of 26±14 years with unrepaired Ebstein anomaly were examined in a prospective study. Disease severity was classified using CMR volumes and functional measurements in comparison with heart failure markers from clinical data, ECG, laboratory and cardiopulmonary exercise testing, and echocardiography. All examinations were completed within 24 hours. A total right/left-volume index was defined from end-diastolic volume measurements in CMR: total right/left-volume index=(RA+aRV+fRV)/(LA+LV). Mean total right/left-volume index was 2.6±1.7 (normal values: 1.1±0.1). This new total right/left-volume index correlated with almost all clinically used biomarkers of heart failure: brain natriuretic peptide (r=0.691; P=0.0003), QRS (r=0.432; P=0.039), peak oxygen consumption/kg (r=−0.479; P=0.024), ventilatory response to carbon dioxide production at anaerobic threshold (r=0.426; P=0.048), the severity of tricuspid regurgitation (r=0.692; P=0.009), tricuspid valve offset (r=0.583; P=0.004), and tricuspid annular plane systolic excursion (r=0.554; P=0.006). Previously described severity indices ([RA+aRV]/[fRV+LA+LV]) and fRV/LV end-diastolic volume corresponded only to some parameters. Conclusions—In patients with Ebstein anomaly, the easily acquired index of right-sided to left-sided heart volumes from CMR correlated well with established heart failure markers. Our data suggest that the total right/left-volume index should be used as a new and simplified CMR measure, allowing more accurate assessment of disease severity than previously described scoring systems.