Jörg Neuzner

Efficacy of everolimus eluting stent implantation in patients with calcified coronary culprit lesions: two-year angiographic and three-year clinical results from the SPIRIT II study

Background: Little is known about the impact of treatment with drug‐eluting stents (DES) on calcified coronary lesions. This analysis sought to assess the safety and efficacy of the XIENCE V everolimus‐eluting stent (EES) in patients with calcified or noncalcified culprit lesions. Methods: The study population consisted of 212 patients with 247 lesions, who were treated with EES alone. Target lesions were angiographically classified as none/mild, moderate, or severe grades of calcification. The population was divided into two groups: those with at least one target lesion moderately or severely calcified (the calcified group: 68 patients with 75 calcified lesions) and those with all target lesions having mild or no calcification (the noncalcified group: 144 patients). Six‐month and 2‐year angiographic follow‐up and clinical follow‐up up to 3 years were completed. Results: The baseline characteristics were not significantly different between both groups. When compared with the noncalcified group, the calcified group had significantly higher rates of 6‐month in‐stent angiographic binary restenosis (ABR, 4.3% vs. 0%, P = 0.03) and ischemia‐driven target lesion revascularization (ID‐TLR, 5.9% vs. 0%, P = 0.01), resulting in numerically higher major cardiac adverse events (MACE, 5.9% vs. 1.4%, P = 0.09). At 2 years, when compared with the noncalcified group, the calcified group presented higher in‐stent ABR (7.4% vs. 0%, P = 0.08) and ID‐TLR (7.8% vs. 1.5%, P = 0.03), resulting in numerically higher MACE (10.9% vs. 4.4%, P = 0.12). At 3 years, ID‐TLR tended to be higher in the calcified group than in the noncalcified group (8.6% vs. 2.4%, P = 0.11), resulting in numerically higher MACE (12.1% vs. 4.7%, P = 0.12). Conclusions: The MACE rates in patients treated with EES for calcified lesions were higher than in those for noncalcified lesions, but remained lower than the results of previously reported stent studies. EES implantation in patients with calcified culprit lesions was safe and associated with favorable reduction of restenosis and repeat revascularization.

Implantable Cardioverter Defibrillator: Effect on Survival

On the occasion of William Harveys tercentenary day of death in 1957, Claude S. Beck published papers dealing with differences in myocardial oxygenation and their present and future surgical treatment. He provocatively postulated that by such oxygen differences, hearts otherwise too good to die succumbed to electrical self-execution, thus killing the patients.^-^ In 1957, it was only by chance that such a victim survived, while survival from cardiocirculatory arrest of arrhythmic origin is no longer a rare event. If the estimation that about 50% of all cardiac deaths occur suddenly is approximately correct, then we are faced with a considerable number of hearts too good to die.^ If treatment with an implantable cardioverter defibrillator (ICD) is considered to be effective in saving lives, then knowledge of the number of patients in need of such a device could shed light on the otherwise obscure number.

A Dose-response Study of Intravenous Enoximone in Congestive-heart-failure

Previous clinical studies with intravenous enoximone have used cumulative dosing to quantify enoximones hemodynamic effects. The magnitude and duration of the hemodynamic effects of single intravenous doses of enoximone were evaluated in patients with congestive heart failure. Sixty patients, who were in New York Heart Association functional classes III and IV, received single intravenous doses of enoximone, either 0.25 (12 patients), 0.5 (13 patients), 1 (14 patients), 1.5 (10 patients) or 2 mg/kg (11 patients). Cardiac index was increased by 20% with the 0.25 mg/kg dose and by 48% and 42% with the 1.5 and 2 mg/kg doses, respectively. These increases were statistically significant (Students paired t test with Bonferronis correction, p less than 0.007) for 1 hour after 0.25 and 0.5 mg/kg, for 2 hours after 1 mg/kg and for 4 hours after 1.5 and 2 mg/kg. Enoximone also reduced pulmonary artery diastolic pressure by 19% with 0.25 mg/kg and by 29% with 2 mg/kg. The duration of effect varied from 1 hour with 0.25 mg/kg to 4 hours with 2 mg/kg. Enoximone produced no consistent or dose-related effects on heart rate or blood pressure. Eighteen adverse reactions were reported by 15 patients, of which 11 were minor and transient (vein pain, flushes, nausea). In 5 patients ventricular or supraventricular arrhythmias were observed, including nonsustained ventricular tachycardia and extrasystoles; 3 of these patients had evidence of arrhythmias before enoximone. Laboratory studies before and after treatment showed no drug-related effects. Dose-related effects on the magnitude and duration of hemodynamic responses to intravenous enoximone were evident within the dose range of 0.25 to 2 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Tedisamil (KC 8857) is a new specific bradycardic drug: does it also influence myocardial contractility? Analysis by the conductance (volume) technique in coronary artery disease.

To determine whether inotropism influences the bradycardic action of tedisamil, hemodynamic assessment was performed in 13 patients with ischemic coronary artery disease including analysis of end-systolic pressure-volume relationships after an infusion of tedisamil, 0.3 mg/kg, at rest, and during paced tachycardia stress. Slope Emax fell by 14% at rest (13 patients) and by 10% during tachycardia (6/13 patients), whereas loops of end-systolic pressure-volume relationships moved rightward; all parameter changes indicated a lack of significant inotropism loss with tedisamil (p > 0.05). Although the mean heart rate decreased from 77.5 to 64.7 beats/min and QTc duration increased by 14% (p < 0.05), filling pressure and dp/dtmin remained unchanged and vascular resistance increased by 30%. Parameters of left ventricular pump function (ejection fraction, stroke volume, left ventricular efficiency) decreased slightly (between 3% and 13%), whereas left ventricular volumes increased (end-diastolic volume by 6%, end-systolic volume by 23%). The respective parameter changes during tachycardia were comparable in tendency, and angina could no longer be induced during postdrug pacing stress. We concluded that the bradycardic effects of tedisamil are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion, whereas the postdrug anginal threshold appears elevated. Thus tedisamil can be used safely in ischemic coronary artery disease.

Hemodynamic, antiischemic, and neurohumoral effects of enoximone in patients with coronary artery disease.

To evaluate the risk of ischemia in 17 patients with significant coronary artery disease, the influence of enoximone was analyzed under the following conditions: (1) at rest (RC) and during exercise (ExC) under control conditions and (2) at rest (RE) and during exercise (ExE) after administration of enoximone (0.75 mg/kg, intravenously). During ExC all patients had ischemia (angina, and ST segment alterations); metabolic markers of ischemia (MMI) increased, as did the mean pulmonary artery pressure, from 19 to 41 mm Hg. However, during ExE ischemia was abolished (no angina, decrease in mean pulmonary artery pressure to 24 mm Hg, and improvement in MMI) and there was some improvement in left ventricular pump function, whereas pre- and afterload decreased (pulmonary artery pressure by 40%, systemic vascular resistance by 10%), and heart rate, arterial pressure, and myocardial oxygen consumption (MVO2) were all unchanged (p greater than 0.05). Comparative hemodynamics at RE vs RC showed a decrease in pulmonary artery pressure (by 25%) and pulmonary vascular resistance (by 19%) and an increase in heart rate (by 11%), whereas arterial pressure and MVO2 were unchanged (p greater than 0.05). Enoximone did not induce changes in plasma catecholamine, prostaglandin, or thromboxane levels (p greater than 0.05), whereas the atrial natriuretic factor decreased (by 15%), probably because of unloading of the atria during exercise. We concluded that enoximone induces beneficial hemodynamic effects in coronary artery disease without causing ischemia, probably by enhancing myocardial contractility, vasodilation, and improved diastolic properties.

Systemic exposure of everolimus after stent implantation: A pharmacokinetic study

OBJECTIVES We evaluated the pharmacokinetics of the eluted everolimus by assessing systemic drug release and distribution of everolimus-eluting stents. BACKGROUND Drugs eluted by a coronary stent might cause adverse events such as tumors, infections, or noncardiac death. The systemic exposure of the drugs is unknown because there are only limited data about pharmacokinetics of drug-eluting stents in humans. METHODS Venous blood samples in a subset of 39 patients were drawn just before implantation of the first stent (baseline, 0-minute time point) and at 10 and 30 minutes and 1, 2, 4, 6, 12, 24, 36, 48, 72, 168, and 720 hours (30 days) after completion of implantation of the last stent. Whole blood concentrations of everolimus were determined using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method. RESULTS The total dose of everolimus received by the patients ranged from 53 to 588 microg. The last time point up to which whole blood concentrations could be quantified ranged per patient from 4 to 720 hours after implantation of the last stent. Across all dose levels, individual T(max) values ranged from 0.13 and 2.17 hours; individual C(max) ranged from 0.14 to 2.79 ng/mL. CONCLUSION This study confirms the limited exposure to the systemic circulation of the eluted drug with the use of the XIENCE V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, CA). Therefore, a systemic cause of adverse events is unlikely.

Radiofrequency Catheter Ablation of a Concealed Accessory Atrioventricular Pathway After Heart Transplantation

Three months after orthotopic cardiac transplantation, a 46‐year‐old man developed paroxysmal supraventricular tachycardia. Electrophysiological investigation of the arrhythmia led to the diagnosis of an atrioventricular reentrant tachycardia involving a left lateral concealed accessory pathway. When antiarrhythmic drugs failed to suppress the arrhythmia, radiofrequency catheter ablation of the accessory pathway was performed without complication.

Antiischemic and hemodynamic effects of an oral single dose of 150 mg of the phosphodiesterase inhibitor enoximone in patients with coronary artery disease—relation to plasma concentration

SummaryThe hemodynamic and antiischemic effects of a 150-mg single oral dose of the PDE inhibitor enoximone were correlated with the plasma levels of enoximone and its sulfoxide metabolite. Twenty-one patients with angiographically documented coronary artery disease were investigated by exercise testing 1 and 2 hours after drug administration. The control group consisted of 15 patients with proven coronary artery disease and stable reproducible angina pectoris on exercise. The enoximone group included 14 responders with therapeutic plasma concentrations 2 hours after drug intake and significantly reduced mean pulmonary artery pressures on exercise (from 42.4 ± 8.6 to 30.9 ± 11.2 mmHg, p < 0.05). Compared to basal exercise values, responders showed a reduced ST-segment depression by 1 hour after drug intake (2.1 ± 1.2 vs. 1.3 ± 3 mm, p < 0.05) and minimal values after 2 hours (0.9 ± 1.0 mm, p < 0.01) at comparable workloads. There were no significant changes in heart rate, blood pressure, cardiac output, and systemic vascular resistance. No significant improvement in the hemodynamic parameters and ST-segment depression was found in nonresponders with plasma concentrations below 100 ng/ml and 500 ng/ml for enoximone and its metabolite, respectively. In summary, oral administration of enoximone in patients with coronary artery disease led to favorable acute hemodynamic and antiischemic effects at sufficiently high plasma levels of enoximone and its sulfoxide metabolite.

Intracardiac Emergency Defibrillation for Refractory Ventricular Fibrillation During Implantation of Cardioverter Defibrillators with Nonthoracotomy Lead Systems

Implantable cardioverter defibrillators (ICDs) are being implanted in increasing numbers. At inlraoperative defibrillation threshold tests refractory ventricular fibrillation (VF) requiring emergency open chest resuscitation is a major concern during impiantation of nonthoracotomy ICD lead systems. A new method of high energy endocardial/extrathoracic defibrillotion via the implanted ICD transvenous defibrillation electrode (TDE) was used to terminate refractory VF. During implantation of ICD with TDE in 20 patients refractory VF occurred in two patients. The arrhythmia was terminated with endocardial/extrathoracic defibrillation in both cases, and no complications were observed.